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  • 1. Adams, Charleen
    et al.
    Richmond, Rebecca C
    Santos Ferreira, Diana L
    Spiller, Wes
    Tan, Vanessa Y
    Zheng, Jie
    Wurtz, Peter
    Donovan, Jenny L
    Hamdy, Freddie C
    Neal, David E
    Lane, J Athene
    Davey Smith, George
    Relton, Caroline L
    Eeles, Rosalind A
    Henderson, Brian E
    Haiman, Christopher A
    Kote-Jarai, Zsofia
    Schumacher, Fredrick R
    Amin Al Olama, Ali
    Benlloch, Sara
    Muir, Kenneth
    Berndt, Sonja I
    Conti, David V
    Wiklund, Fredrik
    Chanock, Stephen J
    Gapstur, Susan M
    Stevens, Victoria L
    Tangen, Catherine M
    Batra, Jyotsna
    Clements, Judith A
    Grönberg, Henrik
    Pashayan, Nora
    Schleutker, Johanna
    Albanes, Demetrius
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    West, Catharine M L
    Mucci, Lorelei A
    Cancel-Tassin, Geraldine
    Koutros, Stella
    Sørensen, Karina D
    Maehle, Lovise
    Travis, Ruth C
    Hamilton, Robert
    Ingles, Sue Ann
    Rosenstein, Barry S
    Lu, Yong-Jie
    Giles, Graham G
    Kibel, Adam S
    Vega, Ana
    Kogevinas, Manolis
    Penney, Kathryn L
    Park, Jong Y
    Stanford, Janet L
    Cybulski, Cezary
    Nordestgaard, Borge G
    Brenner, Hermann
    Maier, Christiane
    Kim, Jeri
    John, Esther M
    Teixeira, Manuel R
    Neuhausen, Susan L
    DeRuyck, Kim
    Razack, Azad
    Newcomb, Lisa F
    Lessel, Davor
    Kaneva, Radka P
    Usmani, Nawaid
    Claessens, Frank
    Townsend, Paul
    Gago Dominguez, Manuela
    Roobol, Monique J
    Menegaux, Florence
    Khaw, Kay-Tee
    Cannon-Albright, Lisa A
    Pandha, Hardev
    Thibodeau, Stephen N
    Martin, Richard M
    Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study.2018In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, article id cebp.0079.2018Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

    MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

    CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

    IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

  • 2.
    Ahlin, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Zhou, Wenjing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Holmqvist, Marit
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Jirström, Karin
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Cyclin A is a proliferative marker with good prognostic value in node-negative breast cancer2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 9, p. 2501-2506Article in journal (Refereed)
    Abstract [en]

    Background: Proliferative markers are not recommended as prognostic   factors for clinical use in breast cancer due to lack of   standardization in methodology. However, proliferation is driving   several gene expression signatures emphasizing the need for a reliable   proliferative marker IF or clinical use. Studies suggest that cyclin A   is a prognostic marker with satisfying reproducibility. We investigated   cyclin A as a prognostic marker in node-negative breast cancer using   previously defined cutoff values.   Patients and Methods: In a case-control study, we defined 190 women who   died from breast cancer as cases and 190 women alive at the time for   the corresponding case's death as controls. Inclusion criteria were   tumor size <= 50 mm, no lymph node metastases and no adjuvant   chemotherapy. Tumor tissues were immunostained for cyclin A using   commercially available antibodies.   Results: We found a statistically significant association between   expression of cyclin A and breast cancer death in a univariate model:   odds ratio for cyclin A(ave) 2.7 [95% confidence interval (CI),   1.7-4.3] and cyclin A(max) 3.4 (CI, 2.1-5.5). Corresponding odds ratio   for Ki67 were Ki67(ave) 1.9 (CI, 1.2-3.1) and Ki67(max) 1.7 (CI,   1.1-2.7) and for grade 3.1 (CI, 1.8-5.1). Cyclin A was strongly   correlated to Ki67 and grade why a model including all was not   appropriate.   Conclusions: Cyclin A is a prognostic factor for breast cancer death in   node-negative patients using standardized methodology regarding scoring   and cutoff values. Adding cyclin A as a proliferative marker to established clinicopathologic factors will improve the separation of  low and high risk breast cancer.

  • 3.
    Blom, Johannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Yin, Li
    Lidén, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Dolk, Anders
    Jeppsson, Bengt
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nyrén, Olof
    A 9-year follow-up study of participants and nonparticipants in sigmoidoscopy screening: importance of self-selection2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 5, p. 1163-1168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Self-selection may compromise cost-effectiveness of screening programs. We hypothesized that nonparticipants have generally higher morbidity and mortality than participants. METHODS: A Swedish population-based random sample of 1,986 subjects ages 59 to 61 years was invited to sigmoidoscopy screening and followed up for 9 years by means of multiple record linkages to health and population registers. Gender-adjusted cancer incidence rate ratio (IRR) and overall and disease group-specific and mortality rate ratio (MRR) with 95% confidence intervals (95% CI) were estimated for nonparticipants relative to participants. Cancer and mortality rates were also estimated relative to the age-matched, gender-matched, and calendar period-matched Swedish population using standardized incidence ratios and standardized mortality ratios. RESULTS: Thirty-nine percent participated. The incidence of colorectal cancer (IRR, 2.2; 95% CI, 0.8-5.9), other gastrointestinal cancer (IRR, 2.7; 95% CI, 0.6-12.8), lung cancer (IRR, 2.2; 95% CI, 0.8-5.9), and smoking-related cancer overall (IRR, 1.4; 95% CI, 0.7-2.5) tended to be increased among nonparticipants relative to participants. Standardized incidence ratios for most of the studied cancers tended to be >1.0 among nonparticipants and <1.0 among participants. Mortality from all causes (MRR, 2.4; 95% CI, 1.7-3.4), neoplastic diseases (MRR, 1.9; 95% CI, 1.1-3.5), gastrointestinal cancer (MRR, 4.7; 95% CI, 1.1-20.7), and circulatory diseases (MRR, 2.3; 95% CI, 1.2-4.2) was significantly higher among nonparticipants than among participants. Standardized mortality ratio for the studied outcomes tended to be increased among nonparticipants and was generally decreased among participants. CONCLUSION: Individuals who might benefit most from screening are overrepresented among nonparticipants. This self-selection may attenuate the cost-effectiveness of screening programs on a population level.

  • 4. Bonn, Stephanie E
    et al.
    Sjölander, Arvid
    Lagerros, Ylva Trolle
    Wiklund, Fredrik
    Stattin, Pär
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Holmberg, Erik
    Grönberg, Henrik
    Bälter, Katarina
    Physical activity and survival among men diagnosed with prostate cancer2015In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 1, p. 57-64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Few studies have investigated the association between post-diagnosis physical activity and mortality among men diagnosed with prostate cancer. The aim of this study was to investigate the effect of physical activity after a prostate cancer diagnosis on both overall and prostate cancer-specific mortality in a large cohort.

    METHODS: Data from 4,623 men diagnosed with localized prostate cancer 1997-2002 and followed-up until 2012 were analyzed. HRs with 95% confidence intervals (CI) were estimated using Cox proportional hazards models to examine the association between post-diagnosis recreational MET-h/d, time spent walking/bicycling, performing household work or exercising, and time to overall and prostate cancer-specific death. All models were adjusted for potential confounders.

    RESULTS: During the follow-up, 561 deaths of any cause and 194 deaths from prostate cancer occurred. Statistically significantly lower overall mortality rates were found among men engaged in ≥5 recreational MET-h/d (HR, 0.63; 95% CI, 0.52-0.77), walking/bicycling ≥20 min/d (HR, 0.70; 95% CI, 0.57-0.86), performing household work ≥1 h/d (HR, 0.71; 95% CI, 0.59-0.86), or exercising ≥1 h/wk (HR, 0.74; 95% CI, 0.61-0.90), compared with less active men within each activity type. For prostate cancer-specific mortality, statistically significantly lower mortality rates were seen among men walking/bicycling ≥20 min/d (HR, 0.61; 95% CI, 0.43-0.87) or exercising ≥1 h/wk (HR, 0.68; 95% CI, 0.48-0.94).

    CONCLUSIONS: Higher levels of physical activity were associated with reduced rates of overall and prostate cancer-specific mortality.

    IMPACT: Our study further strengthens previous results indicating beneficial effects of physical activity on survival among men with prostate cancer.

  • 5. Campbell, Peter T
    et al.
    Newton, Christina C
    Kitahara, Cari M
    Patel, Alpa V
    Hartge, Patricia
    Koshiol, Jill
    McGlynn, Katherine A
    Adami, Hans-Olov
    Berrington de González, Amy
    Beane Freeman, Laura E
    Bernstein, Leslie
    Buring, Julie E
    Freedman, Neal D
    Gao, Yu-Tang
    Giles, Graham G
    Gunter, Marc J
    Jenab, Mazda
    Liao, Linda M
    Milne, Roger L
    Robien, Kim
    Sandler, Dale P
    Schairer, Catherine
    Sesso, Howard D
    Shu, Xiao-Ou
    Weiderpass, Elisabete
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Xiang, Yong-Bing
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Gapstur, Susan M
    Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies.2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 4, p. 597-606Article in journal (Refereed)
    Abstract [en]

    Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m2, HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m2, HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors.Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks.Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR.

  • 6. Chang, Ellen T.
    et al.
    Smedby, Karin Ekström
    Zhang, Shumin M.
    Hjalgrim, Henrik
    Melbye, Mads
    Öst, Åke
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Wolk, Alicja
    Adami, Hans-Olov
    Dietary factors and risk of non-hodgkin lymphoma in men and women2005In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 14, no 2, p. 512-20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased worldwide in recent decades. Diet could influence NHL risk by modulating the immune system, although evidence is limited. We did a population-based case-control study to determine whether differences in diet were associated with NHL risk. METHODS: A total of 597 NHL cases and 467 population controls in Sweden completed a semiquantitative food frequency questionnaire evaluating their dietary habits 2 years before the interview. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for associations between food intake and risk of NHL. RESULTS: High consumption of dairy products and fried red meat was associated with increased risk of NHL. The OR of NHL for individuals in the highest quartile compared with the lowest quartile of dairy intake was 1.5 (95% CI, 1.1-2.2; P(trend) = 0.003). The OR for the highest versus lowest quartile of fried red meat intake was 1.5 (95% CI, 1.0-2.1; P(trend) = 0.02). In contrast, high consumption of fruits and vegetables was associated with reduced risk of NHL, particularly follicular lymphoma, among women but not men. Compared with the lowest quartile of vegetable intake, the OR of follicular lymphoma among women in the highest quartile of vegetable intake was 0.3 (95% CI, 0.1-0.7; P(trend) = 0.002). CONCLUSIONS: The positive associations of NHL risk with dairy products and fried red meat and the inverse association with fruits and vegetables suggest that diet affects NHL risk and could explain the increase of some histopathogic subtypes.

  • 7.
    Chen, Lingjing
    et al.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Neovius, Martin
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Ekberg, Sara
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Martling, Anna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Eloranta, Sandra
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Work Loss Duration and Predictors Following Rectal Cancer Treatment among Patients with and without Prediagnostic Work Loss2016In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 25, no 6, p. 987-994Article in journal (Refereed)
    Abstract [en]

    Background: The number of working-age rectal cancer survivors is increasing due to early detection and improved treatment. However, work loss duration and predictors among them have not been studied thoroughly. Methods: We identified 3,438 patients with stage I-III rectal cancer, 18 to 61 years of age in the Swedish Colorectal Cancer Register 1996-2009. Information on work loss due to sick leave or disability pension was collected from 2 years before diagnosis to 5 years after (until December 31st, 2013). Incidence rate ratios (IRR) of work loss were estimated in a negative binominal model by clinical characteristics for the 1st and 2nd-5th years after diagnosis. Patients were stratified by prediagnostic work loss. Results: Patients without prediagnostic work loss (74%) experienced median 147 days (25th and 75th percentile: 55 and 281) of work loss during the 1st year after diagnosis. Work loss rates (2nd-5th years) were significantly increased among relapse-free patients diagnosed in stage III [IRR = 1.92; 95% confidence interval (CI), 1.52-2.43], operated with abdominoperineal resection (IRR = 1.26; 95% CI, 1.03-1.56), and treated with neoadjuvant (chemo) radiotherapy (IRR = 1.46; 95% CI, 1.06-2.02). Patients with prediagnostic work loss (26%) experienced median 336 days (25th and 75th percentile: 183 and 365) of work loss during the 1st year, and rates did not vary clinically till 5 years. Conclusion: Without prediagnostic work loss, disease-and treatment-related factors could help identify rectal cancer patients in need of early interventions to facilitate return to work. Impact: Clinical awareness around prediagnostic and postdiagnostic work loss and individualized cancer rehabilitation programs should be emphasized among cancer survivors.

  • 8. Cnattingius, Sven
    et al.
    Eloranta, Sandra
    Adami, Hans-Olov
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dickman, Paul W.
    Hsieh, Chung-cheng
    Mucci, Lorelei A.
    Trichopoulus, Dimitrius
    Lambe, Mats
    Johansson, Anna L. V.
    Placental weight and risk of invasive epithelial ovarian cancer with an early age of onset2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 9, p. 2344-2349Article in journal (Refereed)
    Abstract [en]

    Background: Epithelial ovarian cancer is associated with reproductive factors, but we lack knowledge if hormonal factors during pregnancy influence the mother's risk. Because pregnancy hormones are primarily produced by the placenta, placental weight may be an indirect marker of hormone exposure during pregnancy. Methods: In a nationwide Swedish cohort study, we included women with singleton births from 1982 to 1989. Women were followed for occurrence of invasive epithelial ovarian cancer, death, or emigration through 2004. Hazard ratios (HR) with 95% confidence intervals (95% CI) from Cox models were used to estimate associations between pregnancy exposures and epithelial ovarian cancer. Results: Among 395,171 women with information on placental weight in their first recorded birth, 316 women developed invasive epithelial ovarian cancer. Mean age at diagnosis was 44 years. Compared with women with a placental weight of 500 to 699 g, women with a high (>= 700 g) placental weight had an increased risk of developing epithelial ovarian cancer (HR, 1.47, 95% CI, 1.14-1.90). Compared with women with term pregnancies (40-41 weeks), women with post-term (>= 42 weeks) pregnancies had an increased risk of developing epithelial ovarian cancer (HR, 1.48, 95% CI, 1.00-2.19). These associations were slightly stronger when we included information about women's overall first birth, and slightly weaker when we included information about last recorded birth or ever last birth from 1982 to 1989. Conclusions: Because pregnancy hormone levels increase with placental weight, our study supports the hypothesis that hormone exposures during pregnancy influence the risk of invasive epithelial ovarian cancer among young women.

  • 9. Couch, Fergus J.
    et al.
    Gaudet, Mia M.
    Antoniou, Antonis C.
    Ramus, Susan J.
    Kuchenbaecker, Karoline B.
    Soucy, Penny
    Beesley, Jonathan
    Chen, Xiaoqing
    Wang, Xianshu
    Kirchhoff, Tomas
    McGuffog, Lesley
    Barrowdale, Daniel
    Lee, Andrew
    Healey, Sue
    Sinilnikova, Olga M.
    Andrulis, Irene L.
    Ozcelik, Hilmi
    Mulligan, Anna Marie
    Thomassen, Mads
    Gerdes, Anne-Marie
    Jensen, Uffe Birk
    Skytte, Anne-Bine
    Kruse, Torben A.
    Caligo, Maria A.
    von Wachenfeldt, Anna
    Barbany-Bustinza, Gisela
    Loman, Niklas
    Soller, Maria
    Ehrencrona, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Karlsson, Per
    Nathanson, Katherine L.
    Rebbeck, Timothy R.
    Domchek, Susan M.
    Jakubowska, Ania
    Lubinski, Jan
    Jaworska, Katarzyna
    Durda, Katarzyna
    Zlowocka, Elzbieta
    Huzarski, Tomasz
    Byrski, Tomasz
    Gronwald, Jacek
    Cybulski, Cezary
    Gorski, Bohdan
    Osorio, Ana
    Duran, Mercedes
    Isabel Tejada, Maria
    Benitez, Javier
    Hamann, Ute
    Hogervorst, Frans B. L.
    van Os, Theo A.
    van Leeuwen, Flora E.
    Meijers-Heijboer, Hanne E. J.
    Wijnen, Juul
    Blok, Marinus J.
    Kets, Marleen
    Hooning, Maartje J.
    Oldenburg, Rogier A.
    Ausems, Margreet G. E. M.
    Peock, Susan
    Frost, Debra
    Ellis, Steve D.
    Platte, Radka
    Fineberg, Elena
    Evans, D. Gareth
    Jacobs, Chris
    Eeles, Rosalind A.
    Adlard, Julian
    Davidson, Rosemarie
    Eccles, Diana M.
    Cole, Trevor
    Cook, Jackie
    Paterson, Joan
    Brewer, Carole
    Douglas, Fiona
    Hodgson, Shirley V.
    Morrison, Patrick J.
    Walker, Lisa
    Porteous, Mary E.
    Kennedy, M. John
    Side, Lucy E.
    Bove, Betsy
    Godwin, Andrew K.
    Stoppa-Lyonnet, Dominique
    Fassy-Colcombet, Marion
    Castera, Laurent
    Cornelis, Francois
    Mazoyer, Sylvie
    Leone, Melanie
    Boutry-Kryza, Nadia
    Bressac-de Paillerets, Brigitte
    Caron, Olivier
    Pujol, Pascal
    Coupier, Isabelle
    Delnatte, Capucine
    Akloul, Linda
    Lynch, Henry T.
    Snyder, Carrie L.
    Buys, Saundra S.
    Daly, Mary B.
    Terry, MaryBeth
    Chung, Wendy K.
    John, Esther M.
    Miron, Alexander
    Southey, Melissa C.
    Hopper, John L.
    Goldgar, David E.
    Singer, Christian F.
    Rappaport, Christine
    Tea, Muy-Kheng M.
    Fink-Retter, Anneliese
    Hansen, Thomas V. O.
    Nielsen, Finn C.
    Arason, Adalgeir
    Vijai, Joseph
    Shah, Sohela
    Sarrel, Kara
    Robson, Mark E.
    Piedmonte, Marion
    Phillips, Kelly
    Basil, Jack
    Rubinstein, Wendy S.
    Boggess, John
    Wakeley, Katie
    Ewart-Toland, Amanda
    Montagna, Marco
    Agata, Simona
    Imyanitov, Evgeny N.
    Isaacs, Claudine
    Janavicius, Ramunas
    Lazaro, Conxi
    Blanco, Ignacio
    Feliubadalo, Lidia
    Brunet, Joan
    Gayther, Simon A.
    Pharoah, Paul P. D.
    Odunsi, Kunle O.
    Karlan, Beth Y.
    Walsh, Christine S.
    Olah, Edith
    Teo, Soo Hwang
    Ganz, Patricia A.
    Beattie, Mary S.
    van Rensburg, Elizabeth J.
    Dorfling, Cecelia M.
    Diez, Orland
    Kwong, Ava
    Schmutzler, Rita K.
    Wappenschmidt, Barbara
    Engel, Christoph
    Meindl, Alfons
    Ditsch, Nina
    Arnold, Norbert
    Heidemann, Simone
    Niederacher, Dieter
    Preisler-Adams, Sabine
    Gadzicki, Dorothea
    Varon-Mateeva, Raymonda
    Deissler, Helmut
    Gehrig, Andrea
    Sutter, Christian
    Kast, Karin
    Fiebig, Britta
    Heinritz, Wolfram
    Caldes, Trinidad
    de la Hoya, Miguel
    Muranen, Taru A.
    Nevanlinna, Heli
    Tischkowitz, Marcd.
    Spurdle, Amanda B.
    Neuhausen, Susan L.
    Ding, Yuan Chun
    Lindor, Noralane M.
    Fredericksen, Zachary
    Pankratz, V. Shane
    Peterlongo, Paolo
    Manoukian, Siranoush
    Peissel, Bernard
    Zaffaroni, Daniela
    Barile, Monica
    Bernard, Loris
    Viel, Alessandra
    Giannini, Giuseppe
    Varesco, Liliana
    Radice, Paolo
    Greene, Mark H.
    Mai, Phuong L.
    Easton, Douglas F.
    Chenevix-Trench, Georgia
    Offit, Kenneth
    Simard, Jacques
    Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 4, p. 645-657Article in journal (Refereed)
    Abstract [en]

    Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

    Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined.

    Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)).

    Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers.

    Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers.

  • 10. Delahaye-Sourdeix, Manon
    et al.
    Urayama, Kevin Y
    Gaborieau, Valérie
    Veenstra, Rianne
    Foll, Matthieu
    Chabrier, Amelie
    Benavente, Yolanda
    Nieters, Alexandra
    Becker, Nikolaus
    Foretova, Lenka
    Maynadié, Marc
    Staines, Anthony
    Smedby, Karin Ekstrom
    Glimelius, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lightfoot, Tracy
    Cocco, Pierluigi
    Galan, Pilar
    Vatten, Lars J
    Duell, Eric J
    Kiemeney, Lambertus
    Roman, Eve
    de Sanjosé, Silvia
    Lathrop, Mark
    Melbye, Mads
    Brennan, Paul
    Diepstra, Arjan
    van den Berg, Anke
    Hjalgrim, Henrik
    Jarrett, Ruth F
    McKay, James D
    A Novel Risk Locus at 6p21.3 for Epstein-Barr Virus-Positive Hodgkin Lymphoma2015In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 12, p. 1838-1843Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region.

    METHODS: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.

    RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 × 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 0.92-1.21), indicating that this association was specific to the EBV-positive subgroup (Phet < P = 10(-8)). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histologic subtype of cHL.

    CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL.

    IMPACT: This expands the number of genetic variants that are associated with cHL and provides additional evidence for a critical and specific role of EBV in the etiology of this disease. Cancer Epidemiol Biomarkers Prev; 24(12); 1838-43.

  • 11.
    Eaker, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Dickman, Paul W.
    Hellström, Vivan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Zack, Matthew M.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Regional differences in breast cancer survival despite common guidelines2005In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 14, no 12, p. 2914-8Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Despite a uniform regional breast cancer care program, breast cancer survival differs within regions. We therefore examined breast cancer survival in relation to differences in diagnostic activity, tumor characteristics, and treatment in seven Swedish counties within a single health care region. METHODS: We conducted a population-based observational study using a clinical breast cancer register in one Swedish health care region. Eligible women (n = 7,656) ages 40 to 69 years diagnosed with primary breast cancer between 1992 and 2002 were followed up until 2003. The 7-year relative survival ratio was used to estimate breast cancer survival. Excess mortality was modeled using Poisson regression to study differences in survival between counties. RESULTS: The 7-year relative survival for breast cancer patients was significantly lower (up to 7% in absolute risk difference) in one county (county A) compared with the others. This difference existed only among women diagnosed before 1998, ages 50 to 59 years, and was strongest among stage II breast cancer patients. Adjustment for amount of diagnostic activity eliminated the survival differences among the counties. The amount of diagnostic activity was also lower in county A during the same time period. After county A, during 1997-1998, began to adhere strictly to the regional breast cancer care program, neither any survival differences nor diagnostic activity differences were observed. INTERPRETATIONS: Markers of diagnostic activity explained survival differences within our region, and the underlying mechanisms may be several. Low diagnostic activity may entail later diagnosis or inadequate characterization of the tumor and thereby missed treatment opportunities. Strengthening of multidisciplinary management of breast cancer can improve survival.

  • 12. Engel, Christoph
    et al.
    Versmold, Beatrix
    Wappenschmidt, Barbara
    Simard, Jacques
    Easton, Douglas F.
    Peock, Susan
    Cook, Margaret
    Oliver, Clare
    Frost, Debra
    Mayes, Rebecca
    Evans, D. Gareth
    Eeles, Rosalind
    Paterson, Joan
    Brewer, Carole
    McGuffog, Lesley
    Antoniou, Antonis C.
    Stoppa-Lyonnet, Dominique
    Sinilnikova, Olga M.
    Barjhoux, Laure
    Frenay, Marc
    Michel, Cecile
    Leroux, Dominique
    Dreyfus, Helene
    Toulas, Christine
    Gladieff, Laurence
    Uhrhammer, Nancy
    Bignon, Yves-Jean
    Meindl, Alfons
    Arnold, Norbert
    Varon-Mateeva, Raymonda
    Niederacher, Dieter
    Preisler-Adams, Sabine
    Kast, Karin
    Deissler, Helmut
    Sutter, Christian
    Gadzicki, Dorothea
    Chenevix-Trench, Georgia
    Spurdle, Amanda B.
    Chen, Xiaoqing
    Beesley, Jonathan
    Olsson, Hakan
    Kristoffersson, Ulf
    Ehrencrona, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Liljegren, Annelie
    van der Luijt, Rob B.
    van Os, Theo A.
    van Leeuwen, Flora E.
    Domchek, Susan M.
    Rebbeck, Timothy R.
    Nathanson, Katherine L.
    Osorio, Ana
    Ramon y Cajal, Teresa
    Konstantopoulou, Irene
    Benitez, Javier
    Friedman, Eitan
    Kaufman, Bella
    Laitman, Yael
    Mai, Phuong L.
    Greene, Mark H.
    Nevanlinna, Heli
    Aittomaki, Kristiina
    Szabo, Csilla I.
    Caldes, Trinidad
    Couch, Fergus J.
    Andrulis, Irene L.
    Godwin, Andrew K.
    Hamann, Ute
    Schmutzler, Rita K.
    Association of the Variants CASP8 D302H and CASP10 V410I with Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 11, p. 2859-2868Article in journal (Refereed)
    Abstract [en]

    Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population. Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; P-trend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; P-trend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers. Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers. Impact: The combined application of these and other recently identified genetic risk modifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.

  • 13. Fall, Katja
    et al.
    Garmo, Hans
    Gudbjornsdottir, Soffia
    Stattin, Par
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Diabetes Mellitus and Prostate Cancer Risk; A Nationwide Case-Control Study within PCBaSe Sweden2013In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 22, no 6, p. 1102-1109Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes mellitus (DM) increases the risk for cancer at almost all sites, but data on the association with prostate cancer are inconsistent. Methods: We assessed the risk of a prostate cancer diagnosis among men with type 2 (T2)DM in a nationwide population-based case-control study including 44,352 men with prostate cancer identified through the Prostate Cancer data Base Sweden (PCBaSe) between 2002 and 2006 and 221,495 age-matched men from the general population. Results: Overall, the risk of prostate cancer among men with T2DM was lower than among men without T2DM [OR, 0.80; 95% confidence interval (CI), 0.76-0.85]. The risk decreased with longer disease duration and was observed across all tumor risk categories, although most clearly among men with low risk tumors (OR, 0.71; 95% CI, 0.64-0.80). The risk for prostate cancer was reduced among diabetic men on dietary treatment only (OR, 0.89; 95% CI, 0.80-0.99) but more markedly among men on oral hypoglycemic agents (OR, 0.80; 95% CI, 0.74-0.87) and insulin (OR, 0.72; 95% CI, 0.69-0.81). Obese diabetic men (BMI > 30 kg/m(2)) showed a reduced risk (OR, 0.72; 95% CI, 0.65-0.80) compared with men without diabetes. There was a trend of decreasing risk with increasing levels of HbA1c (P < 0.05). Conclusions: This nationwide study confirmed a reduced risk of being diagnosed with prostate cancer among men with T2DM, especially for low-risk tumors. An altered hormonal milieu is a plausible explanation, although the possibility of decreased prostate cancer detection among diabetic men cannot be ruled out. Impact: This is the largest study to examine the association between T2DM and prostate cancer accounting for tumor risk group and diabetes treatment.

  • 14. Fletcher, Olivia
    et al.
    Johnson, Nichola
    Dos Santos Silva, Isabel
    Kilpivaara, Outi
    Aittomäki, Kristiina
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Nevanlinna, Heli
    Wasielewski, Marijke
    Meijers-Heijerboer, Hanne
    Broeks, Annegien
    Schmidt, Marjanka K.
    Van't Veer, Laura J.
    Bremer, Michael
    Dörk, Thilo
    Chekmariova, Elena V.
    Sokolenko, Anna P.
    Imyanitov, Evgeny N.
    Hamann, Ute
    Rashid, Muhammad U.
    Brauch, Hiltrud
    Justenhoven, Christina
    Ashworth, Alan
    Peto, Julian
    Family history, genetic testing, and clinical risk prediction: pooled analysis of CHEK2 1100delC in 1,828 bilateral breast cancers and 7,030 controls2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 1, p. 230-4Article in journal (Refereed)
    Abstract [en]

    If breast cancers arise independently in each breast the odds ratio (OR) for bilateral breast cancer for carriers of CHEK2 1100delC should be approximately 5.5, the square of the reported OR for a first primary (OR, 2.34). In the subset of bilateral cases with one or more affected relatives, the predicted carrier OR should be approximately 9. We have tested these predictions in a pooled set of 1,828 cases with 2 primaries and 7,030 controls from 8 studies. The second primary OR for CHEK2 1100delC carriers was 6.43 (95% confidence interval, 4.33-9.56; P < 0.0001), significantly greater than the published estimate for a first primary (P < 0.001) but consistent with its square. The predicted increase in carrier OR with increasing numbers of affected relatives was seen using bilateral cases from the UK (P(trend) = 0.0003) and Finland (P(trend) = 0.37), although not using those from the Netherlands and Russia (P = 0.001 for heterogeneity between countries). Based on a standard genetic model, we predict lifetime risks for CHEK2 1100delC carrier and noncarrier daughters of bilateral breast cancer cases of 37% and 18%, respectively. Our results imply that clinical management of the daughter of a woman with bilateral breast cancer should depend on her CHEK2 1100delC carrier status. This and other moderate penetrance breast cancer susceptibility alleles, together with family history data, will thus identify increasing numbers of women at potentially very high risk. Before such predictions are accepted by clinical geneticists, however, further population-based evidence is needed on the effect of CHEK2 1100delC and other moderate penetrance alleles in women with a family history of breast cancer.

  • 15. Genkinger, Jeanine M.
    et al.
    Li, Ruifeng
    Spiegelman, Donna
    Anderson, Kristin E.
    Albanes, Demetrius
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Bernstein, Leslie
    Black, Amanda
    van den Brandt, Piet A.
    English, Dallas R.
    Freudenheim, Jo L.
    Fuchs, Charles S.
    Giles, Graham G.
    Giovannucci, Edward
    Goldbohm, R. Alexandra
    Horn-Ross, Pamela L.
    Jacobs, Eric J.
    Koushik, Anita
    Mannisto, Satu
    Marshall, James R.
    Miller, Anthony B.
    Patel, Alpa V.
    Robien, Kim
    Rohan, Thomas E.
    Schairer, Catherine
    Stolzenberg-Solomon, Rachael
    Wolk, Alicja
    Ziegler, Regina G.
    Smith-Warner, Stephanie A.
    Coffee, Tea, and Sugar-Sweetened Carbonated Soft Drink Intake and Pancreatic Cancer Risk: A Pooled Analysis of 14 Cohort Studies2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 2, p. 305-318Article in journal (Refereed)
    Abstract [en]

    Background: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. Methods: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. Results: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing >= 900 to <0 g/d; 237g approximate to 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing >= 400 to 0 g/d; 237g approximate to 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing >= 250 to 0 g/d; 355g approximate to 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). Conclusion and Impact: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

  • 16. Genkinger, Jeanine M.
    et al.
    Spiegelman, Donna
    Anderson, Kristin E.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Bernstein, Leslie
    van den Brandt, Piet A.
    English, Dallas R.
    Freudenheim, Jo L.
    Fuchs, Charles S.
    Giles, Graham G.
    Giovannucci, Edward
    Hankinson, Susan E.
    Horn-Ross, Pamela L.
    Leitzmann, Michael
    Mannisto, Satu
    Marshall, James R.
    McCullough, Marjorie L.
    Miller, Anthony B.
    Reding, Douglas J.
    Robien, Kim
    Rohan, Thomas E.
    Schatzkin, Arthur
    Stevens, Victoria L.
    Stolzenberg-Solomon, Rachael Z.
    Verhage, Bas A. J.
    Wolk, Alicja
    Ziegler, Regina G.
    Smith-Warner, Stephanie A.
    Alcohol Intake and Pancreatic Cancer Risk: A Pooled Analysis of Fourteen Cohort Studies2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 3, p. 765-776Article, review/survey (Refereed)
    Abstract [en]

    Background: Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk. Methods: We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks and 95% confidence intervals were calculated using Cox proportional hazards models and then pooled using a random effects model. Results: A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate relative risk, 1.22; 95% confidence interval, 1.03-1.45 comparing >= 30 to 0 grams/day of alcohol; P value, test for between-studies heterogeneity = 0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (P value, test for interaction = 0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of >= 5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared with overweight and obese individuals (P value, test for interaction = 0.01). Discussion: Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day. (Cancer Epidemiol Biomarkers Prev 2009;18(3):765-76)

  • 17.
    Ghanipour, Arezo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Jirström, Karin
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    The prognostic significance of tryptophanyl-tRNA synthetase in colorectal cancer2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 11, p. 2949-2956Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tryptophanyl-tRNA synthetase (TrpRS) is an aminoacyl-tRNA synthetase involved in protein synthesis and regulation of RNA transcription and translation and is an inhibitor of angiogenesis. TrpRS has been shown to be differentially expressed in colorectal cancer (CRC) and has thus been identified as a potential prognostic marker. The aim of this study was to analyze the correlation of TrpRS to the prognosis of patients diagnosed and treated for CRC within a defined population. METHODS: With a polyclonal, monospecific IgG antibody, TrpRS expression was assessed by immunohistochemistry on tissue microarrays with tumors from a population-based CRC cohort (n = 320). Staining intensity and fraction of positive tumor cells were recorded. A Cox multivariate model including TrpRS expression, carcinoembryonic antigen, age, stage, tumor differentiation, and lymphatic and vascular vessel invasion was used to calculate the hazard ratio and 95% confidence interval (95% CI) for time to recurrence, disease-free survival, and overall survival. RESULTS: Low expression of TrpRS correlated to increased risk for lymph node metastasis (P = 0.025) and a more advanced tumor stage (P = 0.001). Patients with tumors and increased levels of TrpRS expression had better survival than patients with low expression levels. Multivariate analyses revealed significantly better disease-free survival (relative risk, 0.59; 95% CI, 0.38-0.95) for patients with high expression than for patients with low expression of TrpRS. For colon cancer patients, a reduced risk for recurrence was seen in patients with increased TrpRS expression (relative risk, 0.23; 95% CI, 0.07-0.80). CONCLUSION: Low expression of TrpRS in tumor tissue correlates with increased risk for recurrence and worse survival in patients with CRC. This can be related to its antiangiogenic properties and could aid in the future selection of new drugs in the treatment of CRC.

  • 18.
    Grundmark, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Loda, Massimo
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 8, p. 2088-2096Article in journal (Refereed)
    Abstract [en]

    Background:

    Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration.

    Methods:

    In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS.

    Results:

    Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF].

    Conclusions:

    The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer.

  • 19. Hjalgrim, Henrik
    et al.
    Ekström-Smedby, Karin
    Rostgaard, Klaus
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hamilton-Dutoit, Stephen
    Schöllkopf, Claudia
    Chang, Ellen T.
    Ralfkiaer, Elisabeth
    Adami, Hans-Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Melbye, Mads
    Cigarette smoking and risk of Hodgkin lymphoma: a population-based case-control study2007In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 16, no 8, p. 1561-1566Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies have inconsistently reported an association between tobacco smoking and Hodgkin lymphoma (HL) risk. The conflicting finding may reflect etiologic heterogeneity between HL subtypes, warranting further characterization of the relationship. METHODS: We collected information on tobacco-smoking habits in 586 classic HL cases and 3,187 population controls in a Danish-Swedish case-control study. HL EBV status was established for 499 cases by standard techniques. Odds ratios (OR) for an association with cigarette smoking were calculated by logistic regression for HL overall and stratified by age, sex, major histology subtypes, and tumor EBV status, adjusting for known confounders. RESULTS: Compared with never smokers, current cigarette smokers were at an increased overall HL risk [adjusted OR, 1.57; 95% confidence interval (95% CI), 1.22-2.03]. The association was strongest for EBV-positive HL (adjusted OR, 2.36; 95% CI, 1.51-3.71), but also applied to EBV-negative HL (adjusted OR, 1.43; 95% CI, 1.05-1.97; P(homogeneity EBV-pos) versus P(homogeneity EBV-neg) = 0.04). The association did not vary appreciably by age, sex, or histologic subtype, the apparent EBV-related difference present in all strata. There was no evidence of a dose-response pattern, whether by age at smoking initiation, daily cigarette consumption, number of years smoking, or cumulative number of cigarettes smoked. Similar results were obtained in analyses using non-HL patients (n = 3,055) participating in the founding study as comparison group. CONCLUSION: The observed association between cigarette smoking and HL risk is consistent with previous findings and biologically credible. Although not easily dismissed as an artifact, the limited evidence of a dose-response pattern renders the overall evidence of causality weak.

  • 20.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In an earlier publication, our evaluation of data from breast cancer screening programs in seven Swedish counties suggested a 40% reduction in incidence-based breast cancer mortality among women actually screened. In the current study, we expand the previous analysis from seven counties to 13 large areas within nine counties, including six of the original counties and seven additional areas, examine a longer period of follow-up (20-44 years), apply new analytic methods for the evaluation of incidence-based breast cancer mortality, and estimate the number needed to screen to save one life.METHODS: Data from six of the original counties (one being excluded as it does not yet have 10 years of follow-up after the initiation of screening), with increased follow-up, and seven additional large areas, within three counties, representing approximately 45% of Swedish women, provide information about age at diagnosis, age at death, and screening history for 542,187 women in the prescreening and 566,423 women in the screening epochs. Regardless of year of diagnosis, there were a total of 6,231 deaths due to breast cancer in the period of study as a whole. Of these, 4,778 were incidence-based deaths in the two epochs, i.e., death among cases diagnosed within either the prescreening or screening period. Data were analyzed using Poisson regression and adjusted, when necessary, for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.RESULTS: Attendance was uniformly high, averaging 75% in the screening epochs. Recall rates for assessment varied from 4% to 5% at the first round of screening and approximately 3% at later rounds. Detection rates averaged five breast cancers per 1,000 women screened in the first round, and four breast cancers per 1,000 women screened in subsequent rounds. There was a significant 45% reduction in incidence-based breast cancer mortality among screened women in the screening epoch relative to incidence-based breast cancer mortality in the prescreening epoch (relative risk, 0.55; 95% confidence intervals, 0.51-0.59). After adjusting for self-selection bias, there still was a significant 43% reduction in incidence-based breast cancer mortality associated with screening (relative risk, 0.57; 95% confidence intervals, 0.53-0.62).CONCLUSIONS: These results indicate a reduction in breast cancer mortality of between 40% and 45% in association with screening, after adjustment for self-selection bias. These results were obtained with modest human costs: the number needed to screen to save one life was estimated as 472.

  • 21.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Reduction in breast cancer mortality from the organised service screening with mammography: 2. Validation with alternative analytic methods2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 1, p. 52-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In our companion article, incidence-based mortality analysis of data from breast cancer screening programs in 13 areas in Sweden indicated a 40% to 45% reduction in incidence-based breast cancer mortality among women actually screened. In this article, we apply new analytic methods for the evaluation of breast cancer mortality, using all breast cancer deaths in the period under study.METHODS: Data were available from 13 areas on breast cancer mortality by year of diagnosis, year of death, and screening exposure. The period of study varied by area, the overall range of year of diagnosis being 1968 to 2001. We had data on 6,231 deaths and an average population of 555,676 women ages 40 to 69 years. Analysis of the effect of being screened was conducted using an alternative statistical analysis applied to all breast cancer deaths in the period of study, in addition to the incidence-based mortality analysis in our companion article. Data were analyzed using Poisson regression and adjusted for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.RESULTS: Using all deaths in the period of observation, a significant 42% reduction in breast cancer mortality was observed, adjusting for contemporaneous changes independent of screening [relative risk (RR), 0.58; 95% confidence interval (95% CI), 0.53-0.62]. After further adjustment for self-selection bias, the mortality reduction was 39% (RR, 0.61; 95% CI, 0.55-0.68), also highly significant.CONCLUSIONS: These results indicate a reduction in breast cancer mortality of 39% in association with screening, after adjustment for contemporaneous changes and self-selection bias. These results confirm previous conclusions arrived at using incidence-based mortality analyses.

  • 22.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Baron, John A.
    Byers, Tim
    Wolk, Alicja
    Ohlander, Eva-May
    Zack, Matthew
    Adami, Hans-Olov
    Alcohol intake and breast cancer risk: effect of exposure from 15 years of age1995In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 4, no 8, p. 843-847Article in journal (Refereed)
    Abstract [en]

    Research regarding the relationship between alcohol intake and breast cancer risk has suggested an association between the two, although the data are inconsistent regarding dose effects and susceptible populations. To clarify these issues, we investigated the association of breast cancer risk with alcohol intake at various ages in a population-based case-control study nested within a screening cohort in Sweden. Subjects were women 40-75 years old who participated in a screening program in central Sweden. Information about personal characteristics, diet, and alcohol intake was obtained by a questionnaire sent out at the invitation to the screening interview and at a supplementary interview conducted among a sample of women who did and did not develop breast cancer. Alcohol intake did not affect breast cancer risk among women under 50 years old. However, among those over 50 years of age, ever-drinking conferred a relative risk of 1.8 (95% confidence interval = 1.2-2.6). Current and former drinkers had similar increases in risk. No particular latent period of alcohol effect was identified, but drinking later in life to have a bigger effect than did drinking earlier in life.

  • 23. Kulmala, Satu-Maria A.
    et al.
    Shabalova, Irena P.
    Petrovitchev, Nikolay
    Syrjänen, Kari J.
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Johansson, Bo C.
    Syrjänen, Stina M.
    Tosi, P.
    Type-specific persistence of high-risk human papillomavirus infections in the New Independent States of the former Soviet Union Cohort Study2007In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 16, no 1, p. 17-22Article in journal (Refereed)
    Abstract [en]

    Background: Prospective follow-up studies have recently suggested that persistent high-risk human papillomavirus (HPV) infections play a key role in the progression of CIN lesions and in the development of cervical cancer. However, data on type-specific persistence, viral integration, and the role of multiple infections are scanty.

    Materials and Methods: A cross-sectional/cohort study was conducted between 1998 and 2002 in three New Independent States of the former Soviet Union comprising a cohort of 3,187 women, of whom 854 women were followed up for a mean of 17 months (SD, 11.6). HPV genotyping was done with real-time PCR, detecting HPV types 16, 18/45, 31, 33/52/58, 35, and 39. The integration status of HPV16 was examined by using a novel Taqman-based PCR method.

    Results: The mean clearance time for the individual high– risk–type infection was 16.5 months (range = 0.9-34.9 months). HPV16 and HPV31 were the most persistent infections (clearance times = 18.1 and 16.2 months, respectively), whereas HPV39 infections cleared most rapidly. The mean copies per cell in HPV18/45, HPV31, HPV33/52/58, and HPV39 infections were higher in persisting HPV infections than in HPV infections that cleared, but the difference was not significant. Integration of HPV16 was not found to correlate with HPV persistence.

    Conclusions: A large proportion of women remained high-risk HPV positive after 18 months. Coinfection with multiple HPV types, viral load, or integration status did not correlate with persistence of high-risk HPV infections.

  • 24. Lambe, Mats
    et al.
    Hsieh, Chung-Cheng
    Tsaih, Shirng-wern
    Adami, Johanna
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Adami, Hans-Olov
    Childbearing and the risk of Hodgkin's disease1998In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 7, no 9, p. 831-834Article in journal (Refereed)
    Abstract [en]

    The causes of Hodgkin's disease remain incompletely known, but a higher incidence in men than in women has prompted an interest in the role of female sex hormones and reproductive history. Available epidemiological data are, however, contradictory. We analyzed possible associations between parity, age at first birth, and the risk of developing Hodgkin's disease by a linkage between the Swedish Cancer Register and a nationwide Fertility Register. Among women born between 1925 and 1972, 917 cases with Hodgkin's disease and concomitant fertility information were identified. For each case patient, five age-matched controls were randomly selected among women in the Fertility Register. Conditional logistic regression was used to estimate odds ratios of Hodgkin's disease associated with a birth. We found a slightly and nonsignificantly reduced risk of Hodgkin's disease in ever-parous compared with nulliparous women. Among parous women, the number of children was unrelated to risk, whereas there was some evidence of an increased risk with late age at first birth in women under age 45 at diagnosis. No clear temporal relations between childbearing and subsequent risk were discernible in any parity or age group. Although uncontrolled confounding might have affected our results, they do not indicate that hormonal or immunological changes associated with childbearing play a role in the development of Hodgkin's disease.

  • 25.
    Larfors, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Parental Age, Family Size, and Offspring's Risk of Childhood and Adult Acute Leukemia2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 7, p. 1185-1190Article in journal (Refereed)
    Abstract [en]

    Background: An association between childhood acute leukemia and advanced parental age was observed more than 50 years ago, and the association has been repeated in several, but not all, subsequent studies. In contrast to the many studies addressing childhood leukemia, few have included adult patients.

    Methods: In this register-based case control study, we examined the association between parental age and incidence of acute leukemia in 2,660 childhood cases and 4,412 adult cases of acute leukemia, compared with 28,288 age-matched controls selected from a population-based register. Relative risks were estimated with conditional logistic regression.

    Results: We found a small increased risk of childhood acute lymphoblastic leukemia with increasing paternal age (adjusted OR, 1.05 per 5-year increase in age). Risk estimates were similar for childhood acute myeloid leukemia (AML), whereas no association was found with adult leukemia. Meanwhile, we observed a decreased risk of adult AML with increasing number of siblings, both older and younger.

    Conclusions: The results support the idea of a prenatal etiology of leukemia but indicate that parental age effects are limited to childhood cases. Impact: This is the first large study on parental age and leukemia risk, which includes adult cases. The finding on family size and risk of adult AM L needs to be validated in future studies.

  • 26.
    Larfors, Gunnar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lambert, Paul C.
    Lambe, Mats
    Ekbom, Anders
    Cnattingiusi, Sven
    Placental Weight and Breast Cancer Survival in Young Women2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 3, p. 777-783Article in journal (Refereed)
    Abstract [en]

    A growing body of evidence indicates that reproductive history influences survival in breast cancer, especially among women diagnosed during or shortly after a pregnancy. However, little is known about the underlying mechanisms. We hypothesized that increasing placental weight, as an indirect marker of exposure to elevated hormone levels during pregnancy, would be associated with reduced survival in breast cancer. A cohort of 1873 women with at least one pregnancy after January 1st, 1973, and a subsequent breast cancer diagnosis before the end of 1991 were followed up for death or emigration through 2006. Information on placental weight and potential confounding factors were collected from medical records and from nationwide registers, which resulted in data on placental weight in the most recent pregnancy before diagnosis for 1,057 cases. For each 100-gram increase in placental weight, the adjusted hazard ratio of death was 1.09 [95% confidence interval (CI), 0.99-1.19]. The association was stronger among primiparous women (adjusted hazard ratio, 1.26; 95% CI, 1.09-1.47), and among women diagnosed during pregnancy or within 2 years from last birth (adjusted hazard ratio, 1.30; 95% CI, 1.06-1.59). Increasing placental weight is associated with reduced breast cancer survival. These findings are consistent with the hypothesis that the reduced survival in breast cancer among women with a recent childbirth is linked to pregnancy hormone exposure.

  • 27. Larsson, Susanna C.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, Alicja
    Folate Intake and Risk of Breast Cancer by Estrogen and Progesterone Receptor Status in a Swedish Cohort2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 12, p. 3444-3449Article in journal (Refereed)
    Abstract [en]

    Background: Folate is a B vitamin involved in one-carbon metabolism and has been postulated to influence the risk of breast cancer. However, epidemiologic studies of folate intake in relation to breast cancer risk are inconclusive. We examined the association between dietary folate intake and the risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumor in the Swedish Mammography Cohort. Methods: Our study population consisted of 61,433 women who completed a food frequency questionnaire at baseline (1987-1990) and again in 1997. Cox proportional hazards models were used to estimate rate ratios (RR) with 95% confidence intervals (95% CI). Results: During an average of 17.4 years of follow-up, 2,952 incident cases of invasive breast cancer were ascertained. We observed no association between dietary folate intake and risk of total breast cancer or ER+/PR+ or ER-/PR- tumors. The multivariate RR of total breast cancer comparing extreme quintiles of folate intake was 1.01 (95%a CI, 0.90-1.13; P-trend = 0.84). However, folate intake was inversely associated with risk of ER+/PR- breast cancer (n = 417 cases; RR for highest versus lowest quintile, 0.79; 95% CI, 0.59-1.07; Ptrend = 0.01). Results did not vary by alcohol intake or menopausal status. Conclusions: These findings do not support an overall association between folate intake and risk of breast cancer but suggest that folate intake may be inversely associated with ER+/PR- tumors.

  • 28. Larsson, Susanna C.
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wolk, Alicja
    Fruit and vegetable consumption and incidence of gastric cancer: a prospective study2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 10, p. 1998-2001Article in journal (Refereed)
    Abstract [en]

    Background: Whether fruit and vegetable consumption may confer protection from gastric cancer remains controversial.

    Methods: We prospectively investigated the association between consumption of fruits and vegetables and the incidence of gastric cancer among participants from two population-based cohort studies: 36,664 women in the Swedish Mammography Cohort and 45,338 men in the Cohort of Swedish Men. Participants completed a food-frequency questionnaire in 1997 and were followed up for cancer incidence through June 2005. Cox proportional hazards models were used to estimate multivariate hazard ratios (HR) and 95% confidence intervals (95% CI).

    Results: During a mean follow-up of 7.2 years, we ascertained 139 incident cases of gastric cancer. Vegetable consumption was inversely associated with risk of gastric cancer, whereas no significant association was observed for fruit consumption. After controlling for age and other risk factors, women and men who consumed >= 2.5 servings/d of vegetables had a HR of 0.56 (95% CI, 0.34-0.93) for developing gastric cancer compared with those who consumed < 1 serving/d. The respective HR for fruit consumption was 0.86 (95% CI, 0.52-1.43). Among specific subgroups of vegetables, consumption of green leafy vegetables and root vegetables was inversely associated with risk of gastric cancer, the multivariate HRs comparing >= 3 servings/wk with < 0.5 serving/wk were 0.64 (95% CI, 0.42-0.99) for green leafy vegetables and 0.43 (95% CI, 0.27-0.69) for root vegetables.

    Conclusions: Frequent consumption of vegetables may reduce the risk of gastric cancer.

  • 29. Lee, Eunjung
    et al.
    Stram, Daniel O
    Ek, Weronica E
    Onstad, Lynn E
    MacGregor, Stuart
    Gharahkhani, Puya
    Ye, Weimin
    Lagergren, Jesper
    Shaheen, Nicholas J
    Murray, Liam J
    Hardie, Laura J
    Gammon, Marilie D
    Chow, Wong-Ho
    Risch, Harvey A
    Corley, Douglas A
    Levine, David M
    Whiteman, David C
    Bernstein, Leslie
    Bird, Nigel C
    Vaughan, Thomas L
    Wu, Anna H
    Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk.2015In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.

    METHODS: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.

    RESULTS: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.

    CONCLUSIONS: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus.

    IMPACT: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus. Cancer Epidemiol Biomarkers Prev; 24(11); 1801-3. ©2015 AACR.

  • 30. Melvin, Jennifer C.
    et al.
    Seth, Divya
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Hammar, Niklas
    Jungner, Ingmar
    Walldius, Goran
    Lambe, Mats
    Wigertz, Annette
    Van Hemelrijck, Mieke
    Lipid Profiles and Risk of Breast and Ovarian Cancer in the Swedish AMORIS Study2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 8, p. 1381-1384Article in journal (Refereed)
    Abstract [en]

    Background: Obesity is a risk factor for breast and ovarian cancer; the mechanisms of action are not completely understood. Perturbed lipid metabolism often accompanies obesity; we therefore ascertained the associations between lipid components and breast and ovarian cancer risk in a prospective cohort study.

    Methods: A total of 234,494 women with baseline measurements of triglycerides and total cholesterol and glucose were selected from the AMORIS database.A total of 27,394 had measurements of high-density lipoprotein, low-density lipoprotein, apolipoprotein (Apo) B, and A-I. Associations between quartiles and dichotomized values of lipid components and breast and ovarian cancer risk were analyzed using Cox proportional hazard models.

    Results: We identified 6,105 women diagnosed with breast cancer and 808 women diagnosed with ovarian cancer. A weak trend was observed between triglycerides and breast cancer (HR, 1.01, 95% Confidence Interval, 0.94-1.09; 0.93 (0.86-1.00) 0.91 (0.84-0.99), second, third, and fourth quartiles; P = 0.01). No other associations between lipid components and risk of breast cancer or ovarian cancer showed statistical significance.

    Conclusions: A weak protective association was found between levels of triglycerides and risk of breast cancer.

    Impact: An analysis including information on tumour characteristics of ovarian cancer and breast cancer may provide more insight in possible links between lipid metabolism and the risk of these cancers.

  • 31. Mucci, Lorelei A.
    et al.
    Pawitan, Yudi
    Demichelis, Francesca
    Fall, Katja
    Stark, Jennifer R.
    Adami, Hans-Olov
    Andersson, Swen-Olof
    Andrén, Ove
    Eisenstein, Anna
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Huang, Wei
    Kantoff, Philip W.
    Kim, Robert
    Perner, Sven
    Stampfer, Meir J.
    Johansson, Jan-Erik
    Rubin, Mark A.
    Testing a multigene signature of prostate cancer death in the Swedish Watchful Waiting Cohort2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 7, p. 1682-8Article in journal (Refereed)
    Abstract [en]

    Although prostate cancer is a leading cause of cancer death, most men die with and not from their disease, underscoring the urgency to distinguish potentially lethal from indolent prostate cancer. We tested the prognostic value of a previously identified multigene signature of prostate cancer progression to predict cancer-specific death. The Orebro Watchful Waiting Cohort included 172 men with localized prostate cancer of whom 40 died of prostate cancer. We quantified protein expression of the markers in tumor tissue by immunohistochemistry and stratified the cohort by quintiles according to risk classification. We accounted for clinical variables (age, Gleason, nuclear grade, and tumor volume) using Cox regression and calculated receiver operator curves to compare discriminatory ability. The hazard ratio of prostate cancer death increased with increasing risk classification by the multigene model, with a 16-fold greater risk comparing highest-risk versus lowest-risk strata, and predicted outcome independent of clinical factors (P = 0.002). The best discrimination came from combining information from the multigene markers and clinical data, which perfectly classified the lowest-risk stratum where no one developed lethal disease; using the two lowest-risk groups as reference, the hazard ratio (95% confidence interval) was 11.3 (4.0-32.8) for the highest-risk group and difference in mortality at 15 years was 60% (50-70%). The combined model provided greater discriminatory ability (area under the curve = 0.78) than the clinical model alone (area under the curve = 0.71; P = 0.04). Molecular tumor markers can add to clinical variables to help distinguish lethal and indolent prostate cancer and hold promise to guide treatment decisions.

  • 32. Mucci, Lorelei A.
    et al.
    Pawitan, Yudi
    Demichelis, Francesca
    Fall, Katja
    Stark, Jennifer R.
    Adami, Hans-Olov
    Andersson, Swen-Olof
    Andrén, Ove
    Eisenstein, Anna S.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Huang, Wei
    Kantoff, Philip W.
    Perner, Sven
    Stampfer, Meir J.
    Johansson, Jan-Erik
    Rubin, Mark A.
    Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 1, p. 249-251Article in journal (Refereed)
    Abstract [en]

    Tumor molecular markers hold promise to distinguish potentially lethal from indolent prostate cancer and to guide treatment choices. A previous study identified a nine-gene molecular signature in tumors associated with prostate-specific antigen relapse after prostatectomy. We examined this molecular model in relation to prostate cancer death among 172 men with initially localized disease. We quantified protein expression of the nine genes in tumors to classify progression risk. Accounting for clinical prognostic factors, the nine-gene model did not provide discrimination to predict lethal and indolent prostate cancer.

  • 33. Nichols, Hazel B
    et al.
    Schoemaker, Minouk J
    Wright, Lauren B
    McGowan, Craig
    Brook, Mark N
    McClain, Kathleen M
    Jones, Michael E
    Adami, Hans-Olov
    Agnoli, Claudia
    Baglietto, Laura
    Bernstein, Leslie
    Bertrand, Kimberly A
    Blot, William J
    Boutron-Ruault, Marie-Christine
    Butler, Lesley
    Chen, Yu
    Doody, Michele M
    Dossus, Laure
    Eliassen, A Heather
    Giles, Graham G
    Gram, Inger T
    Hankinson, Susan E
    Hoffman-Bolton, Judy
    Kaaks, Rudolf
    Key, Timothy J
    Kirsh, Victoria A
    Kitahara, Cari M
    Koh, Woon-Puay
    Larsson, Susanna C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lund, Eiliv
    Ma, Huiyan
    Merritt, Melissa A
    Milne, Roger L
    Navarro, Carmen
    Overvad, Kim
    Ozasa, Kotaro
    Palmer, Julie R
    Peeters, Petra H
    Riboli, Elio
    Rohan, Thomas E
    Sadakane, Atsuko
    Sund, Malin
    Tamimi, Rulla M
    Trichopoulou, Antonia
    Vatten, Lars
    Visvanathan, Kala
    Weiderpass, Elisabete
    Willett, Walter C
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Sandler, Dale P
    Swerdlow, Anthony J
    The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium.2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 9, p. 1360-1369Article in journal (Refereed)
    Abstract [en]

    Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360-9. ©2017 AACR.

  • 34. Nisman, Benjamin
    et al.
    Kadouri, Luna
    Allweis, Tanir
    Maly, Bella
    Hamburger, Tamar
    Gronowitz, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Peretz, Tamar
    Increased Proliferative Background in Healthy Women with BRCA1/2 Haploinsufficiency Is Associated with High Risk for Breast Cancer2013In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 22, no 11, p. 2110-2115Article in journal (Refereed)
    Abstract [en]

    Previous studies indicated that BRCA haploinsufficiency was associated with activation of the EGF receptor (EGFR) signaling pathway and increased proliferative activity in mammary epithelial cells of healthy women. We hypothesized that these processes might be reflected in the expression of serologic soluble EGFR (sEGFR) and thymidine kinase 1 (TK1) activity, which signal the initial and final steps of the proliferative pathway, respectively. We found that healthy carriers of BRCA1/2 mutations (n = 80) showed a significantly higher TK1 activity than age-matched controls (P = 0.0003), and TK1 activity was similar in women with BRCA1 and BRCA2 mutations (P = 0.74). The sEGFR concentration was significantly higher in women with BRCA1 than in controls and BRCA2 mutation (P = 0.013 and 0.002, respectively). During follow-up, four of 80 BRCA1/2 mutation carriers developed breast cancer. These women showed a significantly higher TK1 activity and somewhat higher sEGFR concentrations than the other 76 BRCA1/2 carriers (P = 0.04 and 0.09, respectively). All tumors were negative for ovarian hormone receptors, but showed a high EGFR expression. This study was limited by the short-term follow-up (mean, 27 months; range, 5-45), which resulted in a small sample size. Women with BRCA1 and BRCA2 mutations that had undergone risk-reducing bilateral salpingo-oophorectomy (BSO) showed significantly lower sEGFR compared with those without surgery (P = 0.007 and 0.038, respectively). Larger, prospective studies are warranted to investigate whether TK1 and sEGFR measurements may be useful for identifying healthy BRCA1/2 carriers with high risk of developing breast cancer; moreover, sEGFR measurements may serve as effective tools for assessing risk before and after BSO.

  • 35. Peterlongo, Paolo
    et al.
    Chang-Claude, Jenny
    Moysich, Kirsten B.
    Rudolph, Anja
    Schmutzler, Rita K.
    Simard, Jacques
    Soucy, Penny
    Eeles, Rosalind A.
    Easton, Douglas F.
    Hamann, Ute
    Wilkening, Stefan
    Chen, Bowang
    Rookus, Matti A.
    Schmidt, MarjankaK.
    van der Baan, Frederieke H.
    Spurdle, Amanda B.
    Walker, Logan C.
    Lose, Felicity
    Maia, Ana-Teresa
    Montagna, Marco
    Matricardi, Laura
    Lubinski, Jan
    Jakubowska, Anna
    Garcia, Encarna B. Gomez
    Olopade, Olufunmilayo I.
    Nussbaum, Robert L.
    Nathanson, Katherine L.
    Domchek, Susan M.
    Rebbeck, Timothy R.
    Arun, Banu K.
    Karlan, Beth Y.
    Orsulic, Sandra
    Lester, Jenny
    Chung, Wendy K.
    Miron, Alex
    Southey, Melissa C.
    Goldgar, David E.
    Buys, Saundra S.
    Janavicius, Ramunas
    Dorfling, Cecilia M.
    van Rensburg, Elizabeth J.
    Ding, Yuan Chun
    Neuhausen, Susan L.
    Hansen, Thomas V. O.
    Gerdes, Anne-Marie
    Ejlertsen, Bent
    Jonson, Lars
    Osorio, Ana
    Martinez-Bouzas, Cristina
    Benitez, Javier
    Conway, Edye E.
    Blazer, Kathleen R.
    Weitzel, Jeffrey N.
    Manoukian, Siranoush
    Peissel, Bernard
    Zaffaroni, Daniela
    Scuvera, Giulietta
    Barile, Monica
    Ficarazzi, Filomena
    Mariette, Frederique
    Fortuzzi, Stefano
    Viel, Alessandra
    Giannini, Giuseppe
    Papi, Laura
    Martayan, Aline
    Tibiletti, Maria Grazia
    Radice, Paolo
    Vratimos, Athanassios
    Fostira, Florentia
    Garber, Judy E.
    Donaldson, Alan
    Brewer, Carole
    Foo, Claire
    Evans, D. Gareth R.
    Frost, Debra
    Eccles, Diana
    Brady, Angela
    Cook, Jackie
    Tischkowitz, Marc
    Adlard, Julian
    Barwell, Julian
    Walker, Lisa
    Izatt, Louise
    Side, Lucy E.
    Kennedy, M. John
    Rogers, Mark T.
    Porteous, Mary E.
    Morrison, Patrick J.
    Platte, Radka
    Davidson, Rosemarie
    Hodgson, Shirley V.
    Ellis, Steve
    Cole, Trevor
    Godwin, Andrew K.
    Claes, Kathleen
    Van Maerken, Tom
    Meindl, Alfons
    Gehrig, Andrea
    Sutter, Christian
    Engel, Christoph
    Niederacher, Dieter
    Steinemann, Doris
    Plendl, Hansjoerg
    Kast, Karin
    Rhiem, Kerstin
    Ditsch, Nina
    Arnold, Norbert
    Varon-Mateeva, Raymonda
    Wappenschmidt, Barbara
    Wang-Gohrke, Shan
    Bressac-de Paillerets, Brigitte
    Buecher, Bruno
    Delnatte, Capucine
    Houdayer, Claude
    Stoppa-Lyonnet, Dominique
    Damiola, Francesca
    Coupier, Isabelle
    Barjhoux, Laure
    Venat-Bouvet, Laurence
    Golmard, Lisa
    Boutry-Kryza, Nadia
    Sinilnikova, Olga M.
    Caron, Olivier
    Pujol, Pascal
    Mazoyer, Sylvie
    Belotti, Muriel
    Piedmonte, Marion
    Friedlander, Michael L.
    Rodriguez, Gustavo C.
    Copeland, Larry J.
    de la Hoya, Miguel
    Perez Segura, Pedro
    Nevanlinna, Heli
    Aittomaeki, Kristiina
    van Os, Theo A. M.
    Meijers-Heijboer, Hanne E. J.
    van der Hout, Annemarie H.
    Vreeswijk, Maaike P. G.
    Hoogerbrugge, Nicoline
    Ausems, Margreet G. E. M.
    van Doorn, Helena C.
    Collee, J. Margriet
    Olah, Edith
    Diez, Orland
    Blanco, Ignacio
    Lazaro, Conxi
    Brunet, Joan
    Feliubadalo, Lidia
    Cybulski, Cezary
    Gronwald, Jacek
    Durda, Katarzyna
    Jaworska-Bieniek, Katarzyna
    Sukiennicki, Grzegorz
    Arason, Adalgeir
    Chiquette, Jocelyne
    Teixeira, Manuel R.
    Olswold, Curtis
    Couch, Fergus J.
    Lindor, Noralane M.
    Wang, Xianshu
    Szabo, Csilla I.
    Offit, Kenneth
    Corines, Marina
    Jacobs, Lauren
    Robson, Mark E.
    Zhang, Liying
    Joseph, Vijai
    Berger, Andreas
    Singer, Christian F.
    Rappaport, Christine
    Kaulich, Daphne Geschwantler
    Pfeiler, Georg
    Tea, Muy-Kheng M.
    Phelan, Catherine M.
    Greene, Mark H.
    Mai, Phuong L.
    Rennert, Gad
    Mulligan, Anna Marie
    Glendon, Gord
    Tchatchou, Sandrine
    Andrulis, Irene L.
    Toland, Amanda Ewart
    Bojesen, Anders
    Pedersen, Inge Sokilde
    Thomassen, Mads
    Jensen, Uffe Birk
    Laitman, Yael
    Rantala, Johanna
    von Wachenfeldt, Anna
    Ehrencrona, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Askmalm, Marie Stenmark
    Borg, Ake
    Kuchenbaecker, Karoline B.
    McGuffog, Lesley
    Barrowdale, Daniel
    Healey, Sue
    Lee, Andrew
    Pharoah, Paul D. P.
    Chenevix-Trench, Georgia
    Antoniou, Antonis C.
    Friedman, Eitan
    Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers2015In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 1, p. 308-316Article in journal (Refereed)
    Abstract [en]

    Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

  • 36. Petimar, Joshua
    et al.
    Wilson, Kathryn M
    Wu, Kana
    Wang, Molin
    Albanes, Demetrius
    van den Brandt, Piet A
    Cook, Michael B
    Giles, Graham G
    Giovannucci, Edward L
    Goodman, Gary E
    Goodman, Phyllis J
    Håkansson, Niclas
    Helzlsouer, Kathy
    Key, Timothy J
    Kolonel, Laurence N
    Liao, Linda M
    Männistö, Satu
    McCullough, Marjorie L
    Milne, Roger L
    Neuhouser, Marian L
    Park, Yikyung
    Platz, Elizabeth A
    Riboli, Elio
    Sawada, Norie
    Schenk, Jeannette M
    Tsugane, Shoichiro
    Verhage, Bas
    Wang, Ying
    Wilkens, Lynne R
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ziegler, Regina G
    Smith-Warner, Stephanie A
    A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 8, p. 1276-1287Article in journal (Refereed)
    Abstract [en]

    Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear.Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model.Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index.Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer.Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR.

  • 37. Sandin, Sven
    et al.
    Hjalgrim, Henrik
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Rostgaard, Klaus
    Pukkala, Eero
    Askling, Johan
    Incidence of non-Hodgkin's lymphoma in Sweden, Denmark, and Finland from 1960 through 2003: an epidemic that was2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 7, p. 1295-1300Article in journal (Refereed)
    Abstract [en]

    Background: Reports during the early 1990s indicated non-Hodgkin's lymphoma (NHL) as one of the most rapidly increasing malignancies. More recent trends remain poorly characterized, as do the underlying reasons for NHL time trends, in particular, the effect of changes in classification and registration of lymphoproliferative malignancies. Insights into the descriptive epidemiology of NHL may shed light upon its elusive etiology. Methods: We used data from the Swedish, Danish, and Finnish national cancer registers to assess the incidences of NHL and other lymphoproliferative malignancies between 1960 and 2004. Using Poisson regression, we estimated the annual rate of change in NHL incidence per decade by sex, age, and country. Results: In Sweden, Denmark, and Finland, the NHL incidence increased in both genders and all age categories by about 4% every year up until the early 1990s. Thereafter, the incidence increased at a slower rate (ages 60-79 years), stabilized (ages 50-59 and >= 80 years), and decreased (ages 0-49 years), respectively, similarly for males and females in the three countries. Time trends of NHL were not reciprocated and explained by trends for other lymphoproliferative malignancies nor explained by trends in NHL as secondary primaries or NHL diagnosed postmortem. Conclusions: The epidemic increase of NHL has recently subsided. Changes in the classification of lymphoproliferative malignancies, or occurrence of NHL as second primaries, only offer a marginal explanation.

  • 38. Schöllkopf, Claudia
    et al.
    Smedby, Karin Ekström
    Hjalgrim, Henrik
    Rostgaard, Klaus
    Gadeberg, Ole
    Roos, Göran
    Porwit-Macdonald, Anna
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Adami, Hans-Olov
    Melbye, Mads
    Cigarette smoking and risk of non-Hodgkin's lymphoma: a population-based case-control study2005In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 14, no 7, p. 1791-1796Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiologic evidence of an association between tobacco smoking and non-Hodgkin's lymphoma has been conflicting. This may reflect that non-Hodgkin's lymphoma comprises several distinct disease entities with different etiologies, as some studies have indicated an association between smoking and follicular lymphoma. OBJECTIVE: To investigate the association between cigarette smoking and non-Hodgkin's lymphoma risk, overall and by subtype. METHODS: As part of a nationwide Danish-Swedish population-based case-control study, we interviewed 3,055 incident non-Hodgkin's lymphoma patients and 3,187 population controls. All lymphomas were uniformly classified according to the WHO classification. We used unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for the association between cigarette smoking and risk of non-Hodgkin's lymphoma. RESULTS: Cigarette smoking was not associated with the risk of non-Hodgkin's lymphoma overall (OR, 0.97; 95% CI, 0.87-1.08) nor with the major subgroups such as diffuse large B-cell lymphoma (OR, 0.94; 95% CI, 0.79-1.10), chronic lymphocytic leukemia (OR, 0.86; 95% CI, 0.72-1.02), or follicular lymphoma (OR, 1.03; 95% CI, 0.85-1.24). Female smokers were at a marginally increased risk of follicular lymphoma (OR, 1.41; 95% CI, 1.04-1.92). Men who had ever smoked had a significantly increased risk of T-cell lymphoma (OR, 1.67; 95% CI, 1.11-2.51). No dose-response association with cigarette smoking could be established for any lymphoma subgroup. CONCLUSION: We found little evidence of an association between cigarette smoking and non-Hodgkin's lymphoma risk overall. Although increased risks of follicular lymphoma in female smokers and of T-cell lymphoma in male smokers were suggested, no dose-response relationship was observed, leaving limited support for causality.

  • 39.
    Skalkidou, Alkistis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Petridou, Eleni
    Papathoma, Evgenia
    Salvanos, Heraklis
    Kedikoglou, Simos
    Chrousos, Georgios
    Trichopoulos, Dimitrios
    Determinants and consequences of major insulin-like growth factor components among full-term healthy neonates.2003In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 12, no 9, p. 860-5Article in journal (Refereed)
    Abstract [en]

    The purpose of this research was to investigate determinants of the insulin-like growth factor (IGF) system among healthy full-term newborns and explore their relation with anthropometric variables at birth. Components of the IGF system have been implicated in the pathogenesis of several forms of cancer, and perinatal events have been linked to chronic diseases in later life. Measurements of weight and length, as well as blood samples, were obtained from 331 healthy full-term newborns delivered during 1999 in Athens, Greece. Because the liver is important for IGF production, newborns were chosen to have bilirubin levels either < or = 8 mg/dl or > or = 12 mg/dl to operationally distinguish them according to the liver function. IGF-I, IGF-II, and IGF binding protein-3 were inversely associated with the presence of neonatal jaundice and blood creatinine, after controlling for blood protein levels. IGF-I increased rapidly and significantly over a period of a few days and was strongly positively associated with both birth weight and ponderal index. Newborn levels of IGF-I declined with maternal age. In comparison with first-born newborns, later-born ones had significantly higher blood IGF-I levels. We conclude that IGF-I plays a dominant role in growth during the perinatal period and that all three studied components of the IGF system are sensitive to liver and kidney function. These findings provide an insight into the processes involved in perinatal growth.

  • 40. Smedby, Karin Ekström
    et al.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Askling, Johan
    Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 11, p. 2069-2077Article in journal (Refereed)
    Abstract [en]

    Certain autoimmune and chronic inflammatory conditions, such as Sjögren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general. Likewise, it is debated whether the increased risk identified in association with some disorders pertains equally to all individuals or whether it varies among groups of patients with different phenotypic or treatment-related characteristics. It is similarly unclear to what extent the increased lymphoma occurrence is mediated through specific lymphoma subtypes. This update reviews the many findings on risks, risk levels, and lymphoma characteristics that have been presented recently in relation to a broad range of chronic inflammatory, including autoimmune, conditions. Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sjögren's syndrome. Thus, the average risk of lymphoma in RA may be composed of a markedly increased risk in those with most severe disease and little or no increase in those with mild or moderate disease. The roles of immunosuppressive therapy and EBV infection seem to be limited. Furthermore, RA, Sjögren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sjögren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma. However, there is also obvious heterogeneity in risk and risk mediators among different inflammatory diseases.

  • 41. Smedby, Karin Ekström
    et al.
    Lindgren, Cecilia M.
    Hjalgrim, Henrik
    Humphreys, Keith
    Schöllkopf, Claudia
    Chang, Ellen T.
    Roos, Göran
    Ryder, Lars P.
    Falk, Kerstin I.
    Palmgren, Juni
    Kere, Juha
    Melbye, Mads
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Adami, Hans-Olov
    Variation in DNA repair genes ERCC2, XRCC1, and XRCC3 and risk of follicular lymphoma2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 2, p. 258-265Article in journal (Refereed)
    Abstract [en]

    The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.

  • 42. Spurdle, Amanda B.
    et al.
    Marquart, Louise
    McGuffog, Lesley
    Healey, Sue
    Sinilnikova, Olga
    Wan, Fei
    Chen, Xiaoqing
    Beesley, Jonathan
    Singer, Christian F.
    Dressler, Anne-Catharine
    Gschwantler-Kaulich, Daphne
    Blum, Joanne L.
    Tung, Nadine
    Weitzel, Jeff
    Lynch, Henry
    Garber, Judy
    Easton, Douglas F.
    Peock, Susan
    Cook, Margaret
    Oliver, Clare T.
    Frost, Debra
    Conroy, Don
    Evans, D. Gareth
    Lalloo, Fiona
    Eeles, Ros
    Izatt, Louise
    Davidson, Rosemarie
    Chu, Carol
    Eccles, Diana
    Selkirk, Christina G.
    Daly, Mary
    Isaacs, Claudine
    Stoppa-Lyonnet, Dominique
    Sinilnikova, Olga M.
    Buecher, Bruno
    Belotti, Muriel
    Mazoyer, Sylvie
    Barjhoux, Laure
    Verny-Pierre, Carole
    Lasset, Christine
    Dreyfus, Helene
    Pujol, Pascal
    Collonge-Rame, Marie-Agnes
    Rookus, Matti A.
    Verhoef, Senno
    Kriege, Mieke
    Hoogerbrugge, Nicoline
    Ausems, Margreet G. E. M.
    van Os, Theo A.
    Wijnen, Juul
    Devilee, Peter
    Meijers-Heijboer, Hanne E. J.
    Blok, Marinus J.
    Heikkinen, Tuomas
    Nevanlinna, Heli
    Jakubowska, Anna
    Lubinski, Jan
    Huzarski, Tomasz
    Byrski, Tomasz
    Durocher, Francine
    Couch, Fergus J.
    Lindor, Noralane M.
    Wang, Xianshu
    Thomassen, Mads
    Domchek, Susan
    Nathanson, Kate
    Caligo, M. A.
    Jernström, Helena
    Liljegren, Annelie
    Ehrencrona, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Karlsson, Per
    Ganz, Patricia A.
    Olopade, Olufunmilayo I.
    Tomlinson, Gail
    Neuhausen, Susan
    Antoniou, Antonis C.
    Chenevix-Trench, Georgia
    Rebbeck, Timothy R.
    Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 5, p. 1032-1038Article in journal (Refereed)
    Abstract [en]

    Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk.

  • 43. Sundström, Karin
    et al.
    Eloranta, Sandra
    Sparén, Pär
    Dahlström, Lisen Arnheim
    Gunnell, Anthony
    Lindgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Palmgren, Juni
    Ploner, Alexander
    Sanjeevi, Carani B.
    Melbye, Mads
    Dillner, Joakim
    Adami, Hans-Olov
    Ylitalo, Nathalie
    Prospective Study of Human Papillomavirus (HPV) Types, HPV Persistence, and Risk of Squamous Cell Carcinoma of the Cervix2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 10, p. 2469-2478Article in journal (Refereed)
    Abstract [en]

    Background: The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear. Methods: In two prospective nested case-control series among women participating in cytologic screening in Sweden, we collected 2,772 cervical smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell carcinoma (SCC), and individually matched controls. All smears were tested for HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). Results: The presence of HPV16/18 in the first smear was associated with 8.5-fold (95% CI, 5.3-13.7) and 18.6-fold (95% CI, 9.0-38.9) increased risks of CIS and SCC, respectively, compared with women negative for HPV. Infection with other HRHPV types in the first smear was also associated with significantly increased risks for both CIS and SCC. Persistence of HPV16 infection conferred a RR of 18.5 (95% CI, 6.5-52.9) for CIS and 19.5 (95% CI, 4.7-81.7) for SCC. The HPV16/18 attributable risk proportion was estimated at 30% to 50% for CIS, and 41% to 47% for SCC. Other HRHPV types also conferred significant proportions. Conclusions: Our large population-based study provides quantification of risks for different HPV types and prospective evidence that non-16/18 HRHPV types increase the risk for future cervical cancer. Impact: This study gives further insights into cervical cancer risk stratification with implications for HPV-based prevention strategies.

  • 44. Terry, Paul
    et al.
    Bergkvist, Leif
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Wolk, Alicja
    No association between fat and fatty acids intake and risk of colorectal cancer2001In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 10, no 8, p. 913-914Article in journal (Refereed)
  • 45. Titus-Ernstoff, Linda
    et al.
    Månsson-Brahme, Eva
    Thörn, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Yuen, Jonathan
    Dain, Bradley
    Ding, Jiao
    Baron, John
    Adami, Hans-Olov
    Factors associated with atypical nevi: A population-based study1998In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 7, no 3, p. 207-210Article in journal (Refereed)
    Abstract [en]

    We conducted a case-control study to identify factors associated with the presence of clinically atypical nevi. Potential participants were selected, using a two-staged sampling scheme, from a population-based cohort of 50,000 Swedish women who had responded to a previous health survey questionnaire. Of 500 women sampled for study recruitment, 400 (80%) agreed to participate. Study participants underwent a physician-conducted skin examination, which identified 130 women who had at least one clinically atypical nevus (cases) and 270 women without these lesions (controls). The physician-conducted skin examination also assessed women for benign nevus counts; other risk factor information was based upon responses to a health survey questionnaire. We found a strong and highly statistically significant relationship between number of benign nevi and the presence of at least one clinically atypical nevus (P < 0.0001). Women with 100 or more benign nevi had a 26-fold increased likelihood of having an atypical nevus. We noted statistically significant interactions between number of benign nevi and other factors of interest; thus, the results are reported separately for women with low (<50) or high (> or =50) counts of benign nevi. Among women with low counts of benign nevi, the likelihood of having an atypical nevus increased with degree of freckling; there was also a suggested role for early sun exposure. Among women with high counts of benign nevi, difficulty tanning and lack of peeling sunburns between ages 10 and 19 appeared to increase the likelihood of case status; our data also suggested an inverse relationship between parity and atypical nevi in this subgroup.

  • 46. van Hemelrijck, Mieke
    et al.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Garmo, Hans
    Hammar, Niklas
    Walldius, Göran
    Binda, Elisa
    Lambe, Mats
    Jungner, Ingmar
    Association between levels of C-reactive protein and leukocytes and cancer: three repeated measurements in the Swedish AMORIS study2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 3, p. 428-437Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To study levels of C-reactive protein (CRP) and leukocytes, as inflammatory markers, in the context of cancer risk.

    METHODS:

    From the Apolipoprotein MOrtality RISk (AMORIS) study, we selected 102,749 persons with one measurement and 9,273 persons with three repeated measurements of CRP and leukocytes. Multivariate Cox proportional hazards regression was applied to categories of CRP (<10, 10-15, 15-25, 25-50, >50 g/L) and quartiles of leukocytes. An inflammation-based predictive score (IPS) indicated whether someone had CRP levels of more than 10 mg/L combined with leukocytes of more than 10×10(9)/L. Reverse causality was assessed by excluding those with less than 3, 5, or 7 years of follow-up. To analyze repeated measurements of CRP and leukocytes, the repeated IPS (IPSr) was calculated by adding the IPS of each measurement.

    RESULTS:

    In the cohort with one measurement, there was a positive trend between CRP and risk of developing cancer, with the lowest category being the 0.99 (0.92-1.06), 1.28 (1.11-1.47), 1.27 (1.09-1.49), and 1.22 (1.01-1.48) for the second to fifth categories, respectively. This association disappeared when excluding those with follow-up of less than 3, 5, or 7 years. The association between leukocytes and cancer was slightly stronger. In the cohort with repeated measurements, the IPSr was strongly associated with cancer risk: 1.87 (1.33-2.63), 1.51 (0.56-4.06), and 4.46 (1.43-13.87) for IPSr=1, 2, and 3 compared with IPSr=0. The association remained after excluding those with follow-up of less than 1 year.

    CONCLUSIONS AND IMPACT:

    Our large, prospective cohort study adds evidence for a link between inflammatory markers and cancer risk by using repeated measurements and ascertaining reverse causality.

  • 47. Vandrovcova, Jana
    et al.
    Lagerstedt-Robinsson, Kristina
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Lindblom, Annika
    Somatic BRAF-V600E Mutations in Familial Colorectal Cancer2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 11, p. 2270-2273Article in journal (Refereed)
    Abstract [en]

    The BRAF gene is mutated in 4% to 12% of unselected colorectal cancers, particularly those with high microsatellite instability and in premalignant lesions, such as serrated adenomas and hyperplastic polyps. However, it has been shown that activating BRAF mutations are almost never found in tumors from hereditary nonpolyposis colorectal cancer patients. To evaluate the role of oncogenic BRAF mutations in non-hereditary nonpolyposis colorectal cancer/ non-familial adenomatous polyposis familial colorectal cancer, we did a mutation screening of the most common BRAT mutation, the V600E mutation, in 194 colorectal tumors from patients with a positive family history of the disease. The BRAF-V600E mutation was identified in 100% (8 of 8) of microsatellite-unstable tumors and in 9.7% (18 of 186) of microsatellite-stable tumors. Interestingly, families with extracolonic tumors showed a much higher mutation frequency (17.5%) compared with families with colonic cancer only (3.5%; P = 0.009). In addition, we studied colonoscopic results from 448 family members who had been under colonoscopic surveillance for several years. Subjects from families where the V600E mutation was identified had less adenomas compared with those from families where no BRAT mutation had been found (odds ratio, 8.5; 95% confidence interval, 1.1-64.6). These findings indicate that adenomas might be less important in the cancer development in the group of families with BRAF-V600E mutations and indirectly support a previous hypothesis that tumors might develop through the yperplastic polyp-serrated adenoma pathway. In conclusion, our results suggest that BRAF-V600E mutations are mainly involved in colorectal. cancer families characterized by an increased risk of other common malignancies.

  • 48.
    Ward, Heather A.
    et al.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Wark, Petra A.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Muller, David C.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Steffen, Annika
    German Inst Human Nutr Potsdam Rehbruke, Dept Epidemiol, Nuthetal, Germany..
    Johansson, Mattias
    Int Agcy Res Canc IARC WHO, Lyon, France.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Norat, Teresa
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Gunter, Marc J.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Int Agcy Res Canc IARC WHO, Lyon, France..
    Overvad, Kim
    Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus, Denmark.;Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark..
    Dahm, Christina C.
    Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus, Denmark..
    Halkjaer, Jytte
    Danish Canc Soc Res Ctr Diet Genes & Environm, Copenhagen, Denmark..
    Tojonneland, Anne
    Danish Canc Soc Res Ctr Diet Genes & Environm, Copenhagen, Denmark..
    Boutron-Ruault, Marie-Christine
    Univ Paris Sud, UVSQ, INSERM, Univ Paris Saclay,Generat & Hlth, Villejuif, France.;Gustave Roussy, Villejuif, France..
    Fagherazzi, Guy
    Univ Paris Sud, UVSQ, INSERM, Univ Paris Saclay,Generat & Hlth, Villejuif, France.;Gustave Roussy, Villejuif, France..
    Mesrine, Sylvie
    Univ Paris Sud, UVSQ, INSERM, Univ Paris Saclay,Generat & Hlth, Villejuif, France.;Gustave Roussy, Villejuif, France..
    Brennan, Paul
    Int Agcy Res Canc IARC WHO, Lyon, France..
    Freisling, Heinz
    Int Agcy Res Canc IARC WHO, Lyon, France..
    Li, Kuanrong
    Int Agcy Res Canc IARC WHO, Lyon, France..
    Kaaks, Rudolf
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece.;Acad Athens, Bur Epidemiol Res, Athens, Greece..
    Lagiou, Pagona
    Acad Athens, Bur Epidemiol Res, Athens, Greece.;Univ Athens, Med Sch, Dept Hyg Epidemiol & Med Stat, Athens, Greece.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Panico, Salavatore
    Univ Naples Federico II, Sect Endocrinol, Dept Clin Med & Surg, Naples, Italy..
    Grioni, Sara
    Fdn IRCCS Natl Canc Inst, Epidemiol & Prevent Unit, Milan, Italy..
    Tumino, Rosario
    ASP Ragusa, Civic MP Arezzo Hosp, Canc Registry & Histopathol Unit, Ragusa, Italy..
    Vineis, Paolo
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;HuGeF Fdn, Turin, Italy..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy..
    Peeters, Petra H. M.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands..
    Bueno-de-Mesquita, H. Bas.
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands..
    Weiderpass, Elisabete
    UiT Arct Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway.;Inst Population Based Canc Res, Canc Registry Norway, Oslo, Norway.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland..
    Agudo, Antonio
    Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain..
    Ramon Quiros, Jose
    Publ Hlth Directorate, Asturias, Spain.;IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain..
    Larranaga, Nerea
    Publ Hlth Div Gipuzkoa BIODONOSTIA, Basque Reg Hlth Dept, Donostia San Sebastian, Spain.;CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Ardanaz, Eva
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Navarre Publ Hlth Inst, Pamplona, Spain..
    Maria Huerta, Jose
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain..
    Sanchez, Maria-Jose
    CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.;Univ Cartuja, Res Inst Biosanitary Granada, Andalucian Sch Publ Hlth, Granada, Spain..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Johansson, Ingegerd
    Umea Univ, Dept Odontol, Umea, Sweden..
    Westin, Ulla
    Lund Univ, Dept Otorhinolaryngol, Univ Hosp, Ear Nose & Throat Dept, Malmo, Sweden..
    Wallstrom, Peter
    Lund Univ, Dept Clin Sci, Nutr Epidemiol Res Grp, Skane Univ Hosp, Malmo, Sweden..
    Bradbury, Kathryn E.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Met Sci, MRC Epidemiol Unit, Cambridge, England..
    Khaw, Kay-Tee
    Univ Cambridge, Addenbrookes Hosp, Clin Gerontol Unit, Cambridge, England..
    Pearson, Clare
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England.;Publ Hlth England, Canc Res UK, London, England..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruke, Dept Epidemiol, Nuthetal, Germany..
    Riboli, Elio
    Imperial Coll London, Sch Publ Hlth, St Marys Campus, London, England..
    Measured Adiposity in Relation to Head and Neck Cancer Risk in the European Prospective Investigation into Cancer and Nutrition2017In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 6, p. 895-904Article in journal (Refereed)
    Abstract [en]

    Background: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer. However, most studies have used self-reported anthropometry which is prone to error. Methods: Among 363,094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of head and neck cancer. Head and neck cancer risk was examined in relation to body mass index (BMI) [lean: <22.5 kg/m(2), normal weight (reference): 22.5-24.9 kg/m(2), overweight 25-29.9 kg/m(2), obese: >= 30 kg/m(2)], waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) using Cox proportional hazards models. Results: Among men, a BMI <22.5 kg/m(2) was associated with higher head and neck cancer risk [HR 1.62; 95% confidence interval (CI), 1.23-2.12)]; BMI was not associated with head and neck cancer among women. WC and WHR were associated with greater risk of head and neck cancer among women (WC per 5 cm: HR, 1.08; 95% CI, 1.02-1.15; WHR per 0.1 unit: HR, 1.64; 95% CI, 1.38-1.93). After stratification by smoking status, the association for WHR was present only among smokers (P-interaction = 0.004). Among men, WC and WHR were associated with head and neck cancer only upon additional adjustment for BMI (WC per 5 cm: HR 1.16; 95% CI, 1.07-1.26; WHR per 0.1 unit: HR, 1.42; 95% CI, 1.21-1.65). Conclusions: Central adiposity, particularly among women, may have a stronger association with head and neck cancer risk than previously estimated.

  • 49. Wedrén, Sara
    et al.
    Magnusson, Cecilia
    Humphreys, Keith
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stiger, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Branting, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Persson, Ingemar
    Baron, John
    Weiderpass, Elisabete
    Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer2007In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 16, no 9, p. 1775-1783Article in journal (Refereed)
    Abstract [en]

    We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAG(n) and VDR A(n) genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (</=21 or >/=22 repeats for AR and </=18 or >/=19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAG(n) repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with >/=20 repeats. Women carrying two VDR alleles with <21 A(n) were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated.

1 - 49 of 49
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