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Holmberg, Lars
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Publications (10 of 198) Show all publications
Yiu, A., Van Hemelrijck, M., Garmo, H., Holmberg, L., Malmström, H., Lambe, M., . . . Wulaningsih, W. (2017). Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study. OncoTarget, 8(26), 42332-42342.
Open this publication in new window or tab >>Circulating uric acid levels and subsequent development of cancer in 493,281 individuals: findings from the AMORIS Study
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 26, 42332-42342 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: Serum uric acid has been suggested to be associated with cancer risk. We aimed to study the association between serum uric acid and cancer incidence in a large Swedish cohort.

Results: A positive association was found between uric acid levels and overall cancer risk, and results were similar with adjustment for glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and 1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma skin, and other cancers in men and of head and neck and other cancers in women. An inverse association was observed for pulmonary and central nervous system (CNS) cancers in men and breast, lymphatic and haematological, and CNS malignancies in women.

Materials and Methods: We included 493,281 persons aged 20 years and older who had a measurement of serum uric acid and were cancer-free at baseline in the AMORIS study. Multivariable Cox proportional hazards regression was used to investigate sex-specific quartiles of serum uric acid in relation to cancer risk in men and women. Analysis was further adjusted for serum glucose, triglycerides and, where available, BMI. Site-specific analysis was performed for major cancers.

Conclusions: Altered uric acid levels were associated with risk of overall and some specific cancers, further indicating the potential role of uric acid metabolism in carcinogenesis.

Keyword
uric acid, cancer, prospective study
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-332205 (URN)10.18632/oncotarget.16198 (DOI)000405493400049 ()28418841 (PubMedID)
Available from: 2017-10-26 Created: 2017-10-26 Last updated: 2017-11-29Bibliographically approved
Häggström, C., Liedberg, F., Hagberg, O., Aljabery, F., Ströck, V., Hosseini, A., . . . Holmberg, L. (2017). Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe). BMJ Open, 7(9), Article ID e016606.
Open this publication in new window or tab >>Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)
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2017 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, e016606Article in journal (Refereed) Published
Abstract [en]

Purpose: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe).

Participants: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death.

Findings to date: Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival.

Future plans: The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-337759 (URN)10.1136/bmjopen-2017-016606 (DOI)000412650700144 ()28963292 (PubMedID)
Funder
Swedish Cancer Society, CAN 2013/472
Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2018-01-12Bibliographically approved
Lawler, K., Papouli, E., Naceur-Lombardelli, C., Mera, A., Ougham, K., Tutt, A., . . . Purushotham, A. (2017). Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study. Breast Cancer Research, 19, Article ID 113.
Open this publication in new window or tab >>Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study
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2017 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 19, 113Article in journal (Refereed) Published
Abstract [en]

Background: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.

Methods: A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Whole-genome expression profiles were obtained using whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE) samples. A systematic protocol was developed for handling FFPE samples together with stringent data quality controls to identify robust expression profiling data. A panel of published and novel gene sets were tested for association with these specific patterns of metastatic spread and odds ratios (ORs) were calculated.

Results: Metasynchronous metastasis to bone and viscera was found in all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined receptor status and specific IntClust subgroups were risk factors for visceral-only or bone-only first metastases. Among gene modules, those related to proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3 (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV) was identified in estrogen-receptor-positive breast cancers with metasynchronous metastasis to bone and viscera (area under the curve = 0.77), and its expression increased the risk of bone and visceral metasynchronous spread in this population. BV was further orthogonally validated with NanoString nCounter in primary breast cancers, and was reproducible in their matched lymph nodes metastases and an external cohort.

Conclusion: This case-control study of WG-DASL global expression profiles from FFPE tumour samples, after careful quality control and RNA selection, revealed that gene modules in the primary tumour have differing risks for clinical patterns of metasynchronous first metastases. Moreover, a novel gene module was identified as a putative risk factor for metasynchronous bone and visceral first metastatic spread, with potential implications for disease monitoring and treatment planning.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keyword
Breast cancer, Metasynchronous metastases, Gene expression pattern
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337331 (URN)10.1186/s13058-017-0881-y (DOI)000412892700001 ()29029636 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 259881
Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-01-03Bibliographically approved
Grönberg, M., Ahlin, C., Naeser, Y., Tiensuu Janson, E., Holmberg, L. & Fjällskog, M.-L. (2017). Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer. PLoS ONE, 12(4), Article ID e0176059.
Open this publication in new window or tab >>Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, e0176059Article in journal (Refereed) Published
Abstract [en]

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size <= 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

Keyword
Hormone releasing hormone, food intake, cell-lines, cyclin-A, expression, obestatin, stomach, identification, secretion, receptor
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-322807 (URN)10.1371/journal.pone.0176059 (DOI)000399875200066 ()28419141 (PubMedID)
Available from: 2017-09-13 Created: 2017-09-13 Last updated: 2017-11-29Bibliographically approved
Grönberg, M., Ahlin, C., Naeser, Y., Tiensuu Janson, E., Holmberg, L. & Fjällskog, M.-L. (2017). Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer. PLoS ONE, 12(4), Article ID e0176059.
Open this publication in new window or tab >>Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, e0176059Article in journal (Refereed) Published
Abstract [en]

Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-323164 (URN)10.1371/journal.pone.0176059 (DOI)28419141 (PubMedID)
Available from: 2017-06-02 Created: 2017-06-02 Last updated: 2017-11-29Bibliographically approved
Catto, J. W. F., Blazeby, J. M., Holmberg, L., Hamdy, F. C. & Brown, J. (2017). In Defense of Randomized Clinical Trials in Surgery: Let Us Not Forget Archie Cochrane's Legacy. European Urology, 71(5), 820-821.
Open this publication in new window or tab >>In Defense of Randomized Clinical Trials in Surgery: Let Us Not Forget Archie Cochrane's Legacy
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2017 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, no 5, 820-821 p.Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2017
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-320961 (URN)10.1016/j.eururo.2016.12.029 (DOI)000397773300038 ()28087094 (PubMedID)
Available from: 2017-04-28 Created: 2017-04-28 Last updated: 2017-04-28Bibliographically approved
Wickberg, A., Magnuson, A., Holmberg, L. & Liljegren, G. (2017). Luminal B/HER2-negative-like subtype is a predictor for local recurrence after breast-conserving surgery and shows no interaction with randomization. Breast, 32, S107-S107.
Open this publication in new window or tab >>Luminal B/HER2-negative-like subtype is a predictor for local recurrence after breast-conserving surgery and shows no interaction with randomization
2017 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 32, S107-S107 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
CHURCHILL LIVINGSTONE, 2017
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-320964 (URN)000397930400281 ()
Available from: 2017-04-28 Created: 2017-04-28 Last updated: 2017-04-28Bibliographically approved
Häggström, C., Van Hemelrijck, M., Zethelius, B., Robinson, D., Grundmark, B., Holmberg, L., . . . Stattin, P. (2017). Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer. International Journal of Cancer, 140(3), 611-617.
Open this publication in new window or tab >>Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer
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2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 3, 611-617 p.Article in journal (Refereed) Published
Abstract [en]

Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD=9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD=3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR=0.85, 95% CI=0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR=0.96, 95% CI=0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR=0.73, 95% CI=0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR=1.11, 95% CI=0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.

What's new? Although Type 2 diabetes mellitus (T2DM) increases the risk of several cancers, multiple studies point toward a significantly inverse relationship between T2DM and prostate cancer risk in men. Use of the anti-diabetic drug metformin is suspected of underlying the association. In this prospective study in Sweden, however, metformin failed to decrease the risk of prostate cancer. By comparison, risk was decreased in association with the use of insulin or sulfonylurea. These findings add some support to an inverse association between T2DM severity and prostate cancer risk.

Keyword
prostate cancer, Type 2 diabetes mellitus, metformin, cohort study, survival analysis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-314400 (URN)10.1002/ijc.30480 (DOI)000390702500013 ()
Funder
Swedish Research Council, 825-2012-5047Swedish Cancer Society, 2009/941, 11 0471
Available from: 2017-02-08 Created: 2017-02-02 Last updated: 2017-11-29Bibliographically approved
Bosco, C., Garmo, H., Adolfsson, J., Stattin, P., Holmberg, L., Nilsson, P., . . . Van Hemelrijck, M. (2017). Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events. International Journal of Radiation Oncology, Biology, Physics, 97(5), 1026-1031.
Open this publication in new window or tab >>Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events
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2017 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 97, no 5, 1026-1031 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa).

Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age-and county-matched comparison cohort of PCa-free men (n = 46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression.

Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis.

Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-324345 (URN)10.1016/j.ijrobp.2017.01.218 (DOI)000401128500026 ()28332985 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-5047Swedish Cancer Society
Available from: 2017-06-15 Created: 2017-06-15 Last updated: 2017-06-15Bibliographically approved
Ghuan, S., Van Hemelrijck, M., Garmo, H., Holmberg, L., Malmström, H., Lambe, M., . . . Wulaningsih, W. (2017). Serum inflammatory markers and colorectal cancer risk and survival. British Journal of Cancer, 116(10), 1358-1365.
Open this publication in new window or tab >>Serum inflammatory markers and colorectal cancer risk and survival
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2017 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, no 10, 1358-1365 p.Article in journal (Refereed) Published
Abstract [en]

Background: Inflammation has been linked with development of some cancers. We investigated systemic inflammation in relation to colorectal cancer incidence and subsequent survival using common serum inflammatory markers

Design: A cohort of men and women aged 20 years and older in greater Stockholm area with serum C-reactive protein (CRP) and albumin measured between 1986 and 1999 were included (n-325 599). A subset of these had baseline measurements of haptoglobin and leukocytes. Multivariable Cox regression was performed to assess risk of colorectal cancer by levels of inflammatory markers, adjusting for potential confounders. Analyses were stratified by circulating glucose, total cholesterol and triglycerides. Overall and CRC-specific death following diagnosis were assessed as secondary outcomes.

Results: A total of 4764 individuals were diagnosed with colorectal cancer. A positive association between haptoglobin and colorectal cancer incidence was found (hazard ratio (HR): 1.17; 95% CI: 1.06-1.28). A positive association was also observed with leukocytes (HR: 1.21; 95% CI: 1.03-1.42). No evidence of association was noted between CRP and colorectal cancer risk. Higher risks of all-cause death were seen with haptoglobin and leukocytes levels. Higher haptoglobin levels were linked with an increased risk of colorectal cancer death (HR: 1.19; 95% CI: 1.01-1.41).

Conclusions: Prediagnostic systemic inflammation may impact colorectal cancer incidence and survival; therefore, prompting investigations linking inflammatory pathways preceding colorectal cancer with disease severity and progression.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
Keyword
colorectal cancer, CRP, haptoglobin, leukocytes, albumin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-325335 (URN)10.1038/bjc.2017.96 (DOI)000401012500014 ()
Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2017-06-30Bibliographically approved
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