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Publications (10 of 190) Show all publications
Sidahmed, E., Freedland, S. J., Wang, M., Wu, K., Albanes, D., Barnett, M., . . . Smith-Warner, S. A. (2025). Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies. Journal of the Academy of Nutrition and Dietetics, 125(1), 11-23.e22
Open this publication in new window or tab >>Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies
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2025 (English)In: Journal of the Academy of Nutrition and Dietetics, ISSN 2212-2672, E-ISSN 2212-2680, Vol. 125, no 1, p. 11-23.e22Article in journal (Refereed) Published
Abstract [en]

Background

Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited.

Objective

The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC.

Design

The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study.

Participants/setting

There were 842149 men followed for up to 9 to 22 years between 1985 and 2009 across studies.

Main outcome measures

The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score >= 8 or poorly differentiated/undifferentiated) and PC mortality.

Statistical analysis performed

Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models.

Results

Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P <= .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366).

Conclusions

Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.
Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Cohort studies, Dietary fi ber, Grains, Pooled analysis, Prostate cancer, Supplementary materials:
National Category
Cancer and Oncology Nutrition and Dietetics Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:uu:diva-548608 (URN)10.1016/j.jand.2024.04.006 (DOI)001394129100001 ()38636793 (PubMedID)2-s2.0-85194915395 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2025-02-04 Created: 2025-02-04 Last updated: 2025-02-04Bibliographically approved
Ibsen, D. B., Chiu, Y.-H., Gemes, K. & Wolk, A. (2024). Hypothetical 22-Year Intervention With the Dietary Approaches to Stop Hypertension and Risk of Heart Failure in a General Population. American Journal of Epidemiology, 193(1), 96-106
Open this publication in new window or tab >>Hypothetical 22-Year Intervention With the Dietary Approaches to Stop Hypertension and Risk of Heart Failure in a General Population
2024 (English)In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 193, no 1, p. 96-106Article in journal (Refereed) Published
Abstract [en]

We used design principles of target trial methodology to emulate the effect of sustained adherence to the Dietary Approaches to Stop Hypertension (DASH) diet on the 22-year risk of heart failure. Women and men aged 45-83 years without previous heart failure, who answered questionnaires in 1997 from the Swedish Mammography Cohort and the Cohort of Swedish Men, were eligible. Follow-up questionnaires were sent in 2008-2009. Incidence of heart failure was ascertained using the Swedish Patient Register, updated until December 31, 2019. The parametric g-formula was used to estimate the 22-year risk of heart failure under sustained adherence to a population-adapted DASH diet compared with no intervention. Intakes before 1997 for before-baseline adjustment was available only for women. In total, 31,238 women and 34,939 men were eligible. The 22-year risk of heart failure was 14.5% with long-term adherence to the DASH diet compared with 15.2% with no intervention (risk difference = -0.7%, 95% confidence interval: 1.6, 0.0%) in women and correspondingly in men 15.3% vs. 16.2% (risk difference = -0.9%, 95% confidence interval: -1.6, -0.2%). Our hypothetical intervention suggests that sustained adherence to the population-adapted DASH diet may reduce risk of heart failure in middle-aged and elderly Swedish women and men.
Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
cardiovascular disease, DASH diet, hypothetical trial, nutrition, prevention, public health
National Category
Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:uu:diva-529822 (URN)10.1093/aje/kwad181 (DOI)001112149800001 ()37656615 (PubMedID)
Funder
Swedish Research Council, 2015-02302Swedish Research Council, 2018-03028Swedish Research Council Formas, 2016-00308Swedish Research Council, 2017-00644Swedish Research Council
Available from: 2024-06-10 Created: 2024-06-10 Last updated: 2025-02-10Bibliographically approved
Dareng, E. O., Coetzee, S. G., Tyrer, J. P., Peng, P.-C., Rosenow, W., Chen, S., . . . Gayther, S. A. (2024). Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions. American Journal of Human Genetics, 111(6), 1061-1083
Open this publication in new window or tab >>Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions
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2024 (English)In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 111, no 6, p. 1061-1083Article in journal (Refereed) Published
Abstract [en]

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10−8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10−5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.
Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
epithelial ovarian cancer risk, GWAS, fine mapping, functional mechanisms
National Category
Medical Genetics and Genomics Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-540811 (URN)10.1016/j.ajhg.2024.04.011 (DOI)001287627100001 ()38723632 (PubMedID)
Funder
NIH (National Institutes of Health)
Available from: 2024-10-23 Created: 2024-10-23 Last updated: 2025-02-10Bibliographically approved
Watts, E. L., Gonzales, T. I., Strain, T., Saint-Maurice, P. F., Bishop, D. T., Chanock, S. J., . . . Riboli, E. (2024). Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study. British Journal of Cancer, 130(1), 114-124
Open this publication in new window or tab >>Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
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2024 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 130, no 1, p. 114-124Article in journal (Refereed) Published
Abstract [en]

BackgroundThe association of fitness with cancer risk is not clear.MethodsWe used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.ResultsAfter a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2 & sdot;min-1 & sdot;kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2 & sdot;min-1 & sdot;kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.DiscussionHigher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention.
Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-540310 (URN)10.1038/s41416-023-02489-3 (DOI)001118474500002 ()38057395 (PubMedID)
Available from: 2024-10-15 Created: 2024-10-15 Last updated: 2024-10-15Bibliographically approved
Middha, P. K., Wang, X., Behrens, S., Bolla, M. K., Wang, Q., Dennis, J., . . . Chang-Claude, J. (2023). A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry. Breast Cancer Research, 25(1), Article ID 93.
Open this publication in new window or tab >>A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
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2023 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 25, no 1, article id 93Article in journal (Refereed) Published
Abstract [en]

Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Breast cancer, Gene-environment interactions, Genetic epidemiology, European ancestry
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-511959 (URN)10.1186/s13058-023-01691-8 (DOI)001045490000001 ()37559094 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, R01CA192393EU, European Research Council, 199600Swedish Cancer Society, 702892-BR ISwedish Research CouncilSwedish Cancer Society, HHSN268201100001CSwedish Cancer Society, HHSN268201100002C
Available from: 2023-10-31 Created: 2023-10-31 Last updated: 2023-10-31Bibliographically approved
Zanti, M., O'Mahony, D. G., Parsons, M. T., Li, H., Dennis, J., Aittomakkiki, K., . . . Michailidou, K. (2023). A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2. Human Mutation, 2023, Article ID 9961341.
Open this publication in new window or tab >>A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2
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2023 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 2023, article id 9961341Article in journal (Refereed) Published
Abstract [en]

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity-findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Place, publisher, year, edition, pages
John Wiley & Sons, 2023
National Category
Cancer and Oncology Medical Genetics and Genomics
Identifiers
urn:nbn:se:uu:diva-521211 (URN)10.1155/2023/9961341 (DOI)001091490300001 ()
Funder
EU, Horizon 2020, 634935EU, Horizon 2020, 633784EU, FP7, Seventh Framework Programme, 223175 (HEALTH-F2-2009-223175)Karolinska InstituteSwedish Cancer Society, CAN 2018/675Swedish Research Council, VR 2017-00644Swedish Research Council, PBZ_KBN_122/P05/2004Swedish Cancer Society
Available from: 2024-01-19 Created: 2024-01-19 Last updated: 2025-02-10Bibliographically approved
Mueller, S. H., Lai, A. G., Valkovskaya, M., Michailidou, K., Bolla, M. K., Wang, Q., . . . Kuchenbaecker, K. B. (2023). Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry. Genome Medicine, 15, Article ID 7.
Open this publication in new window or tab >>Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
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2023 (English)In: Genome Medicine, E-ISSN 1756-994X, Vol. 15, article id 7Article in journal (Refereed) Published
Abstract [en]

Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.

Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.

Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.

Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Breast cancer susceptibility, Diverse ancestry, Rare variants, Gene regulation, Genome-wide association study
National Category
Medical Genetics and Genomics
Identifiers
urn:nbn:se:uu:diva-498948 (URN)10.1186/s13073-022-01152-5 (DOI)000928030200002 ()36703164 (PubMedID)
Funder
EU, European Research Council, 948561EU, Horizon 2020, 634935EU, Horizon 2020, 633,784EU, FP7, Seventh Framework Programme, 223,175 (HEALTH-F2-2009-223,175)EU, Horizon 2020, 634,935Karolinska InstituteSwedish Cancer SocietySwedish Research Council, VR 2017-00,644Wellcome trust, v203477/Z/16/ZStockholm County CouncilKing Gustaf V Jubilee FundBerth von Kantzows foundationMrs. Berta Kamprad's Cancer Foundation
Available from: 2023-03-22 Created: 2023-03-22 Last updated: 2025-02-10Bibliographically approved
Wang, A., Shen, J., Rodriguez, A. A., Saunders, E. J., Chen, F., Janivara, R., . . . Haiman, C. A. (2023). Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nature Genetics, 55(12), 2065-2074
Open this publication in new window or tab >>Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
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2023 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 55, no 12, p. 2065-2074Article in journal (Refereed) Published
Abstract [en]

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
Place, publisher, year, edition, pages
Springer Nature, 2023
National Category
Medical Genetics and Genomics Clinical Medicine Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-524994 (URN)10.1038/s41588-023-01534-4 (DOI)001142400800001 ()37945903 (PubMedID)2-s2.0-85176259299 (Scopus ID)
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2025-04-04Bibliographically approved
Khalili, H., Hakansson, N., Casey, K., Lopes, E., Ludvigsson, J. F., Chan, A. T., . . . Wolk, A. (2023). Diet Quality and Risk of Older-onset Crohn's Disease and Ulcerative Colitis. Journal of Crohn's & Colitis, 17(5), 746-753
Open this publication in new window or tab >>Diet Quality and Risk of Older-onset Crohn's Disease and Ulcerative Colitis
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2023 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no 5, p. 746-753Article in journal (Refereed) Published
Abstract [en]

Background

We aimed to assess the relationship between diet quality and risk of older-onset Crohn’s disease [CD] and ulcerative colitis [UC].

Methods

We conducted a prospective cohort study of 83 147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaires to calculate adherence scores to multiple derived healthy diet patterns: Alternate Healthy Eating Index [AHEI], Healthy Eating Index-2015 [HEI-2015], Healthful Plant-Based Diet Index [HPDI], and modified Mediterranean Diet Score [mMED] at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modelling to estimate the adjusted hazard ratios [HRs] and 95% confidence intervals [CIs].

Results

Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest with the lowest quartiles, the adjusted HRs of CD were 0.73 [95% CI, 0.48, 1.12, ptrend = 0.123] for AHEI; 0.90 [0.57, 1.41, ptrend = 0.736] for HEI 2015; 0.52 [95% CI 0.32, 0.85, ptrend = 0.011] for HPDI; and 0.58 [95% CI 0.32, 1.06, ptrend = 0.044] for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC.

Conclusions

We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals’ food preferences and traditions in designing future prevention strategies for IBD.
Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
Crohn's disease, diet quality, epidemiology, nutrition, ulcerative colitis
National Category
Gastroenterology and Hepatology Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-512525 (URN)10.1093/ecco-jcc/jjac184 (DOI)000915090300001 ()36521021 (PubMedID)
Funder
Swedish Research Council, 2017-00644SIMPLER
Available from: 2023-09-27 Created: 2023-09-27 Last updated: 2025-02-11Bibliographically approved
Brasky, T. M., Hade, E. M., Cohn, D. E., Newton, A. M., Petruzella, S., O'Connell, K., . . . Neuhouser, M. L. (2023). Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis. Gynecologic Oncology, 169, 137-146
Open this publication in new window or tab >>Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis
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2023 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 169, p. 137-146Article in journal (Refereed) Published
Abstract [en]

Background. Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial can-cer risk; particularly among certain subgroups characterized by body mass and tumor pathology.

Materials and methods. Data from 12 prospective cohort studies participating in the Epidemiology of Endome-trial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid in-takes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study -specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk.

Results. Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were as-sociated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not dif-fer by cancer grade.

Conclusion. Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly over-weight/obese women.(c) 2022 Elsevier Inc. All rights reserved.
Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Endometrial cancer, Fatty acid, Omega-3, Polyunsaturated, Uterine cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-500028 (URN)10.1016/j.ygyno.2022.10.015 (DOI)000944496500001 ()36934308 (PubMedID)
Funder
Swedish Research Council
Available from: 2023-04-11 Created: 2023-04-11 Last updated: 2023-04-11Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7387-6845

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