Evaluating the role of alcohol consumption in breast and ovarian cancer susceptibility using population-based cohort studies and two-sample Mendelian randomization analyses
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Alcohol consumption is correlated positively with risk for breast cancer in observational studies, but observational studies are subject to reverse causation and confounding. The association with epithelial ovarian cancer (EOC) is unclear. We performed both observational Cox regression and two-sample Mendelian randomization (MR) analyses using data from various European cohort studies (observational) and publicly available cancer consortia (MR). These estimates were compared to World Cancer Research Fund (WCRF) findings. In our observational analyses, the multivariable-adjusted hazard ratios (HR) for a one standard drink/day increase was 1.06 (95% confidence interval [CI]; 1.04, 1.08) for breast cancer and 1.00 (0.92, 1.08) for EOC, both of which were consistent with previous WCRF findings. MR ORs per genetically predicted one standard drink/day increase estimated via 34 SNPs using MR-PRESSO were 1.00 (0.93, 1.08) for breast cancer and 0.95 (0.85, 1.06) for EOC. Stratification by EOC subtype or estrogen receptor status in breast cancers made no meaningful difference to the results. For breast cancer, the CIs for the genetically derived estimates include the point-estimate from observational studies so are not inconsistent with a small increase in risk. Our data provide additional evidence that alcohol intake is unlikely to have anything other than a very small effect on risk of EOC.
| Original language | English |
|---|---|
| Journal | International Journal of Cancer |
| Volume | 148 |
| Issue number | 6 |
| Pages (from-to) | 1338-1350 |
| ISSN | 0020-7136 |
| DOIs | |
| Publication status | Published - 2021 |
Bibliographical note
Funding Information:
We would like to thank the staff and participants of the CCHS, CGPS, KARMA and UK Biobank cohort study. We thank Scott Wood and John Pearson from QIMR Berghofer for IT support. The breast cancer genome‐wide association analyses were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the “Ministère de l'Économie, de la Science et de l'Innovation du Québec” through Genome Québec and grant PSR‐SIIRI‐701, the National Institutes of Health (U19 CA148065, X01HG007492), Cancer Research UK (C1287/A10118, C1287/A16563, C1287/A10710) and the European Union (HEALTH‐F2‐2009‐223175 and H2020 633784 and H2020 634935). All studies and funders are listed in Michailidou et al (2017). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund, thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME‐ON Post‐GWAS Initiative (U19‐CA148112). Our study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). Detailed funding and acknowledgements for the BCAC and OCAC studies are provided in the supplementary material.
Funding Information:
This work was conducted using the UK Biobank Resource (application number 25331). This work is supported by a project grant (1123248) from the Australian National Health and Medical Research Council (NHMRC). Stuart MacGregor, Penelope M. Webb and Georgia Chenevix‐Trench are supported by fellowships from the NHMRC. Funding for the CCHS and CGPS were obtained from the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.
Funding Information:
National Health and Medical Research Council, Grant/Award Number: 1123248; UK Biobank Resource, Grant/Award Number: 25331; Cancer Genome Atlas Pilot Project, Grant/Award Number: phs000178.v8.p7; Wellcome Trust Case Control consortium, Grant/Award Number: 076113; US National Cancer Institute GAME‐ON Post‐GWAS Initiative, Grant/Award Number: U19‐CA148112; the European Union, Grant/Award Numbers: H2020 634935, H2020 633784, HEALTH‐F2‐2009‐223175; Cancer Research UK, Grant/Award Numbers: C1287/A10710, C1287/A16563, C1287/A10118; National Institutes of Health, Grant/Award Numbers: X01HG007492, U19 CA148065; Ministère de l'Économie, de la Science et de l'Innovation du Québec, Grant/Award Number: PSR‐SIIRI‐701 Funding information
Funding Information:
We would like to thank the staff and participants of the CCHS, CGPS, KARMA and UK Biobank cohort study. We thank Scott Wood and John Pearson from QIMR Berghofer for IT support. The breast cancer genome-wide association analyses were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ?Minist?re de l'?conomie, de la Science et de l'Innovation du Qu?bec? through Genome Qu?bec and grant PSR-SIIRI-701, the National Institutes of Health (U19 CA148065, X01HG007492), Cancer Research UK (C1287/A10118, C1287/A16563, C1287/A10710) and the European Union (HEALTH-F2-2009-223175 and H2020 633784 and H2020 634935). All studies and funders are listed in Michailidou et al (2017). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund, thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). Our study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). Detailed funding and acknowledgements for the BCAC and OCAC studies are provided in the supplementary material. This work was conducted using the UK Biobank Resource (application number 25331). This work is supported by a project grant (1123248) from the Australian National Health and Medical Research Council (NHMRC). Stuart MacGregor, Penelope M. Webb and Georgia Chenevix-Trench are supported by fellowships from the NHMRC. Funding for the CCHS and CGPS were obtained from the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.
Publisher Copyright:
© 2020 Union for International Cancer Control
- alcohol intake, breast cancer, causal inference, Mendelian randomization, ovarian cancer
Research areas
ID: 302172020