Alcohol intake and endogenous sex hormones in women: Meta‐analysis of cohort studies and Mendelian randomization
Year: 2024
Type: review
Abstract: BACKGROUND: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. METHODS: Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984). RESULTS: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively). CONCLUSIONS: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.
Source: Cancer
DOI: 10.1002/cncr.35391
Authors: Sandar Tin Tin, Karl Smith‐Byrne, Pietro Ferrari, Sabina Rinaldi, Marjorie L. McCullough, Lauren R. Teras, Jonas Manjer, Graham Giles, Loïc Le Marchand, Christopher A. Haiman, Lynne R. Wilkens, Yu Chen, Sue Hankinson, Shelley Tworoger, A. Heather Eliassen, Walter C. Willett, Regina G. Ziegler, Barbara J. Fuhrman, Sabina Sieri, Claudia Agnoli, Jane Cauley, Usha Menon, Evangelia Ourania Fourkala, Thomas E. Rohan, Rudolf Kaaks, Gillian K. Reeves, Timothy J. Key
Institutions: University of Oxford, Centre international de recherche sur le cancer, American Cancer Society, Lund University, Skåne University Hospital, Cancer Council Victoria, University of Hawaii Cancer Center, University of Southern California, USC Norris Comprehensive Cancer Center, New York University, University of Massachusetts Amherst, Oregon Health & Science University, OHSU Knight Cancer Institute, Brigham and Women's Hospital, Harvard University, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University of Pittsburgh, Fondazione IRCCS Istituto Nazionale dei Tumori, MRC Clinical Trials Unit at UCL, University College London, Albert Einstein College of Medicine, German Cancer Research Center
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,740
Awards: G1169685992, G151562090, G1788645866, G2149865848, G2344417776, G2419028985, Biochemical Markers in the nurses' Health Study Cohort, G2663613759, G3328679326, G3602225402, G361298724, Million Women Study, G4287663350, G4306957257, G4376790518, G4409899835, G4412304022, G4844208673, G4926209728, G4964662507, G5058239881, G5724888378, G6079465987, G6200764915, G6868151656, G737619643, G7483307776, Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health Study, G7610968641, G7998126057, G8079377165, Premenopausal Hormone Levels and Risk of Breast Cancer, G8658876294, G8871309901, Evaluating new healthcare technologies in cancer, G9000019617, G9000028950, G9000058679, G9000084571, G9000185549, Life Course Cancer Epidemiology Cohort in Women, University of Hawaii Cancer Center CCSG, Understanding Population Differences in Cancer: The MEC Study
OpenAlex ID: W4399275695