Alcohol intake and endogenous sex hormones in women: Meta‐analysis of cohort studies and Mendelian randomization

Author:

Tin Tin Sandar1ORCID,Smith‐Byrne Karl1,Ferrari Pietro2,Rinaldi Sabina2,McCullough Marjorie L.3,Teras Lauren R.3,Manjer Jonas4,Giles Graham5,Le Marchand Loïc6,Haiman Christopher A.7,Wilkens Lynne R.6,Chen Yu8,Hankinson Sue9,Tworoger Shelley10,Eliassen A. Heather1112,Willett Walter C.1112,Ziegler Regina G.13,Fuhrman Barbara J.14,Sieri Sabina15,Agnoli Claudia15,Cauley Jane16,Menon Usha17,Fourkala Evangelia Ourania18,Rohan Thomas E.19,Kaaks Rudolf20,Reeves Gillian K.1,Key Timothy J.1

Affiliation:

1. Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford Oxford UK

2. International Agency for Research on Cancer (IARC/WHO) Nutrition and Metabolism Branch Lyon France

3. Department of Population Science American Cancer Society Atlanta Georgia USA

4. Department of Surgery Skåne University Hospital Malmö Lund University Malmö Sweden

5. Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia

6. University of Hawai‘i Cancer Center University of Hawai‘i Honolulu Hawaii USA

7. USC Norris Comprehensive Cancer Center University of Southern California Los Angeles California USA

8. Division of Epidemiology Department of Population Health New York University Grossman School of Medicine New York New York USA

9. Department of Biostatistics and Epidemiology School of Public Health and Health Sciences University of Massachusetts Amherst Massachusetts USA

10. Knight Cancer Institute Oregon Health & Science University Portland Oregon USA

11. Departments of Nutrition & Epidemiology Harvard T.H. Chan School of Public Health Boston Massachusetts USA

12. Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital Boston Massachusetts USA

13. Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland USA

14. Pediatrics University of Pittsburgh Pittsburgh Pennsylvania USA

15. Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

16. Department of Epidemiology Graduate School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA

17. MRC Clinical Trials Unit Institute of Clinical Trials and Methodology University College London London UK

18. EGA Institute for Women's Health University College London London UK

19. Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx New York USA

20. Division of Cancer Epidemiology German Cancer Research Center, DKFZ Heidelberg Germany

Abstract

AbstractBackgroundThe mechanisms underlying alcohol‐induced breast carcinogenesis are not fully understood but may involve hormonal changes.MethodsCross‐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).ResultsAlcohol 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).ConclusionsAlcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.

Funder

Cancer Research UK

Health Research Council of New Zealand

Publisher

Wiley

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