Dataset Information

Alcohol intake and endogenous sex hormones in women: meta-analysis of cohort studies and Mendelian randomization.

ABSTRACT:

Background

The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.

Methods

We investigated cross-sectional associations between self-reported alcohol intake and serum or plasma concentrations of oestradiol, oestrone, progesterone (in pre-menopausal women only), testosterone, androstenedione, DHEAS (dehydroepiandrosterone sulphate) and SHBG (sex hormone binding globulin) in 45 431 pre-menopausal and 173 476 post-menopausal women. We performed multivariable linear regression separately for UK Biobank, EPIC (European Prospective Investigation into Cancer and Nutrition) and EHBCCG (Endogenous Hormones and Breast Cancer Collaborative Group), and meta-analysed the results. For testosterone and SHBG, we also conducted two-sample Mendelian Randomization (MR) and colocalisation using the ADH1B (Alcohol Dehydrogenase 1B) variant (rs1229984).

Results

Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in pre-menopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal oestradiol to 6.6% for post-menopausal DHEAS. There was an inverse association of alcohol with SHBG in post-menopausal women but a small positive association in pre-menopausal women. MR 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%, -4.9%). Colocalisation suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (PP4: 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.

SUBMITTER: Tin ST

PROVIDER: S-EPMC10462228 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Alcohol intake and endogenous sex hormones in women: meta-analysis of cohort studies and Mendelian randomization.

Tin Sandar Tin ST Smith-Byrne Karl K Ferrari Pietro P Rinaldi Sabina S McCullough Marjorie L ML Teras Lauren R LR Manjer Jonas J Giles Graham G Marchand Loïc Le LL Haiman Christopher A CA Wilkens Lynne R LR Chen Yu Y Hankinson Sue S Tworoger Shelley S Eliassen A Heather AH Willett Walter C WC Ziegler Regina G RG Fuhrman Barbara J BJ Sieri Sabina S Agnoli Claudia C Cauley Jane J Menon Usha U Fourkala Evangelia Ounia EO Rohan Thomas E TE Kaaks Rudolf R Reeves Gillian K GK Key Timothy J TJ

Research square 20230816

<h4>Background</h4>The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes.<h4>Methods</h4>We investigated cross-sectional associations between self-reported alcohol intake and serum or plasma concentrations of oestradiol, oestrone, progesterone (in pre-menopausal women only), testosterone, androstenedione, DHEAS (dehydroepiandrosterone sulphate) and SHBG (sex hormone binding globulin) in 45 431 pre-menopausal and 173 476 post-men ...[more]

PMID: 37645769

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Project description:BackgroundThe risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased in postmenopausal women compared with men of similar age, suggesting a role for sex hormones. We aimed to explore whether sex hormones, and age at menarche/menopause have a causal effect on aSAH risk by conducting a 2-sample MR study (Mendelian randomization).MethodsWe obtained sex-specific genetic instruments for serum estradiol, bioavailable testosterone (BioT), SHBG (sex hormone-binding globulin), and age at menarche/menopause from genome-wide association studies. The associated sex-specific aSAH risk was estimated with inverse-variance weighted MR analyses with various statistical sensitivity analyses. Multivariable and cluster MR analyses were performed for BioT and SHBG to account for a genetic and phenotypic correlation between the 2 exposures. The clusters represented (1) single-nucleotide polymorphisms primarily increasing SHBG, with secondary decreasing effects on BioT, and (2) single-nucleotide polymorphisms affecting BioT without affecting SHBG.ResultsUnivariable MR analyses showed an 18% increased aSAH risk among women per 1-SD increase in genetically determined SHBG levels (odds ratio, 1.18 [95% CI, 1.05-1.34]; P=0.007). Suggestive evidence was identified for a 27% decreased risk of aSAH among women per 1-SD increase in BioT (odds ratio, 0.73 [95% CI, 0.55-0.95]; P=0.02). The latter association disappeared in cluster analysis when only using SHBG-independent variants. MR analyses with variants from the cluster with primary SHBG effects and secondary (opposite) BioT-effects yielded a statistically significant association (odds ratio, 1.21 [95% CI, 1.05-1.40]; P=0.008). No other causal associations were identified.ConclusionsGenetic predisposition to elevated serum levels of SHBG, with secondary lower serum BioT levels, is associated with an increased aSAH risk among women, suggesting that SHBG and BioT causally elevate aSAH risk. Further studies are required to elucidate the underlying mechanisms and their potential as an interventional target to lower aSAH incidence.

Dataset Information

Alcohol intake and endogenous sex hormones in women: meta-analysis of cohort studies and Mendelian randomization.

Background

Methods

Results

Conclusions

Publications

Alcohol intake and endogenous sex hormones in women: meta-analysis of cohort studies and Mendelian randomization.

Similar Datasets

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