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Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

Citation

Brunner, C and Davies, NM and Martin, RM and Eeles, R and Easton, D and Kote-Jarai, Z and Al Olama, AA and Benlloch, S and Muir, K and Giles, G and Wiklund, F and Gronberg, H and Haiman, CA and Schleutker, J and Nordestgaard, BG and Travis, RC and Neal, D and Donovan, J and Hamdy, FC and Pashayan, N and Khaw, KT and Stanford, JL and Blot, WJ and Thibodeau, S and Maier, C and Kibel, AS and Cybulski, C and Cannon-Albright, L and Brenner, H and Park, J and Kaneva, R and Batra, J and Teixeira, MR and Pandha, H and Zuccolo, L and Fitzgerald, LM and The PRACTICAL Consortium, Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study, International Journal of Cancer, 140, (1) pp. 75-85. ISSN 0020-7136 (2016) [Refereed Article]

Copyright Statement

VC 2016 The Authors

DOI: doi:10.1002/ijc.30436

Abstract

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed  = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed  = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.

Item Details

Item Type:Refereed Article
Keywords:prostate cancer mendelian randomisation alcohol
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:114205
Year Published:2016
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-02-08
Last Modified:2017-05-23
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