TY - JOUR
T1 - Alcohol consumption and prostate cancer incidence and progression
T2 - A Mendelian randomisation study
AU - The PRACTICAL Consortium
AU - Brunner, Clair
AU - Davies, Neil M.
AU - Martin, Richard M.
AU - Eeles, Rosalind
AU - Easton, Doug
AU - Kote-Jarai, Zsofia
AU - Al Olama, Ali Amin
AU - Benlloch, Sara
AU - Muir, Kenneth
AU - Giles, Graham
AU - Wiklund, Fredrik
AU - Gronberg, Henrik
AU - Haiman, Christopher A.
AU - Schleutker, Johanna
AU - Nordestgaard, Børge G.
AU - Travis, Ruth C.
AU - Neal, David
AU - Donovan, Jenny
AU - Hamdy, Freddie C.
AU - Pashayan, Nora
AU - Khaw, Kay Tee
AU - Stanford, Janet L.
AU - Blot, William J.
AU - Thibodeau, Stephen
AU - Maier, Christiane
AU - Kibel, Adam S.
AU - Cybulski, Cezary
AU - Cannon-Albright, Lisa
AU - Brenner, Hermann
AU - Park, Jong
AU - Kaneva, Radka
AU - Batra, Jyotsna
AU - Teixeira, Manuel R.
AU - Pandha, Hardev
AU - Zuccolo, Luisa
N1 - Publisher Copyright:
© 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Mendelian randomisation
KW - alcohol
KW - alcohol metabolising genes
KW - prostate cancer
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U2 - 10.1002/ijc.30436
DO - 10.1002/ijc.30436
M3 - Article
C2 - 27643404
AN - SCOPUS:84991075562
SN - 0020-7136
VL - 140
SP - 75
EP - 85
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -