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

Clair Brunner, Neil M Davies, Richard Martin, Rosalind Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Fredrik Wiklund, Henrik Grönberg, Christopher A Haiman, Johanna Schleutker, Børge G Nordestgaard, Ruth C Travis, David E. Neal, Jenny Donovan, Nora Pashayan, Kay-Tee KhawJanet L Stanford, William J Blot, Stephen Thibodeau, Christiane Maier, Adam S Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Park, Radka Kaneva, Jyotsna Batra, Manuel R Teixeira, Hardev Pandha, the PRACTICAL Consortium, Luisa Zuccolo

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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 the current 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 metaanalyses. 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-value=0.002); rs12910509, HRfixed=0.76; 95%CI:0.64,0.91; pvalue=0.003); and rs8041922 (HRfixed=0.76; 95%CI:0.64,0.91; p-value=0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed=1.43; 95%CI:1.14,1.79; p-value=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.
Original languageEnglish
Pages (from-to)75-85
Number of pages11
JournalInternational Journal of Cancer
Volume140
Issue number1
Early online date8 Oct 2016
DOIs
Publication statusPublished - 1 Jan 2017

Structured keywords

  • ICEP
  • Centre for Surgical Research

Keywords

  • alcohol;
  • prostate cancer
  • alcohol metabolising genes
  • Mendelian randomization

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    MRC UoB UNITE Unit - Programme 1

    Davey Smith, G.

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    Windmeijer, F., Tilling, K. M. & Tilling, K. M.

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    Cite this

    Brunner, C., Davies, N. M., Martin, R., Eeles, R., Easton, D., Kote-Jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Grönberg, H., Haiman, C. A., Schleutker, J., Nordestgaard, B. G., Travis, R. C., Neal, D. E., Donovan, J., Pashayan, N., ... Zuccolo, L. (2017). Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study. International Journal of Cancer, 140(1), 75-85. https://doi.org/10.1002/ijc.30436