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 Khaw; Janet 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

doi:10.1002/ijc.30436

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, HR_fixed=0.78; 95% confidence interval (95%CI):0.66,0.91; p-value=0.002); rs12910509, HR_fixed=0.76; 95%CI:0.64,0.91; pvalue=0.003); and rs8041922 (HR_fixed=0.76; 95%CI:0.64,0.91; p-value=0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HR_fixed=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 language	English
Pages (from-to)	75-85
Number of pages	11
Journal	International Journal of Cancer
Volume	140
Issue number	1
Early online date	8 Oct 2016
DOIs	https://doi.org/10.1002/ijc.30436
Publication status	Published - 1 Jan 2017

Structured keywords

ICEP
Centre for Surgical Research

Keywords

alcohol;
prostate cancer
alcohol metabolising genes
Mendelian randomization

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3 Finished

IEU Theme 3
Windmeijer, F., Tilling, K. M. & Tilling, K. M.
1/06/13 → 31/03/18
Project: Research
MRC UoB UNITE Unit - Programme 1
Davey Smith, G.
1/06/13 → 31/03/18
Project: Research
IDENTIFYING POTENTIALLY MODIFIABLE LIFE-STYLE RELATED CAUSES OF CANCER
Zuccolo, L.
1/09/06 → 1/09/10
Project: Research

Dr Luisa Zuccolo
- L.Zuccolo@bristol.ac.uk
- Bristol Medical School (PHS) - Senior Lecturer
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Cancer
Person: Academic , Member

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

Brunner, Clair ; Davies, Neil M ; Martin, Richard ; Eeles, Rosalind ; Easton, Doug ; Kote-Jarai, Zsofia ; Al Olama, Ali Amin ; Benlloch, Sara ; Muir, Kenneth ; Giles, Graham G. ; Wiklund, Fredrik ; Grönberg, Henrik ; Haiman, Christopher A ; Schleutker, Johanna ; Nordestgaard, Børge G ; Travis, Ruth C ; Neal, David E. ; Donovan, Jenny ; Pashayan, Nora ; Khaw, Kay-Tee ; Stanford, Janet L ; Blot, William J ; Thibodeau, Stephen ; Maier, Christiane ; Kibel, Adam S ; Cybulski, Cezary ; Cannon-Albright, Lisa ; Brenner, Hermann ; Park, Jong ; Kaneva, Radka ; Batra, Jyotsna ; Teixeira, Manuel R ; Pandha, Hardev ; the PRACTICAL Consortium ; Zuccolo, Luisa. / Alcohol consumption and prostate cancer incidence and progression : A Mendelian randomisation study. In: International Journal of Cancer. 2017 ; Vol. 140, No. 1. pp. 75-85.

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title = "Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study",

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. ",

keywords = "alcohol;, prostate cancer, alcohol metabolising genes, Mendelian randomization",

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

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month = jan,

day = "1",

doi = "10.1002/ijc.30436",

language = "English",

volume = "140",

pages = "75--85",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "Wiley",

number = "1",

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Brunner, C, Davies, NM , Martin, R, Eeles, R, Easton, D, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Grönberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Neal, DE, Donovan, J, Pashayan, N, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, H, the PRACTICAL Consortium & Zuccolo, L 2017, 'Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study', International Journal of Cancer, vol. 140, no. 1, pp. 75-85. https://doi.org/10.1002/ijc.30436

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

In: International Journal of Cancer, Vol. 140, No. 1, 01.01.2017, p. 75-85.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Alcohol consumption and prostate cancer incidence and progression

T2 - A Mendelian randomisation study

AU - Brunner, Clair

AU - Davies, Neil M

AU - Martin, Richard

AU - Eeles, Rosalind

AU - Easton, Doug

AU - Kote-Jarai, Zsofia

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Giles, Graham G.

AU - Wiklund, Fredrik

AU - Grönberg, Henrik

AU - Haiman, Christopher A

AU - Schleutker, Johanna

AU - Nordestgaard, Børge G

AU - Travis, Ruth C

AU - Neal, David E.

AU - Donovan, Jenny

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 - the PRACTICAL Consortium

AU - Zuccolo, Luisa

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 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.

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 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.

KW - alcohol;

KW - prostate cancer

KW - alcohol metabolising genes

KW - Mendelian randomization

U2 - 10.1002/ijc.30436

DO - 10.1002/ijc.30436

M3 - Article (Academic Journal)

C2 - 27643404

VL - 140

SP - 75

EP - 85

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 1

ER -

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

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Projects

IEU Theme 3

MRC UoB UNITE Unit - Programme 1

IDENTIFYING POTENTIALLY MODIFIABLE LIFE-STYLE RELATED CAUSES OF CANCER

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Dr Luisa Zuccolo

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