Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study.
Clair Brunner, Neil M Davies, Richard M Martin, Rosalind Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A Haiman, Johanna Schleutker, Børge G Nordestgaard, Ruth C Travis, David Neal, Jenny Donovan, Freddie C Hamdy, 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, Luisa Zuccolo
Journal: International journal of cancer
2017;140(1):75-85
PMID: 27643404
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, HR = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HR = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HR = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HR = 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.
© 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Address:
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.; MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.; MRC/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; The NIHR Bristol Nutrition Biomedical Research Unit, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom.; The Institute of Cancer Research, London, SM2 5NG, United Kingdom.; Royal Marsden NHS Foundation Trust, London, SW3 6JJ, United Kingdom.; Strangeways Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Worts Causeway, Cambridge, United Kingdom.; The Institute of Cancer Research, London, SM2 5NG, United Kingdom.; Institute of Population Health, University of Manchester, Manchester, United Kingdom.; The Cancer Council Victoria, Cancer Epidemiology Centre, 1 Rathdowne Street, Carlton, Vic, Australia.; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Vic, Australia.; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.; Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA.; Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.; Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Denmark.; Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.; Surgical Oncology (Uro-Oncology: S4), University of Cambridge, Box 279, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom.; Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.; School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.; Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.; Strangeways Laboratory, Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Worts Causeway, Cambridge, United Kingdom.; Department of Applied Health Research, University College London, 1-19 Torrington Place, London, WC1E 7HB, United Kingdom.; Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom.; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.; International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, MD.; Mayo Clinic, Rochester, MN.; Department of Urology, University Hospital Ulm, Germany.; Institute of Human Genetics University Hospital Ulm, Germany.; Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA.; Washington University, St Louis, MO.; Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.; Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, FL.; Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.; Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and Schools of Life Science and Public Health, Queensland University of Technology, BNE, Australia.; Department of Genetics, Portuguese Oncology Institute, Porto, Portugal and Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.; The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
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MeSH Terms:
Aged,
Aged, 80 and over,
Alcohol Drinking,
Aldehyde Dehydrogenase,
Aldehyde Dehydrogenase 1 Family,
Aldehyde Dehydrogenase, Mitochondrial,
Case-Control Studies,
Disease Progression,
Humans,
Incidence,
Linkage Disequilibrium,
Male,
Middle Aged,
Neoplasm Grading,
Polymorphism, Single Nucleotide,
Prostatic Neoplasms,
Regression Analysis,
Retinal Dehydrogenase,
Survival Analysis