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 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.
authors.affiliation: 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.
authors.forename: Clair
authors.initials: C
authors.lastname: Brunner
authors.affiliation: 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.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Davies
authors.affiliation: 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.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: The Institute of Cancer Research, London, SM2 5NG, United Kingdom.|Royal Marsden NHS Foundation Trust, London, SW3 6JJ, United Kingdom.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.affiliation: Strangeways Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Worts Causeway, Cambridge, United Kingdom.
authors.forename: Doug
authors.initials: D
authors.lastname: Easton
authors.affiliation: The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.affiliation: Strangeways Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Worts Causeway, Cambridge, United Kingdom.
authors.forename: Ali Amin
authors.initials: AA
authors.lastname: Al Olama
authors.affiliation: Strangeways Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Worts Causeway, Cambridge, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Benlloch
authors.affiliation: Institute of Population Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.affiliation: 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.
authors.forename: Graham
authors.initials: G
authors.lastname: Giles
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gronberg
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.|Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Neal
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.affiliation: Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: 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.
authors.forename: Nora
authors.initials: N
authors.lastname: Pashayan
authors.affiliation: Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.|Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.affiliation: International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, MD.
authors.forename: William J
authors.initials: WJ
authors.lastname: Blot
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Stephen
authors.initials: S
authors.lastname: Thibodeau
authors.affiliation: Department of Urology, University Hospital Ulm, Germany.|Institute of Human Genetics University Hospital Ulm, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Maier
authors.affiliation: Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA.|Washington University, St Louis, MO.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kibel
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.affiliation: Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cannon-Albright
authors.affiliation: 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.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, FL.
authors.forename: Jong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University Sofia, 2 Zdrave St, Sofia, 1431, Bulgaria.
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.affiliation: 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.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Batra
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal and Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.affiliation: The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
authors.affiliation: 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.
authors.forename: Luisa
authors.initials: L
authors.lastname: Zuccolo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology*; D012044:Regression Analysis; D050697:Retinal Dehydrogenase / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; C524846:ALDH1B1 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase
keywords: Mendelian randomisation; alcohol; alcohol metabolising genes; prostate cancer