title: Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis.
abstract: Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all-cause and prostate cancer-specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated with prostate cancer risk (OR per additional coffee increasing allele: 1.01, 95% CI: 0.98,1.03) or having high-grade compared to low-grade disease (OR: 1.01, 95% CI: 0.97,1.04). There was some evidence that the genetic risk score was associated with higher odds of having nonlocalised compared to localised stage disease (OR: 1.03, 95% CI: 1.01, 1.06). Amongst men with prostate cancer, there was no clear association between the genetic risk score and all-cause mortality (HR: 1.00, 95% CI: 0.97,1.04) or prostate cancer-specific mortality (HR: 1.03, 95% CI: 0.98,1.08). These results, which should have less bias from confounding than observational estimates, are not consistent with a substantial effect of coffee consumption on reducing prostate cancer incidence or progression.
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, United Kingdom.|School of Experimental Psychology and UK Centre for Tobacco and Alcohol Studies, University of Bristol, Bristol, United Kingdom.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Taylor
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, United Kingdom.|School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.|The NIHR Bristol Nutrition Biomedical Research Unit, University Hospitals Bristol NHS Foundation Trust and the University of Bristol.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Milan S
authors.initials: MS
authors.lastname: Geybels
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: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Irene
authors.initials: I
authors.lastname: Shui
authors.affiliation: The Institute of Cancer Research, London, SM2 5NG, United Kingdom.|The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, United Kingdom.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.affiliation: Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, 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, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, United Kingdom.
authors.forename: Ali
authors.initials: A
authors.lastname: Amin Al Olama
authors.affiliation: Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, 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: Cancer Epidemiology Centre, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Graham G
authors.initials: GG
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, Herlev, 2730, 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, Addenbrooke's Hospital, Hills Road, Box 279, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Neal
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.|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: International Epidemiology Institute, 1455 Research Blvd, Suite 550, Rockville, MD.
authors.forename: William
authors.initials: W
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, Ulm, Germany.|Institute of Human Genetics, University Hospital Ulm, 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, School of Medicine, St. Louis, MO.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kibel
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, 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: Molecular Medicine Center and Department of Medical Chemistry and Biochemistry, 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 School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Batra
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.|Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.affiliation: Faculty of Health & Medical Sciences, 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.
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.affiliation: MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, Bristol, United Kingdom.|School of Experimental Psychology and UK Centre for Tobacco and Alcohol Studies, University of Bristol, Bristol, United Kingdom.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Munafò
mesh_terms: D000368:Aged; D000483:Alleles; D003069:Coffee / Q000009:adverse effects*; D018450:Disease Progression; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis / Q000379:methods; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D012307:Risk Factors
chemical_list: D003069:Coffee
keywords: Mendelian randomization; coffee; prostate cancer