Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium.
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
- The Institute of Cancer Research, 15 Cotswold Road, Sutton, London SM2 5NG, UK.
- Strangeways Research Laboratory, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, 2 Worts' Causeway, Cambridge CB1 8RN, UK.
- Institute of Population Health, University of Warwick, Coventry CV4 7AL, UK.
- Cancer Epidemiology Centre, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.
- Department of Medical Biochemistry and Genetics, University of Turku, Turku 20014, Finland.
- Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev 2730, Denmark.
- Cancer Epidemiology, Nuffield Department of Population Health University of Oxford, Oxford OX3 7LF, UK.
- School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
- Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
- International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD 20850, USA.
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
- Institute of Human Genetics, University Hospital Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
- Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA 02115, USA.
- Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Rybacka 1, Szczecin, Poland.
- Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.
- Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Research Center, Heidelberg 69120, Germany.
- Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
- Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
- Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation and Schools of Life Science and Public Health, Queensland University of Technology, Brisbane, Queensland 4102, Australia.
- Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
- Department of Clinical and Experimental Medicine, Targeted Cancer Therapy, The University of Surrey, Guildford, Surrey GU2 7XH, UK.
BACKGROUND: Prostate cancer is a common cancer worldwide with no established modifiable lifestyle factors to guide prevention. The associations between polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been inconsistent. Using Mendelian randomisation, we evaluated associations between PUFAs and prostate cancer risk.
METHODS: We used individual-level data from a consortium of 22 721 cases and 23 034 controls of European ancestry. Externally-weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation ranging from 0.65 to 33.07%, were constructed and used to evaluate associations with prostate cancer risk per one standard deviation (s.d.) increase in genetically-predicted plasma PUFA levels using multivariable-adjusted unconditional logistic regression.
RESULTS: No overall association was observed between the genetically-predicted PUFAs evaluated in this study and prostate cancer risk. However, risk reductions were observed for short-chain PUFAs, linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and α-linolenic acids (ORALA=0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ⩾62 years for LA (ORLA=1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e., arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were observed among men <62 years (ORAA=1.05, 95%CI=1.02, 1.08; OREPA=1.04, 95%CI=1.01, 1.06; ORDPA=1.05, 95%CI=1.02, 1.08).
CONCLUSION: Results from this study suggest that circulating ω-3 and ω-6 PUFAs may have a different role in the aetiology of early- and late-onset prostate cancer.