Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

doi:10.1038/bjc.2016.228

. 2016 Aug 23;115(5):624-31.

doi: 10.1038/bjc.2016.228. Epub 2016 Aug 4.

Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

Nikhil K Khankari¹, Harvey J Murff¹, Chenjie Zeng¹, Wanqing Wen¹, Rosalind A Eeles^{2

3}, Douglas F Easton⁴, Zsofia Kote-Jarai², Ali Amin Al Olama⁴, Sara Benlloch⁴, Kenneth Muir⁵, Graham G Giles^{6

7}, Fredrik Wiklund⁸, Henrik Gronberg⁸, Christopher A Haiman⁹, Johanna Schleutker^{10

11}, Børge G Nordestgaard¹², Ruth C Travis¹³, Jenny L Donovan¹⁴, Nora Pashayan^{4

15}, Kay-Tee Khaw¹⁶, Janet L Stanford^{17

18}, William J Blot¹⁹, Stephen N Thibodeau²⁰, Christiane Maier^{21

22}, Adam S Kibel^{23

24}, Cezary Cybulski²⁵, Lisa Cannon-Albright²⁶, Hermann Brenner^{27

28}, Jong Park²⁹, Radka Kaneva³⁰, Jyotsna Batra³¹, Manuel R Teixeira^{32

33}, Hardev Pandha³⁴, Wei Zheng¹; PRACTICAL consortium

Affiliations

¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
² The Institute of Cancer Research, 15 Cotswold Road, Sutton, London SM2 5NG, UK.
³ Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
⁴ 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.
⁵ Institute of Population Health, University of Warwick, Coventry CV4 7AL, UK.
⁶ Cancer Epidemiology Centre, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia.
⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
⁸ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.
¹⁰ Department of Medical Biochemistry and Genetics, University of Turku, Turku 20014, Finland.
¹¹ Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Kalevantie 4, Tampere 33014, Finland.
¹² Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev 2730, Denmark.
¹³ Cancer Epidemiology, Nuffield Department of Population Health University of Oxford, Oxford OX3 7LF, UK.
¹⁴ School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
¹⁵ Department of Applied Health Research, University College London, 1-19 Torrington Place, London WC1E 7HB, UK.
¹⁶ Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.
¹⁷ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
¹⁸ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA.
¹⁹ International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD 20850, USA.
²⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
²¹ Institute of Human Genetics, University Hospital Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
²² Department of Urology, University Hospital Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
²³ Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA 02115, USA.
²⁴ Washington University, 660 S. Euclid Avenue, St Louis, MO 63110, USA.
²⁵ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Rybacka 1, Szczecin, Poland.
²⁶ Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.
²⁷ Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Research Center, Heidelberg 69120, Germany.
²⁸ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
²⁹ Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
³⁰ Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
³¹ 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.
³² Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
³³ Biomedical Sciences Institute (ICBAS), Porto University, 4200-072 Porto, Portugal.
³⁴ Department of Clinical and Experimental Medicine, Targeted Cancer Therapy, The University of Surrey, Guildford, Surrey GU2 7XH, UK.

PMID: 27490808
PMCID: PMC4997551
DOI: 10.1038/bjc.2016.228

Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

Nikhil K Khankari et al. Br J Cancer. 2016.

. 2016 Aug 23;115(5):624-31.

doi: 10.1038/bjc.2016.228. Epub 2016 Aug 4.

Authors

Affiliations

¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
² The Institute of Cancer Research, 15 Cotswold Road, Sutton, London SM2 5NG, UK.
³ Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
⁴ 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.
⁵ Institute of Population Health, University of Warwick, Coventry CV4 7AL, UK.
⁶ Cancer Epidemiology Centre, Cancer Council Victoria, 615 St Kilda Road, Melbourne, Victoria 3004, Australia.
⁷ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
⁸ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 171 77, Sweden.
⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089, USA.
¹⁰ Department of Medical Biochemistry and Genetics, University of Turku, Turku 20014, Finland.
¹¹ Institute of Biomedical Technology/BioMediTech, University of Tampere and FimLab Laboratories, Kalevantie 4, Tampere 33014, Finland.
¹² Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, Herlev 2730, Denmark.
¹³ Cancer Epidemiology, Nuffield Department of Population Health University of Oxford, Oxford OX3 7LF, UK.
¹⁴ School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, UK.
¹⁵ Department of Applied Health Research, University College London, 1-19 Torrington Place, London WC1E 7HB, UK.
¹⁶ Cambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.
¹⁷ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
¹⁸ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA.
¹⁹ International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD 20850, USA.
²⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
²¹ Institute of Human Genetics, University Hospital Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
²² Department of Urology, University Hospital Ulm, Albert-Einstein-Allee 11, Ulm 89081, Germany.
²³ Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA 02115, USA.
²⁴ Washington University, 660 S. Euclid Avenue, St Louis, MO 63110, USA.
²⁵ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Rybacka 1, Szczecin, Poland.
²⁶ Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.
²⁷ Division of Clinical Epidemiology and Aging Research, Division of Preventive Oncology, German Cancer Research Center, Heidelberg 69120, Germany.
²⁸ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
²⁹ Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
³⁰ Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 2 Zdrave Street, 1431 Sofia, Bulgaria.
³¹ 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.
³² Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
³³ Biomedical Sciences Institute (ICBAS), Porto University, 4200-072 Porto, Portugal.
³⁴ Department of Clinical and Experimental Medicine, Targeted Cancer Therapy, The University of Surrey, Guildford, Surrey GU2 7XH, UK.

PMID: 27490808
PMCID: PMC4997551
DOI: 10.1038/bjc.2016.228

Abstract

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.

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References

1. Ahmad OS, Morris JA, Mujammami M, Forgetta V, Leong A, Li R, Turgeon M, Greenwood CMT, Thanassoulis G, Meigs JB, Sladek R, Richards JB (2015) A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease. Nat Commun 6: 7060. - PMC - PubMed
1. Alexander DD, Bassett JK, Weed DL, Barrett EC, Watson H, Harris W (2015) Meta-analysis of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) and prostate cancer. Nutr Cancer 67: 543–554. - PMC - PubMed
1. Arab L (2003) Biomarkers of fat and fatty acid intake. J Nutr 133 (Suppl 3): 925S–932S. - PubMed
1. Berquin IM, Edwards IJ, Kridel SJ, Chen YQ (2011) Polyunsaturated fatty acid metabolism in prostate cancer. Cancer Metastasis Rev 30: 295–309. - PMC - PubMed
1. Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44: 512–525. - PMC - PubMed

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[1] Ahmad OS, Morris JA, Mujammami M, Forgetta V, Leong A, Li R, Turgeon M, Greenwood CMT, Thanassoulis G, Meigs JB, Sladek R, Richards JB (2015) A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease. Nat Commun 6: 7060. - PMC - PubMed

[2] Ahmad OS, Morris JA, Mujammami M, Forgetta V, Leong A, Li R, Turgeon M, Greenwood CMT, Thanassoulis G, Meigs JB, Sladek R, Richards JB (2015) A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease. Nat Commun 6: 7060. - PMC - PubMed

[3] Alexander DD, Bassett JK, Weed DL, Barrett EC, Watson H, Harris W (2015) Meta-analysis of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) and prostate cancer. Nutr Cancer 67: 543–554. - PMC - PubMed

[4] Alexander DD, Bassett JK, Weed DL, Barrett EC, Watson H, Harris W (2015) Meta-analysis of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) and prostate cancer. Nutr Cancer 67: 543–554. - PMC - PubMed

[5] Arab L (2003) Biomarkers of fat and fatty acid intake. J Nutr 133 (Suppl 3): 925S–932S. - PubMed

[6] Arab L (2003) Biomarkers of fat and fatty acid intake. J Nutr 133 (Suppl 3): 925S–932S. - PubMed

[7] Berquin IM, Edwards IJ, Kridel SJ, Chen YQ (2011) Polyunsaturated fatty acid metabolism in prostate cancer. Cancer Metastasis Rev 30: 295–309. - PMC - PubMed

[8] Berquin IM, Edwards IJ, Kridel SJ, Chen YQ (2011) Polyunsaturated fatty acid metabolism in prostate cancer. Cancer Metastasis Rev 30: 295–309. - PMC - PubMed

[9] Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44: 512–525. - PMC - PubMed

[10] Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44: 512–525. - PMC - PubMed

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Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

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Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation analysis from the PRACTICAL consortium

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