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

Nikhil K. Khankari, Harvey J. Murff, Chenjie Zeng, Wanqing Wen, Rosalind A. Eeles, Douglas F. Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A. Haiman, Johanna Schleutker, BØrge G. Nordestgaard, Ruth C. Travis, Jenny L. Donovan, Nora Pashayan, Kay Tee KhawJanet L. Stanford, William J. Blot, Stephen N. Thibodeau, Christiane Maier, Adam S. Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Park, Radka Kaneva, Jyotsna Batra, Manuel R. Teixeira, Hardev Pandha, Wei Zheng

Research output: Contribution to journalArticle

13 Scopus citations

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 (OR LA =0.95, 95%CI=0.92, 0.98) and α-linolenic acids (OR ALA =0.96, 95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among men ≥62 years for LA (OR LA =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 (OR AA =1.05, 95%CI=1.02, 1.08; OR EPA =1.04, 95%CI=1.01, 1.06; OR DPA =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.

Original languageEnglish (US)
Pages (from-to)624-631
Number of pages8
JournalBritish journal of cancer
Volume115
Issue number5
DOIs
StatePublished - Aug 23 2016

Keywords

  • polyunsaturated fatty acids; prostate cancer; Mendelian randomisation; polygenic risk score; omega-3 fatty acids; omega-6 fatty acids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Polyunsaturated fatty acids and prostate cancer risk: A Mendelian randomisation analysis from the PRACTICAL consortium'. Together they form a unique fingerprint.

  • Cite this

    Khankari, N. K., Murff, H. J., Zeng, C., Wen, W., Eeles, R. A., Easton, D. F., Kote-Jarai, Z., Al Olama, A. A., Benlloch, S., Muir, K., Giles, G. G., Wiklund, F., Gronberg, H., Haiman, C. A., Schleutker, J., Nordestgaard, BØ. G., Travis, R. C., Donovan, J. L., Pashayan, N., ... Zheng, W. (2016). Polyunsaturated fatty acids and prostate cancer risk: A Mendelian randomisation analysis from the PRACTICAL consortium. British journal of cancer, 115(5), 624-631. https://doi.org/10.1038/bjc.2016.228