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

Khankari, NK, Murff, HJ, Zeng, C, Wen, W, Eeles, RA, Easton, DF, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Wiklund, F, Gronberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Donovan, JL, Pashayan, N, Khaw, K, Stanford, JL, Blot, WJ, Thibodeau, SN, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Pandha, HS and Zheng, W (2016) Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomization analysis from the PRACTICAL consortium British Journal of Cancer.

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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 greater than or equal to62 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.

Item Type: Article
Subjects : Medical Science
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
AuthorsEmailORCID
Khankari, NKUNSPECIFIEDUNSPECIFIED
Murff, HJUNSPECIFIEDUNSPECIFIED
Zeng, CUNSPECIFIEDUNSPECIFIED
Wen, WUNSPECIFIEDUNSPECIFIED
Eeles, RAUNSPECIFIEDUNSPECIFIED
Easton, DFUNSPECIFIEDUNSPECIFIED
Kote-Jarai, ZUNSPECIFIEDUNSPECIFIED
Al Olama, AAUNSPECIFIEDUNSPECIFIED
Benlloch, SUNSPECIFIEDUNSPECIFIED
Muir, KUNSPECIFIEDUNSPECIFIED
Giles, GGUNSPECIFIEDUNSPECIFIED
Wiklund, FUNSPECIFIEDUNSPECIFIED
Gronberg, HUNSPECIFIEDUNSPECIFIED
Haiman, CAUNSPECIFIEDUNSPECIFIED
Schleutker, JUNSPECIFIEDUNSPECIFIED
Nordestgaard, BGUNSPECIFIEDUNSPECIFIED
Travis, RCUNSPECIFIEDUNSPECIFIED
Donovan, JLUNSPECIFIEDUNSPECIFIED
Pashayan, NUNSPECIFIEDUNSPECIFIED
Khaw, KUNSPECIFIEDUNSPECIFIED
Stanford, JLUNSPECIFIEDUNSPECIFIED
Blot, WJUNSPECIFIEDUNSPECIFIED
Thibodeau, SNUNSPECIFIEDUNSPECIFIED
Maier, CUNSPECIFIEDUNSPECIFIED
Kibel, ASUNSPECIFIEDUNSPECIFIED
Cybulski, CUNSPECIFIEDUNSPECIFIED
Cannon-Albright, LUNSPECIFIEDUNSPECIFIED
Brenner, HUNSPECIFIEDUNSPECIFIED
Park, JUNSPECIFIEDUNSPECIFIED
Kaneva, RUNSPECIFIEDUNSPECIFIED
Batra, JUNSPECIFIEDUNSPECIFIED
Teixeira, MRUNSPECIFIEDUNSPECIFIED
Pandha, HSUNSPECIFIEDUNSPECIFIED
Zheng, WUNSPECIFIEDUNSPECIFIED
Date : 4 August 2016
Identification Number : 10.1038/bjc.2016.228
Copyright Disclaimer : (C) 2016 Cancer Research UK. All rights reserved
Uncontrolled Keywords : polyunsaturated fatty acids, prostate cancer, Mendelian randomisation, polygenic risk score, omega-3 fatty acids, omega-6 fatty acids
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 Aug 2016 10:09
Last Modified : 17 Aug 2016 10:09
URI: http://epubs.surrey.ac.uk/id/eprint/811726

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