TY - JOUR
T1 - Polyunsaturated fatty acids and prostate cancer risk
T2 - A Mendelian randomisation analysis from the PRACTICAL consortium
AU - Khankari, Nikhil K.
AU - Murff, Harvey J.
AU - Zeng, Chenjie
AU - Wen, Wanqing
AU - Eeles, Rosalind A.
AU - Easton, Douglas F.
AU - Kote-Jarai, Zsofia
AU - Al Olama, Ali Amin
AU - Benlloch, Sara
AU - Muir, Kenneth
AU - Giles, Graham G.
AU - Wiklund, Fredrik
AU - Gronberg, Henrik
AU - Haiman, Christopher A.
AU - Schleutker, Johanna
AU - Nordestgaard, BØrge G.
AU - Travis, Ruth C.
AU - Donovan, Jenny L.
AU - Pashayan, Nora
AU - Khaw, Kay Tee
AU - Stanford, Janet L.
AU - Blot, William J.
AU - Thibodeau, Stephen N.
AU - Maier, Christiane
AU - Kibel, Adam S.
AU - Cybulski, Cezary
AU - Cannon-Albright, Lisa
AU - Brenner, Hermann
AU - Park, Jong
AU - Kaneva, Radka
AU - Batra, Jyotsna
AU - Teixeira, Manuel R.
AU - Pandha, Hardev
AU - Zheng, Wei
N1 - Funding Information:
Dr Nikhil K Khankari was supported by NIH grant R25CA160056.
Publisher Copyright:
© 2016 Cancer Research UK.
PY - 2016/8/23
Y1 - 2016/8/23
N2 - 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.
AB - 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.
KW - polyunsaturated fatty acids; prostate cancer; Mendelian randomisation; polygenic risk score; omega-3 fatty acids; omega-6 fatty acids
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U2 - 10.1038/bjc.2016.228
DO - 10.1038/bjc.2016.228
M3 - Article
C2 - 27490808
AN - SCOPUS:84982918768
SN - 0007-0920
VL - 115
SP - 624
EP - 631
JO - British journal of cancer
JF - British journal of cancer
IS - 5
ER -