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Blood lipids and prostate cancer: a Mendelian randomization analysis.

Bull, CJ, Bonilla, C, Holly, JM, Perks, CM, Davies, N, Haycock, P, Yu, OH, Richards, JB, Eeles, R, Easton, D, Kote-Jarai, Z, Amin Al Olama, A, Benlloch, S, Muir, K, Giles, GG, MacInnis, RJ, Wiklund, F, Gronberg, H, Haiman, CA, Schleutker, J, Nordestgaard, BG, Travis, RC, Neal, D, Pashayan, N, Khaw, KT, Stanford, JL, Blot, WJ, Thibodeau, S, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Brenner, H, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Micheal, A, Pandha, H, Smith, GD, Lewis, SJ and Martin, RM (2016) Blood lipids and prostate cancer: a Mendelian randomization analysis. Cancer medicine, 5 (6). pp. 1125-1136.

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Abstract

Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.

Item Type: Article
Subjects : Biosciences
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
AuthorsEmailORCID
Bull, CJUNSPECIFIEDUNSPECIFIED
Bonilla, CUNSPECIFIEDUNSPECIFIED
Holly, JMUNSPECIFIEDUNSPECIFIED
Perks, CMUNSPECIFIEDUNSPECIFIED
Davies, NUNSPECIFIEDUNSPECIFIED
Haycock, PUNSPECIFIEDUNSPECIFIED
Yu, OHUNSPECIFIEDUNSPECIFIED
Richards, JBUNSPECIFIEDUNSPECIFIED
Eeles, RUNSPECIFIEDUNSPECIFIED
Easton, DUNSPECIFIEDUNSPECIFIED
Kote-Jarai, ZUNSPECIFIEDUNSPECIFIED
Amin Al Olama, AUNSPECIFIEDUNSPECIFIED
Benlloch, SUNSPECIFIEDUNSPECIFIED
Muir, KUNSPECIFIEDUNSPECIFIED
Giles, GGUNSPECIFIEDUNSPECIFIED
MacInnis, RJUNSPECIFIEDUNSPECIFIED
Wiklund, FUNSPECIFIEDUNSPECIFIED
Gronberg, HUNSPECIFIEDUNSPECIFIED
Haiman, CAUNSPECIFIEDUNSPECIFIED
Schleutker, JUNSPECIFIEDUNSPECIFIED
Nordestgaard, BGUNSPECIFIEDUNSPECIFIED
Travis, RCUNSPECIFIEDUNSPECIFIED
Neal, DUNSPECIFIEDUNSPECIFIED
Pashayan, NUNSPECIFIEDUNSPECIFIED
Khaw, KTUNSPECIFIEDUNSPECIFIED
Stanford, JLUNSPECIFIEDUNSPECIFIED
Blot, WJUNSPECIFIEDUNSPECIFIED
Thibodeau, SUNSPECIFIEDUNSPECIFIED
Maier, CUNSPECIFIEDUNSPECIFIED
Kibel, ASUNSPECIFIEDUNSPECIFIED
Cybulski, CUNSPECIFIEDUNSPECIFIED
Cannon-Albright, LUNSPECIFIEDUNSPECIFIED
Brenner, HUNSPECIFIEDUNSPECIFIED
Park, JUNSPECIFIEDUNSPECIFIED
Kaneva, RUNSPECIFIEDUNSPECIFIED
Batra, JUNSPECIFIEDUNSPECIFIED
Teixeira, MRUNSPECIFIEDUNSPECIFIED
Micheal, AUNSPECIFIEDUNSPECIFIED
Pandha, HUNSPECIFIEDUNSPECIFIED
Smith, GDUNSPECIFIEDUNSPECIFIED
Lewis, SJUNSPECIFIEDUNSPECIFIED
Martin, RMUNSPECIFIEDUNSPECIFIED
Date : June 2016
Identification Number : 10.1002/cam4.695
Copyright Disclaimer : © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords : Cholesterol, Mendelian randomization, Prostate cancer, Statins
Depositing User : Symplectic Elements
Date Deposited : 23 Aug 2016 11:09
Last Modified : 05 Sep 2016 08:03
URI: http://epubs.surrey.ac.uk/id/eprint/811766

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