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Blood lipids and prostate cancer: a Mendelian randomization analysis

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Bull, CJ and Bonilla, C and Holly, JM and Perks, CM and Davies, N and Haycock, P and Yu, OH and Richards, JB and Eeles, R and Easton, D and Kote-Jarai, Z and Amin Al Olama, A and Benlloch, S and Muir, K and Giles, GG and MacInnis, RJ and Wiklund, F and Gronberg, H and Haiman, CA and Schleutker, J and Nordestgaard, BG and Travis, RC and Neal, D and Pashayan, N and Khaw, KT and Stanford, JL and Blot, WJ and Thibodeau, S and Maier, C and Kibel, AS and Cybulski, C and Cannon-Albright, L and Brenner, H and Park, J and Kaneva, R and Batra, J and Teixeira, MR and Micheal, A and Pandha, H and Smith, GD and Lewis, SJ and Martin, RM and Fitzgerald, LM, PRACTICAL consortium, Blood lipids and prostate cancer: a Mendelian randomization analysis, Cancer Medicine, 5, (6) pp. 1125-1136. ISSN 2045-7634 (2016) [Refereed Article]


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Copyright 2016 The Authors Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1002/cam4.695

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 Details

Item Type:Refereed Article
Keywords:Blood lipids, prostate cancer, Cholesterol, Mendelian randomization, prostate cancer, statins
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:110627
Year Published:2016
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-05
Last Modified:2017-11-06
Downloads:14 View Download Statistics

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