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dc.contributor.authorBull, Caroline J
dc.contributor.authorBonilla, Carolina
dc.contributor.authorHolly, Jeff MP
dc.contributor.authorPerks, Claire M
dc.contributor.authorDavies, Neil
dc.contributor.authorHaycock, Philip
dc.contributor.authorYu, Oriana Hoi Yun
dc.contributor.authorRichards, J Brent
dc.contributor.authorEeles, Rosalind
dc.contributor.authorEaston, Doug
dc.contributor.authorKote-Jarai, Zsofia
dc.contributor.authorAmin Al Olama, Ali
dc.contributor.authorBenlloch, Sara
dc.contributor.authorMuir, Kenneth
dc.contributor.authorGiles, Graham G
dc.contributor.authorMacInnis, Robert J
dc.contributor.authorWiklund, Fredrik
dc.contributor.authorGronberg, Henrik
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorSchleutker, Johanna
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorTravis, Ruth C
dc.contributor.authorNeal, David
dc.contributor.authorPashayan, Nora
dc.contributor.authorKhaw, Kay-Tee
dc.contributor.authorStanford, Janet L
dc.contributor.authorBlot, William J
dc.contributor.authorThibodeau, Stephen
dc.contributor.authorMaier, Christiane
dc.contributor.authorKibel, Adam S
dc.contributor.authorCybulski, Cezary
dc.contributor.authorCannon-Albright, Lisa
dc.contributor.authorBrenner, Hermann
dc.contributor.authorPark, Jong
dc.contributor.authorKaneva, Radka
dc.contributor.authorBatra, Jyotsna
dc.contributor.authorTeixeira, Manuel R
dc.contributor.authorMicheal, Agnieszka
dc.contributor.authorPandha, Hardev
dc.contributor.authorSmith, George Davey
dc.contributor.authorLewis, Sarah J
dc.contributor.authorMartin, Richard M
dc.contributor.authorPRACTICAL consortium
dc.description.abstractGenetic 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.
dc.description.sponsorshipC. J. B. is funded by the Wellcome Trust 4-year studentship WT083431MA. The Integrative Cancer Epidemiology Programme is supported by Cancer Research UK programme grant C18281/A19169. The MRC IEU is supported by the Medical Research Council and the University of Bristol (MC_UU_12013/1-9). The NIHR Bristol Nutrition Biomedical Research Unit is funded by the National Institute for Health Research (NIHR) and is a partnership between University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The CRUK study and PRACTICAL consortium is supported by the Canadian Institutes of Health Research, European Commission’s Seventh Framework Programme grant agreement no. 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/ A6135. The National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative grant no. 1 U19 CA 148537-01 (the GAME-ON initiative) and NIHR support to the Biomedical Research Centre and The Institute of Cancer Research and Royal Marsden NHS Foundation Trust.
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.subjectMendelian randomization
dc.subjectprostate cancer
dc.titleBlood lipids and prostate cancer: a Mendelian randomization analysis.
dc.description.versionThis is the final version of the article. It first appeared from Wiley via
prism.publicationNameCancer Med
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.contributor.orcidAmin Al Olama, Ali [0000-0002-7178-3431]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idMedical Research Council (MR/N003284/1)
pubs.funder-project-idMedical Research Council (G0401527)

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Attribution 4.0 International
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