Nov 23, 2017

Blood lipid genetic scores, the HMGCR gene and cancer risk: a Mendelian randomization study

International Journal of Epidemiology
Marju Orho-MelanderTanja Stocks

Abstract

It is unclear whether there are causal associations between blood lipids, statin use and cancer risks. Under certain assumptions, Mendelian randomization analysis of a genetic marker for an exposure eliminates reverse causation and confounding. We applied Mendelian randomization analysis to genetic scores, comprising 26-41 single-nucleotide polymorphisms (SNPs), as instrumental variables (IVs) for triglycerides and low- and high-density lipoprotein cholesterol (LDLC, HDLC), using a prospective cohort of 26 904 individuals in which there were 6607 incident cancers. We also investigated cancer risk for a SNP (rs12916) in the gene encoding hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the targeted enzyme in statin treatment. We used logistic regression and SNP pleiotropy-adjusted analyses to estimate the odds ratio per standard deviation (OR). The OR for the triglyceride IV as a predictor of any cancer was 0.91 [95% confidence interval (CI): 0.80-1.03] unadjusted, and 0.87 (95% CI: 0.78-0.95) from the pleiotropy-adjusted analysis. For the HMGCR rs12916 per LDLC-lowering T-allele, the OR was 1.09 (95% CI: 1.01-1.18) for prostate cancer and 0.89 (95% CI: 0.82-0.96) for breast cancer. The LDLC IV was not associated with pros...Continue Reading

  • References44
  • Citations7

References

Mentioned in this Paper

Biological Markers
Prostatic Neoplasms
Hypoalphalipoproteinemia, Familial
Mendelian Randomization Analysis
Low Density Lipoprotein Cholesterol Measurement
COG2
Neoplasm of Uncertain or Unknown Behavior of Bladder
Lung
Genes
Coenzyme A

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