Nov 9, 2018

The association between low-density lipoprotein cholesterol predicted by HMGCR genetic variants and breast cancer risk may be mediated by body mass index

BioRxiv : the Preprint Server for Biology
Siddhartha P KarPaul D P Pharoah

Abstract

Orho-Melander et al. recently reported that lower low-density lipoprotein cholesterol (LDLC) as predicted by the T-allele of the variant rs12916 in HMGCR is associated with a decreased risk of developing breast cancer [odds ratio (OR) = 0.89; 95% confidence interval (CI): 0.82-0.96]. This analysis was embedded in a wider Mendelian randomization (MR) study performed using genotype data from a prospective cohort of 26,589 individuals that included 16,022 women and 1176 incident breast cancer cases. HMGCR encodes 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the enzyme inhibited by statins. The T-allele of rs12916 is associated with reduced HMGCR expression and therefore, in principle, its effects should be analogous to the effects of lifelong statin administration starting at birth. The MR study of Orho-Melander et al. also found that a genome-wide LDLC score based on 32 independent LDLC-associated single nucleotide polymorphisms (SNPs) was not associated with breast cancer. In light of this finding, they suggest that the protective effect of the rs12916 T-allele on breast cancer may either be specific to LDLC lowering via genetic inhibition of HMGCR or be the result of a distinct mechanism that is regulated by rs12916 and HMG...Continue Reading

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Mentioned in this Paper

EEF1A2
Genome-Wide Association Study
Study
Mendelian Randomization Analysis
Low Density Lipoprotein Cholesterol Measurement
COG2
Magnetic Resonance Imaging
Genome
HMGCR gene
Administration Procedure

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