Title: MicroRNA polymorphisms and risk of colorectal cancer.
Authors: Schmit, Stephanie L; Gollub, Jeremy; Shapero, Michael H; Huang, Shu-Chen; Rennert, Hedy S; Finn, Andrea; Rennert, Gad; Gruber, Stephen B
Published In Cancer Epidemiol Biomarkers Prev, (2015 Jan)
Abstract: miRNAs act as post-transcriptional regulators of gene expression. Genetic variation in miRNA-encoding sequences or their corresponding binding sites may affect the fidelity of the miRNA-mRNA interaction and subsequently alter the risk of cancer development.This study expanded the search for miRNA-related polymorphisms contributing to the etiology of colorectal cancer across the genome using a novel platform, the Axiom miRNA Target Site Genotyping Array (237,858 markers). After quality control, the study included 596 cases and 429 controls from the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study of colorectal cancer in northern Israel. The association between each marker and colorectal cancer status was examined assuming a log-additive genetic model using logistic regression adjusted for sex, age, and two principal components.Twenty-three markers had P values less than 5.0E-04, and the most statistically significant association involved rs2985 (chr6:34845648; intronic of UHRF1BP1; OR = 0.66; P = 3.7E-05). Furthermore, this study replicated a previously published risk locus, rs1051690, in the 3'-untranslated region of the insulin receptor gene INSR (OR = 1.38; P = 0.03), with strong evidence of differences in INSR gene expression by genotype.This study is the first to examine associations between genetic variation in miRNA target sites and colorectal cancer using a genome-wide approach. Functional studies to identify allele-specific effects on miRNA binding are needed to confirm the regulatory capacity of genetic variation to influence risk of colorectal cancer.This study demonstrates the potential for an miRNA-targeted genome-wide association study to identify candidate susceptibility loci and prioritize them for functional characterization.
PubMed ID: 25342389
MeSH Terms: Aged; Colorectal Neoplasms/genetics*; Female; Humans; Male; MicroRNAs; Polymorphism, Genetic; Risk