Single Nucleotide Polymorphisms within MicroRNAs, MicroRNA Targets, and MicroRNA Biogenesis Genes and Their Impact on Colorectal Cancer Survival

Abstract

We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1115 cases and 1173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status. Multiple comparison adjustments were made using the step-down Bonferroni correction. SNPs associated with survival (P_raw < 0.05) also were assessed with messenger RNA (mRNA). Seven of the 565 SNPs analyzed were associated significantly with CRC survival after adjustment for multiple comparisons. Six of these increased risk of dying, and one, rs12140 (ADAMTS1) decreased risk of dying from CRC (HRR=0.44, 95% CI (0.24, 0.83; P_Holm=0.011). Six SNPs altered colon cancer risk and five were associated with altered mRNA expression across genotypes. One SNP, rs2059691 (PRKRA), was associated with increased mRNA expression and worse survival, and one SNP, rs6598964 (LIN28A), decreased risk of developing colon cancer (OR=0.77 95% CI (0.61, 0.98)) and increased risk of dying from CRC (HRR=2.26 95% CI (1.52, 3.36). P_Holm=0.003). The few SNPs associated with CRC survival, colon cancer risk, or with mRNA expression, resided in genes that influence metastasis and angiogenesis. This article is protected by copyright. All rights reserved.

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