Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomas

Abstract

Three polymorphic sites at chromosome 8q24 (rs7837328, rs10808555, rs6983267) have been associated with risk for colorectal adenomas. It was also previously reported that the single nucleotide polymorphism (SNP) rs6983267 may enhance Wnt signaling, which regulates cell proliferation. To investigate associations between the 8q24 variants and colorectal epithelial cell proliferation in the normal-appearing colorectal mucosa, as well as with colorectal adenoma, we analyzed data from a previously conducted pilot, colonoscopy-based case-control study of incident, sporadic colorectal adenoma (n = 90 cases, 132 controls). Proliferation was measured in biopsies of the normal-appearing mucosa of the rectum, sigmoid colon, and cecum using immunohistochemistry for proliferating cell nuclear antigen (PCNA). The direct associations of each SNP with colorectal adenoma were consistent with those in previous reports. For all three SNPs, proliferation tended to be higher among those homozygous for the risk alleles compared to those heterozygous or homozygous for the nonrisk alleles combined; among the controls, proliferation was 32.1% higher (P = 0.23) for those with the rs10808555 GG genotype, 16.4% higher (P = 0.16) for those with the rs7837328 AA genotype, and 6.5% higher (P = 0.52) for those with the rs6983267 GG genotype. These preliminary findings, which are consistent with previously reported direct associations between genetic variants at chromosome 8q24 and risk for colorectal adenoma, suggest that the genetic variants may also be associated with higher levels of colorectal epithelial cell proliferation, thus providing support for further investigation of the hypothesis that 8q24 variants may increase risk via enhanced Wnt signaling.