Analysis of candidate genes in occurrence and growth of colorectal adenomas.

Sylviane Olschwang,Alexandre Pariente,Catherine Bonaiti-Pellié,Déwi Vernerey,Jean Faivre,Jacques Lafon,Vanessa Cottet,Bernard Nalet,Claire Bonithon-Kopp,Pierre Laurent-Puig

doi:10.1155/2009/306786

Abstract

Predisposition to sporadic colorectal tumours is influenced by genes with minor phenotypic effects. A case-control study was set up on 295 patients treated for a large adenoma matched with polyp-free individuals on gender, age, and geographic origin in a 1 : 2 proportion. A second group of 302 patients treated for a small adenoma was also characterized to distinguish effects on adenoma occurrence and growth. We focussed the study on 38 single nucleotide polymorphisms (SNPs) encompassing 14 genes involved in colorectal carcinogenesis. Effect of SNPs was tested using unconditional logistic regression. Comparisons were made for haplotypes within a given gene and for biologically relevant genes combinations using the combination test. The APC p.Glu1317Gly variant appeared to influence the adenoma growth (P = .04, exact test) but not its occurrence. This result needs to be replicated and genome-wide association studies may be necessary to fully identify low-penetrance alleles involved in early stages of colorectal tumorigenesis.

Highlights

Colorectal cancer (CRC) is one of the most common human malignancies in Western countries
We focussed the study on 38 single nucleotide polymorphisms (SNPs) encompassing 14 genes involved in colorectal carcinogenesis
Through a case-control study, the relation between polymorphisms within a series of candidate genes involved in colorectal tumorigenesis and putatively in the formation and the development of colorectal adenomas such carcinogen metabolism enzymes, methylation enzymes, DNA repair genes, oncogenes and tumor suppressor genes [8]

Summary

Introduction

Colorectal cancer (CRC) is one of the most common human malignancies in Western countries. The majority of the cases develop from a premalignant lesion, the adenomatous polyp [1]. Colorectal adenomas have high malignancy potential when they are large in diameter and/or present with severe dysplasia and/or a villous component [2]. Colonoscopic polypectomy has been documented to significantly reduce the incidence of colorectal cancer [3, 4]. The identification of factors associated with the development of colorectal adenoma represents a major goal in colorectal cancer prevention. They could allow the selection of individuals at risk of CRC who may benefit from a screening by colonoscopy

Methods

Results

Conclusion