Article ID Journal Published Year Pages File Type
3263046 Digestive and Liver Disease 2013 7 Pages PDF
Abstract

BackgroundColon carcinogenesis is associated with increased expression levels of Toll-like receptor 2 and Toll-like receptor 4.AimTo determine in a Caucasian population the role of Toll-like receptor 2 and Toll-like receptor 4 polymorphisms in colorectal cancer development.MethodsHospital based multicentre case control study involving 193 colorectal cancer patients and 278 healthy individuals. DNA samples were extracted from blood cells and genotyping of TLR2+597T>C, TLR2−4760T>C, TLR4−3745A>G, TLR2Arg753Gln, TLR4Asp299Gly was performed. Functionality of risk polymorphisms was evaluated through production of TNF-α in cell culture and Toll-like receptors levels quantified by real-time RT-PCR.ResultsTLR2+597CC homozygous had 5-fold decreased risk (odds ratio (OR) = 0.21, 95% CI: 0.09–0.50, p < 0.001) and TLR4 299Gly homozygous 3-fold increased risk of colorectal cancer (OR = 3.30, 95% CI: 1.18–9.28, p = 0.015). In stratified analysis, TLR2+597CC genotype protective effect was even higher in overweight individuals (OR = 0.17, 95% CI: 0.06–0.53, p < 0.001) and in never smokers (OR = 0.11, 95% CI: 0.02–0.51, p = 0.001). Also, the increased risk effect for TLR4 299Gly homozygous genotype was higher in overweight individuals (OR = 8.67, 95% CI: 1.11–87.85, p = 0.011). TLR2+597T>C polymorphism conferred 41% less (p = 0.03) and TLR4Asp299Gly 65% more TNF-α production (p = 0.02) with no differences in Toll-like receptors levels.ConclusionFunctional Toll-like receptor 2 and Toll-like receptor 4 polymorphisms significantly alter the risk to have colorectal cancer. Obesity and smoking may influence the risk for colorectal cancer in individuals presenting these genetic profiles.

Related Topics
Health Sciences Medicine and Dentistry Endocrinology, Diabetes and Metabolism
Authors
, , , , , , , , , , , ,