Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Pedro Pimentel Nunes (Author) FMUP; Ana Luisa Teixeira (Author) Other; Carina Pereira (Author) Other; Monica Gomes (Author) Other; Catarina Brandao (Author) Other; Catarina Rodrigues (Author) Other; Nadia Goncalves (Author) Other; Ines Boal Carvalho (Author) Other; Roberto Roncon Albuquerque (Author) FMUP; Luis Moreira Dias (Author) Other; Adelino F Leite Moreira (Author) FMUP; Rui Medeiros (Author) ICBAS; Mario Dinis Ribeiro (Author) FMUP

Journal

Title: Digestive and Liver Disease

Vol. 45

Pages: 63-69

ISSN: 1590-8658

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 51 Citations

Scopus - 56 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-002-1C7

DOI: 10.1016/j.dld.2012.08.006

Abstract (EN): Background: Colon carcinogenesis is associated with increased expression levels of Toll-like receptor 2 and Toll-like receptor 4. Aim: To determine in a Caucasian population the role of Toll-like receptor 2 and Toll-like receptor 4 polymorphisms in colorectal cancer development. Methods: Hospital 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-alpha in cell culture and Toll-like receptors levels quantified by real-time RT-PCR. Results: TLR2+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-a production (p = 0.02) with no differences in Toll-like receptors levels. Conclusion: Functional 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7