Role of TLR4 gene polymorphisms in the colorectal cancer risk modulation in ethnic Kashmiri population – A case–control study

Abstract

Background: Colorectal carcinogenesis has been found to be associated with the polymorphic status of Toll-like receptor 4 gene in various populations of the world.

Aim: The aim of the study was to determine the genetic association of TLR4 gene polymorphisms (Asp299Gly and Thr399Ile) with disease susceptibility and risk development in colorectal cancer (CRC) patients of Kashmir, India.

Materials and methods: Genotype frequencies of TLR4 polymorphisms (Asp299Gly and Thr399Ile) were compared between 120 CRC patients and 200 healthy controls using PCRRFLP method.

Results: We did not find any significant association between the TLR4 gene polymorphisms and the CRC cases (p>0.05). However CT genotype (Thr399Ile) showed modest elevated risk of the development of CRC [OR = 1.78 95% CI (0.88–3.5)]. Also G allele (AG genotype) of TLR-4 Asp299Gly polymorphism was found to be significantly associated with the male gender (p value = 0.006) and involvement of Nodes (p value = 0.01) whereas, T allele (CT genotype) of Thr399Ile polymorphism showed significant association with the smoking status (p value = 0.03).

Conclusion: Our results suggest that TLR4 gene polymorphism is not a key modulator of the risk of developing colorectal cancer in Kashmiri population.

Keywords: Colorectal cancer; Kashmir; Polymorphism; RFLP; TLR4