Study of Association Between TLR4 D299G and T399I Polymorphisms and Risk of Gastric Cancer

Introduction:Gastrointestinal cancers constitute more than one-third of the most common cancers and half of the fatal cancers worldwide. Toll-like receptors (TLRs) are identified as pivotal receptors in innate immunity responses. TLR4 is the main receptor that plays a role in lipopolysaccharide  (LPS)  sensing  of  gram-positive  bacteria.  D299G  (rs4986790)  and  T399I (rs4986791) polymorphisms in TLR4 lead to a decrease in immune response against LPS. The current study aimed at investigating the relationship between D299G and T399I polymorphisms and susceptibility to gastritis and gastric precancerous lesions in patients referred to Imam Reza Hospital, Tehran, Iran. Methods:The current case-control study was conducted on 201 individuals consisting of 90 patients with gastric cancer (GC) and 111 healthy controls. Genomic DNA was extracted from peripheral blood and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the mentioned polymorphisms. Results:Allelic frequencies and genetic distribution of polymorphisms were analyzed in the patient and control groups. Although 399C and 299A allele frequencies were higher in the patients`  group,  the  difference  was  not  statistically  significant  (P  >  0.05). Conclusions: No  significant  association  was  observed  between  TLR4  polymorphisms  on positions 299 and 399, and susceptibility to GC. Also no significant correlation was observed between these two polymorphisms and precancerous lesions. The current study results showed that the studied polymorphisms cannot be used as a prognostic marker of GC in Iranian population.

Keywords:

Stomach Neoplasms , TLR4 , Polymorphism , Single Nucleotide