Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population

AIM:To investigate toll-like receptor 2(TLR2)-196 to-174 del,and TLR4(+896A/G rs4986790 and +1196C/T rs4986791) polymorphisms at risk of chronic gastritis and gastric cancer in a Brazilian population and association of gastric lesions with risk factors such as smoking,alcohol intake and Helicobacter pylori infection.METHODS:In this case-control study,polymorphism at TLR2-196 to-174 del was investigated by using the allele-specific polymerase chain reaction(PCR) method,while the PCR-restriction fragment length polymorphism technique was carried out to identify the TLR4(rs4986790 and rs4986791) genotypes in 607 Brazilian individuals(208 with chronic gastritis-CG,174 with gastric cancer-GC and 225 controls-C).RESULTS:The single nucleotide polymorphisms TLR4 +1196C/T was not associated with risk of chronic gastritis or gastric cancer and the homozygous genotypes TLR4 +896GG and TLR4 +1196TT were absent in the studied population.However,the frequency of TLR2-196 to-174 ins/del + del/del and TLR4 +896AG genotypes was significantly higher(P < 0.01 and P = 0.01,respectively) in the cancer group(33.4% and 11.5%,respectively) than in the control group(16.9% and 4.5%,respectively).It was also observed that the G-C haplotype of the TLR4 +896A/G+1196C/T(P = 0.02) and the combination of variant alleles of the TLR2 /TLR4 +896G(P = 0.02) are associated with susceptibility to gastric cancer.In addition,the multiple logistic regression showed that male gender [odds ratio(OR) = 2.70;95% CI:1.66-4.41;P < 0.01],alcohol intake(OR = 2.93;95% CI:1.76-4.87;P < 0.01),TLR2-196 to-174 del(OR = 2.64;95% CI:1.56-4.44;P < 0.01) and TLR4 +896G(OR = 3.19;95% CI:1.347.61;P < 0.01) polymorphisms were associated with a higher susceptibility to developing this neoplasm.CONCLUSION:Our data indicate that TLR2-196 to-174 del and TLR4 +896G may increase the risk of gastric cancer in a Brazilian population.