Association Of Genetic Variants In Toll-like Receptors With The Susceptibility To Gastric Cancer And Their Function In Gastric Cancer

Objectives We explored the association of genetic polymorphisms of TLR3,TLR4,TLR5,TLR7 with the genetic susceptibility to gastric cancer and their function.Methods This case-control study contained 471 gastric cancer(GC)patients and 471 healthy controls.The basic information of each single nucleotide polymorphisms(SNP)was obtained from Ensembl and db SNP database.The potential function change of each SNP was predicted by Alibaba2.1 and SNPinfo.Polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP)analysis and Taq Man real-time PCR assays were used to genotype all samples.The reporter gene activity related with TLR4 3’UTR was analyzed by Dual luciferase reporter gene Assay in BGC823 gastric cancer cells.Results Our results suggested that variant genotypes of TLR4 rs7869402(OR=0.61,95%CI=0.40-0.92,P=0.02)and TLR4 rs7873784(OR=0.17,95%CI=0.09-0.33,P<0.01)gene polymorphisms reduced the susceptibility of GC.Stratified analysis showed that rs7869402 T containing genotype significantly decreased the susceptibility of GC among females(OR=0.38,95%CI=0.16-0.91,P=0.03),older subjects(OR=0.48,95%CI=0.26-0.87,P=0.02),non-smokers(OR=0.41,95%CI=0.23-0.71,P<0.01)and non-drinkers(OR=0.58,95%CI=0.30-0.78,P<0.01).In case of rs7873784 polymorphism,C containing genotype reduced the susceptibility of GC among males(OR=0.08,95%CI=0.03-0.21,P<0.01),but not among females(OR=0.53,95%CI=0.22-1.27,P=0.15).The luciferase activity of rs7869402 T allele was decreased by 29%(P=0.02),the luciferase activity of rs7873784 C allele was decreased by 28%(P=0.02),the luciferase activity of the two alleles were decreased by 48%(P<0.01).Conclusion Our research demonstrates the significance of TLR4 rs7869402 C>T and rs7873784 G>C polymorphisms can decrease the susceptibility of gastric cancer and the luciferase activity.Figure 14;Table 13;Reference 132.