Genetic Polymorphisms In TLR9 And Gene-environment Interactions Contribute To Susceptibility Of Primary Liver Cancer In Shunde Population

Objective1. To study the environmental risk factors for primary liver cancer(PLC) inGuangdong Shunde population.2. To investigate the association between genetic variants of toll-like receptor 9 andsuscepitblity to PLC.3. To comprehensively analyse the gene-environment interactions between geneticvariants in TLR4 and TLR9 and environmental factors implicated in thedevelopment of PLC in Guangdong Shunde population. MethodsIn order to explor the risk factor of primary liver cancer(PLC), we conducted a case-control study in Shunde population, included 611 patients with newly diagnosed PLC,and 611 cancer-free controls were also recruited. Unconditional logistic regression analysis and MDR was utilized to investigate the association of TLR9 SNP and the risk of PLC,and to evaluate the role of gene and environment interactions in PLC. Results1. Certain environmental risk factors in primary liver cancer were obversed, including alcohol drinking, experience of drinking pond-ditch water, participating in sports, HBV infectious,the family history of HBV,PLC and cancer. Odds ratio and 95%CI respectively were 1.69(1.28-2.26), 1.62(1.21-2.16), 0.57(0.42-0.78), 13.16(9.75-17.76), 1.52(1.04-2.22), 2.66(1.52-4.66), and 1.47(1.00-2.17).2. The differences in genotype frequencies distribution at rs5743836 between the cases and controls were significant(P=0.0105). Compared with the rs5743836 AA genotype, individuals who carrying AG genotype of rs5743836 may have a increasing risk of PLC(adjusted OR= 1.44;95%CI=1.12-1.84). The differences in haplotype frequencies distribution at ACG consist of rs187084, rs352140 and rs5743836 polymorphisms between the cases and controls was significant(P=0.0125).3. In the gene-environment interaction analysis of the PLC, a significant multiplicative and additive interaction was observed in liver cancer between rs187084 polymorphisms and the family history of liver cancer, between rs352140 polymorphisms and HBV infection. Additionally, multiplicative interaction observed was between rs187084 polymorphisms and alcohol drinking. Also,several additive interaction observed was between rs187084 polymorphisms and HBV infection, rs5743836 polymorphisms and HBV infection, and rs5743836 polymorphisms and the family history of liver cancer. The family history of liver cancer, HBV infection and TLR4-rs10116253 were observed a significant interaction. Conclusions1. The results indicated that several independent risk factors of PLC may be alcohol drinking,drinking pond-ditch water,HBV infection,the family history of HBV and PLC. And participating in sports may be the independent protective factors of PLC.2. Certain association between rs5743836 polymorphisms, ACG haplotype and theoccurrence of PLC was observed if individuals carring AG genotype or ACG haplotype asa risk factor of PLC.3. In the gene-environment interaction analysis of the PLC, several variants of toll-like receptor 9 was observed a significant interaction between HBV infection, alcohol drinking and the family history of liver cancer and HBV infection. Additionally, the family history of liver cancer, HBV infection, TLR4-rs10116253, TLR9-rs187084 and TLR9-rs5743836 were observed a significant interaction.