Association of TLR4 gene polymorphism with susceptibility to and prognosis of hepatitis B virus-related primary liver cancer

Objective To investigate the association of TLR4 gene polymorphism with the susceptibility to hepatitis B virus( HBV)-related primary liver cancer and its influence on the prognosis of patients. Methods A total of 106 patients with HBV-related liver cancer who were admitted to Beijing YouAn Hospital which cooperated with Dongzhimen Hospital of Beijing University of Chinese Medicine from June2015 to July 2017 were enrolled as liver cancer group; 120 patients with chronic hepatitis B who were admitted during the same period of time in Dongzhimen Hospital of Beijing University of Chinese Medicine were enrolled as hepatitis B group,and 100 healthy control subjects were enrolled as control group. Blood samples were collected from each group to detect TLR4 D299 G,T399 I,and A896 G polymorphisms,and postoperative recurrence was analyzed for liver cancer patients with different genotypes. An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups. An unconditional logistic regression model and odds ratio( OR) used to estimate relative risk were used to investigate the association of each factor with the onset risk of HBV-related primary liver cancer; the Kaplan-Meier curves were plotted for survival analysis,and the log-rank test was used for comparison of survival curves between groups. Results There were no significant differences in the genotype and allele distributions of TLR4 D299 G and TLR4 A896 G between the three groups( χ2= 1. 436,1. 949,1. 851,and2. 599,all P > 0. 05),while there were significant differences in the genotype and allele distributions of TLR4 T399 I between the three groups( χ2= 11. 654 and 14. 995,both P < 0. 05),and the liver cancer group had a significantly higher frequency of T allele than the hepatitis B group and the control group( P < 0. 05). The unconditional logistic regression model showed that CC genotype of TLR4 T399 I had an OR of 1. 682( 95% confidence interval[CI]: 1. 109-2. 243,P = 0. 027),TT genotype of TLR4 T399 I had an OR of 2. 103( 95% CI:1. 347-2. 896,P < 0. 001),and T allele of TLR4 T399 I had an OR of 1. 872( 95% CI: 1. 192-2. 374,P = 0. 002). There was no significant difference in recurrence-free survival after surgery between the liver cancer patients with different genotypes of TLR4 D299 G and TLR4 A896 G( χ2= 0. 022 and 0. 471,both P > 0. 05). The liver cancer patients with CC genotype of TLR4 T399 I had significantly better recurrence-free survival after surgery than those with CT or TT genotype( χ2= 6. 781,P < 0. 05). Conclusion TLR4 T399 I gene polymorphism is closely associated with the susceptibility to HBV-related primary liver cancer,and T gene of TLR4 T399 I may be an important factor for tumorigenesis and poor prognosis.