Association Between 3?-UTR MiRNA Binding Site Polymorphisms In LIG4 Gene And Hepatocellular Carcinoma Risk

Objective:Double-strand DNA breaks?DSBs?,one of the most serious forms of DNA damage,contribute to genome instability and thus promote tumorigenesis.LIG4 gene is one of the nonhomologous end-joining?NHEJ?repair pathway genes,which is important in the repair of DSBs.The loss or variant of LIG4 may reduce the DNA repair capacity of NHEJ,and thus contribute to genomic instability and promoting various cancer tumorigenesis.Single-nucleotide polymorphisms?SNPs?in miRNA binding sites may affect the miRNA-mRNA interaction of target genes 3'-untranslated region?3'-UTR?,thereby increase the susceptibility to cancer.This study is to investigate the association between SNPs within the 3'-UTR of LIG4 gene and the risk of HCC.Methods:SNPs in the 3'-UTR of LIG4 gene were selected and assessed for their effects on the risk of HCC in 741 HCC patients and 915 cancer-free controls in a southern Chinese population.The Hardy-Weinberg equilibrium?HWE?was tested by Fisher's exact test for SNPs in controls.The chi-square test was used to compare the differences in demographic characteristics.Adjusted odds ratios?ORs?and its 95%confidence intervals?CIs?were calculated by multivariate logistic regression to evaluate the association between SNPs and the risk of HCC.Results:No significant difference in the genotype frequencies of the LIG4rs10131 was found between the cases and controls?P>0.05?.After adjusted for age,gender,smoking status,drinking status and HBV infection status,there was no obvious relevance of LIG4 rs10131 polymorphisms with hereditary susceptibility of HCC.We further conducted stratified analyses by age,gender,smoking status,drinking status and HBV infection status.Under the recessive genetic model,the CC/CT genotype of LIG4 rs10131 exhibited a 4.30-fold higher risk of HCC?95%CI:1.21-15.30,P=0.024?when compared with the TT genotype among ever-smokers.The CC/CT genotype of LIG4 rs10131 exhibited a 5.58-fold higher risk of HCC?95%CI:1.49-20.88,P=0.011?when compared with the TT genotype among ever-drinkers.Furthermore,the results of logistic regression model showed that LIG4 rs10131 was interactive with both smoking and drinking in the recessive model(P_interaction<0.05).Conclusion:Our study indicated that polymorphisms of LIG4 rs10131 may contribute to the risk of HCC through interaction with smoking/drinking exposures in southern Chinese populations.Further well-designed studies are required to confirm our findings.