| Objective: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of death from cancer. The overall 5-year survival rate of HCC is less than 5%. Chronic infection with hepatitis B virus (HBV) is the major risk factor for the development of HCC in china,70% of HCC was HBsAg positive. The risk of developing HCC in HBV infected patients may be 100 times higher than that in the uninfected persons. However, only 1-5% of the infected patients will develop HCC. Additionally, the occurrence of HCC shows familial aggregation, and is associated with family history. All these imply that genetic susceptibility also plays a vital role in developing HCC. Accumulating evidence shows that STAT3 and XRCC4 gene polymorphisms are associated with tumor occurrence. To investigate their association with HCC, we choose 2 SNPs of signal transducer and activators of transcription 3 (STAT3) rs2293152 and X-ray repair cross complementing group 4 (XRCC4) rs1805377 to investigate their susceptibility with HCC.Methods:This was a hospital-based case-control study. A total of 200 HCC patients defined by the imaging examination and/or histopathology (165 patients), and 207 HBsAg-positive non-HCC controls were recruited with matched genders and ages. Genomic DNA was extracted from 2-3 ml peripheral blood samples using phenol/chloroform protocols after the cells were digested by proteinase K. Two common SNPs of STAT3 and XRCC4 gene were genotyped with polymerase chain reaction combined with restriction fragment length polymorphism method (PCR-RFLP), and direct DNA sequencing was performed to validate the accuracy. All data were analyzed statistically in SPSS software. Student’s t-test was used to compare quantitiative data, while categorical data were compared with the use of the chi-square test or Fisher’s exact propability, Odd ratio and 95% confidence interval indicate relative risk scale. The Hardy-Weinberg equilibrium was tested by a goodness-of-fit chi-square to compare the observed genotype frequencies with the expected ones among the control subjects.Results:There are a total of 200 HBV-related HCC patients in the case group, including 173 (86.5%) males and 27 (13.5%) females, their mean±SD age of 52.28±10.91 years.The control group consisted of 207 HBV-infected non-HCC patients, including 168 (81.2%) males and 39 (18.8) females, mean±D age of 51.62±13.51 years. The accuracy of PCR-RFLP was validated by direct DNA sequencing. The goodness-of-fit chi-square test was made to confirm the Hardy-Weinberg equilibrium among control group. The distribution difference in age and sex were not significant between the case and control group.The genotype frequencies of STAT3 rs2293152 were 33.5% for GG,49.5% for GC and 17% for CC in the HCC patients, while those were 25.1% for GG,56.5% for GC and 18.4% for CC respectively in control group (P= 0.174). The differences of the allele mutation frequencies of STAT3 rs2293152 were also not significant between the two groups, G allele frequency was 58.25%, C allele for 41.75% in the case group, and 53.4% for G allele,46.6% for C allele in the control group (P= 0.162). The genotype frequencies of XRCC4 rs1805377 were 61% for AA, 30% for GA and 9% for GG in case group, while those were 59.9% for AA,31.9% for GA and 8.2% for GG in control group (P= 0.900). The allele frequencies of XRCC4 rs1805377 were 76% for A allele,24% for G allele in case group, and 75.8% for A allele,24.2% for G allele in control group (P= 0.959). Both of the allele and genotype distribution frequencies of STAT3 rs7574865 and XRCC4 rs1805377 showed no difference between the case and control groups.Odd ratio and 95% confidence interval were measured to evaluate their susceptibility with HCC. The genotypes of STAT3 rs2293152 were not associated with the individual risk of HBV related HCC (GG vs GC+CC, OR= 1.502,95% CI= 0.977-2.308, P=0.063; GC vs GG+CC, OR= 0.754,95% CI= 0.510-1.114, P= 0.156; CC vs GG+GC, OR= 0.911,95% CI= 0.547-1.517, P= 0.720). The genotypes of XRCC4 rs1805377 had no correlations of individual risk of HBV related HCC (AA vs GA+GG, OR= 1.047,95% CI= 0.704-1.558, P= 0.821; GA vs AA+GG, OR= 0.916,95% CI=0.601-1.394, P= 0.681; GG vs AA+GA, OR= 1.07,95% CI = 0.535-2.140, P= 0.848). After stratified by sex, the genotypes of the two snps remain showed no correlations of risk of HBV related HCC.Conclusion:Although other studies suggest that the polymorphisms of STAT3 rs7574865 and XRCC4 rs1805377 may be associated with HCC susceptibility. However, the results in the present study did not find the evidence to support the association between the the polymorphisms of STAT3 rs7574865 or XRCC4 rs1805377 and the HCC susceptibility. |
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