Dataset Information

A new discovery of STAT4 single nucleotide polymorphisms associated with hepatocellular carcinoma risk in Chinese Han population: a case-control study.

ABSTRACT:

Background

Hepatocellular carcinoma (HCC) is a common fatal malignant tumor worldwide. STAT4 is HCC susceptibility gene identified by genome-wide association study. The purpose of this study was to determine the association between four candidate single nucleotide polymorphisms (SNPs) in STAT4 genes and HCC risk in Chinese Han population.

Methods

A case-control study was conducted to assess the association between STAT4 SNPs and HCC risk in 1011 Chinese Han population. Agena MassARRAY was used to genotype SNPs. The association between SNPs and HCC susceptibility under different genetic models was evaluated by logistic regression analysis. Multifactorial dimension reduction (MDR) analyzed the interaction of 'SNP-SNP' in HCC risk. The difference of clinical characteristics between different genotypes was completed by ANOVA.

Results

The results showed that STAT4 rs11889341 was significantly associated with HCC risk under multiple genetic models (homozygote: OR = 0.60, p = 0.033; recessive: OR = 0.63, p = 0.028; log-additive: OR = 0.83, p = 0.032). The results of subgroup analysis showed that STAT4 rs11889341 is significantly associated with HCC risk with participants who were > 55 years, male or smoking. Both STAT4 rs7574865 and rs10174238 were significantly associated with HCC risk among participants who were > 55 years old, smoking or drinking. STAT4 haplotype (Trs11889341Trs7574865) could reduce the risk of HCC. In addition, rs11889341 and rs7574865 were significantly associated with the level of serum ferritin.

Conclusion

STAT4 rs11889341, rs7574865 or rs10174238 is potentially associated with HCC risk in Chinese Han population. In particular, rs11889341 showed outstanding association with HCC risk.

SUBMITTER: Chao X

PROVIDER: S-EPMC8314431 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer. It is hypothesized that P2RX7 genetic polymorphisms have strong association with HCC susceptibility. Therefore, a case-control study was designed and performed to verify the association between P2RX7 gene polymorphisms and HCC susceptibility. MATERIAL AND METHODS A total of 646 subjects were recruited in our study, including 323 HCC patients and 323 healthy controls. Five gene polymorphisms, -762C>T (rs2393799), 946G>A (rs28360457), 1513A>C (rs3751143), 1068G>A (rs1718119), and 1096C>G (rs2230911), were selected. Odds ratio (ORs) and 95% confidence interval (CI) were used to quantify the association between P2RX7 gene polymorphisms and the susceptibility to HCC. All tests were performed using SPSS 20 and a 2-sided P value of less than 0.05 was considered to be statistically significant. RESULTS Our results suggest that allelic frequencies of these 5 SNPs all conformed to Hardy-Weinberg equilibrium (HWE). There was no significant difference in genotype and allele distributions of -762C>T and 1096C>G between the case group and the control group. However, an increased risk of HCC was associated with 946G>A (A vs. G: OR=1.48, 95%CI=1.09-2.01, P=0.013; GA+AA vs. GG: OR=1.46, 95%CI=1.03-2.07, P=0.033). A similar increased risk was associated with 1513A>C polymorphism (C vs. A: OR=1.37, 95%CI=1.05-1.79, P=0.021; AC+CC vs. AA: OR=1.40, 95%CI=1.01-1.93, P=0.041). On the other hand, a decreased risk of HCC was associated with gene polymorphism of 1068G>A (A vs. G: OR=0.68, 95%CI=0.51-0.91, P=0.010; GA+AA vs. GG: OR=0.68, 95%CI=0.49-0.96, P=0.027; AA vs. GG: OR=0.42, 95%CI=0.18-0.99, P=0.048). CONCLUSIONS Our results suggest that 3 of the 5 polymorphisms of P2RX7 described above (1513A>C, 946G>A, and 1068G>A) are significantly associated with HCC susceptibility in a Chinese Han population. Studies with larger sample sizes are recommended to confirm whether our results will be applicable to different ethnic populations in China.