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

Xu Chao,Wei Zhang,Jieqiong Wu,Luyan Zhao,Xuesong Feng,Feng Huang,Chao Jiang

doi:10.1042/bsr20210124

Abstract

Background: Hepatocellular carcinoma (HCC) is a common fatal malignant tumor worldwide. Signal transducer and activator of transcription 4 (STAT4) is HCC susceptibility gene identified by genome-wide association study. The purpose of the present 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: odds ratio (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, 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 (SF).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.

Highlights

Primary hepatocellular carcinoma is a common fatal malignant tumor worldwide, and more than half of the patients have been diagnosed in the middle and advanced stages [1]
The results of HaploReg indicate that the candidate single nucleotide polymorphism (SNP) in the presentstudy were regulated by many factors, such as Promoter histone marks; Enhancer histone marks; Motifs changed; NHGRI/EBI GWAS hits; GRASP QTL hits; Selected eQTL hits
We found no evidence that the remaining three candidate SNPs were associated with Hepatocellular carcinoma (HCC) risk among participants

Summary

Introduction

Primary hepatocellular carcinoma (abbreviated as ‘HCC’) is a common fatal malignant tumor worldwide, and more than half of the patients have been diagnosed in the middle and advanced stages [1]. The occurrence and development of cancer is a complex process with multiple factors, multiple genes and multiple stages It is the result of the combined effect of genetic factors and environmental factors. The purpose of the present 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. Results: The results showed that STAT4 rs11889341 was significantly associated with HCC risk under multiple genetic models (homozygote: odds ratio (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.

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Conclusion