Single Nucleotide Polymorphisms in STAT3 and STAT4 and Risk of Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B.

Nawin Chanthra,Nutcha Pinjaroen,Sunchai Payungporn,Natthaya Chuaypen,Pisit Tangkijvanich,Kesmanee Piratanantatavorn,Yong Poovorawan

doi:10.7314/apjcp.2015.16.18.8405

Abstract

Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese population. We hypothesized that these polymorphisms might be related to HCC susceptibility in Thai population as well. Study subjects were divided into 3 groups consisting of CHB-related HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The studied SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the distribution of different genotypes for both polymorphisms were in Hardy-Weinberg equilibrium (P>0.05). Our data demonstrated positive association of rs7574865 with HCC risk when compared to healthy controls under an additive model (GG versus TT: odds ratio (OR) =2.07, 95% confidence interval (CI)=1.06-4.03, P=0.033). This correlation remained significant under allelic and recessive models (OR=1.46, 95% CI=1.09-1.96, P=0.012 and OR=1.71, 95% CI=1.13-2.59, P=0.011, respectively). However, no significant association between rs2293152 and HCC development was observed. These data suggest that SNP rs7574865 in STAT4 might contribute to progression to HCC in the Thai population.

Highlights

Liver cancers have been considered as the most cancerrelated death
Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in the Chinese population
Results from recent study have demonstrated that single nucleotide polymorphism (SNP) rs2293152 in STAT3 was significantly associated with an increased risk of HCC in comparison to the subjects without HCC in Chinese population

Summary

Introduction

Liver cancers have been considered as the most cancerrelated death. Accounting for 85% of all primary liver cancers is hepatocellular carcinoma (HCC) (Perz et al, 2006; Subramaniam et al, 2013). Host genetic factors such as signal transducer and activator of transcription (STAT) polymorphisms may contribute to the risk of hepatic carcinogenesis, as accumulated evidences reported that STAT polymorphisms were associated with HBV-related HCC progression (Clark et al, 2013; Jiang et al, 2013; Xie et al, 2013; Kim et al, 2015). Results from recent study have demonstrated that single nucleotide polymorphism (SNP) rs2293152 in STAT3 was significantly associated with an increased risk of HCC in comparison to the subjects without HCC in Chinese population. The impact of this SNP was greater in women when compared to men (Xie et al, 2013)

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