Abstract

Single nucleotide polymorphisms (SNPs) in immune related gene may influence the susceptibility of cancer. We selected inducible T cell costimulator (ICOS) rs4404254 T>C, rs10932029 T>C, CD28 rs3116496 T>C and CD80 rs7628626 C>A SNPs and assessed the potential relationship of these SNPs with hepatocellular carcinoma (HCC) risk. A total of 584 HCC cases and 923 healthy controls were recruited. And SNPscan™ genotyping assay was used to obtain the genotypes of ICOS, CD28 and CD80 polymorphisms. We found that ICOS rs10932029 T>C polymorphism significantly increased the risk of HCC (additive model: adjusted odds ratio (OR), 1.59; 95% confidence interval (CI), 1.13–2.22; P=0.007; homozygote model: adjusted OR, 1.12; 95% CI, 0.31–4.03; P=0.867; dominant model: adjusted OR, 1.58; 95% CI, 1.14–2.19; P=0.007 and recessive model: adjusted OR, 1.02; 95% CI, 0.28–3.68; P=0.974). However, ICOS rs4404254 T>C, CD28 rs3116496 T>C and CD80 rs7628626 C>A SNPs were not associated with the risk of HCC. To evaluate the effects of ICOS rs10932029 T>C on HCC risk according to different age, gender, chronic hepatitis B virus (HBV) infection, tobacco consumption and drinking status, we carried out a stratification analysis. We found that ICOS rs10932029 T>C polymorphism might increase the risk of HCC in male, ≥53 years, never smoking, never drinking and non-chronic HBV infection subgroups. Our study highlights that ICOS rs10932029 T>C polymorphism may confer the susceptibility to HCC. It may be beneficial to explore the relationship between variants in immune related genes and the development of HCC.

Highlights

  • Hepatocellular carcinoma (HCC) remains a major public health problem worldwide, especially in China. [1] The etiology of HCC is very complicated

  • The minor allele frequencies (MAFs) of inducible T cell costimulator (ICOS) rs4404254 T>C, rs10932029 T>C, CD28 rs3116496 T>C and CD80 rs7628626 C>A were similar to the data for Chinese Han population

  • After adjustment by logistic regression analysis with these risk factors, we found that ICOS rs10932029 T>C polymorphism might be associated with an increased risk of HCC in some subgroups [male group: TC vs. TT: adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) 1.01–2.12, P=0.043 and TC/CC vs. TT: adjusted OR = 1.49, 95% CI 1.04–2.13, P=0.031; ≥53 years subgroup: TC vs. TT: adjusted OR = 1.70, 95% CI 1.09–2.64, P=0.020 and TC/CC vs. TT: adjusted OR = 1.62, 95% CI 1.05–2.49, P=0.029; never smoking group: TC/CC vs. TT: adjusted OR = 1.49, 95% CI 1.00–2.22, P=0.049 and never drinking group: TC vs. TT: adjusted OR = 1.56, 95% CI 1.07–2.26, P=0.020 and TC/CC vs. TT: adjusted OR = 1.57, 95% CI 1.09–2.26, P=0.016 and non-chronic hepatitis B virus (HBV) infection group:

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Summary

Introduction

Hepatocellular carcinoma (HCC) remains a major public health problem worldwide, especially in China. [1] The etiology of HCC is very complicated. [1] The etiology of HCC is very complicated. It is reported that many environmental factors and unhealthy lifestyles may influence the development and progress of HCC. The potential risk factors contributing to HCC are chronic hepatitis B virus (HBV) infection, aflatoxin, foods preserved by salting, smoking and drinking et al [2,3,4] a growing number of investigations have focused on the etiology of HCC, it is not fully understood. It is suggested that an individual’s hereditary factor is implicated in pathogenesis of HCC. A number of studies reported that some immune related gene variants might play important roles in the development of HCC [5,6,7]

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