Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma

Xiao-long Wu,1,* Zhi-yu Li,1,* Xin-yu Bi,1 Hong Zhao,1 Jian-jun Zhao,1 Jian-guo Zhou,1 Yue Han,2 Zhen Huang,1 Ye-fan Zhang,1 Jian-qiang Cai1 1Department of Hepatobiliary Surgery, 2Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China *These authors contributed equally to this work Background: Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods: This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results: The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P<0.05). The rs7453920 genotype was significantly associated with the neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a threshold determined by receiver operating characteristic analysis. An elevated NLR was also an independent predictor of OS according to univariate and multivariate analyses (P<0.001). Conclusion: Our data show that HLA gene polymorphisms are associated with SI in patients with HBV-related HCC, and the absence of minor allele A (rs7453920) promotes SI and ­shortens OS. Keywords: human leukocyte antigen, single nucleotide polymorphism, systemic inflammation, hepatitis B virus, hepatocellular carcinom