Research Papers:

Genetic susceptibility of eight nonsynonymous polymorphisms in HLA-DRB1 gene to hepatocellular carcinoma in Han Chinese

Yanhui Shi, Weiyu Zhai, Bin Wang, Dongmei Zhao, He Jin, Yuefei Wang, Jidong Zhang, Hongjun An, Zhongze Fu, Kun Zhao and Changzhu Lu _

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Oncotarget. 2016; 7:80935-80942. https://doi.org/10.18632/oncotarget.13111

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Yanhui Shi1, Weiyu Zhai2, Bin Wang3, Dongmei Zhao1, He Jin4, Yuefei Wang3, Jidong Zhang1, Hongjun An1, Zhongze Fu1, Kun Zhao3, Changzhu Lu3

1Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China

2Department of Pharmacy, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China

3Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China

4Department of Cardiology, Hospital of Traditional Chinese Medicine of Qiqihar, Qiqihar, Heilongjiang, China

Correspondence to:

Changzhu Lu, email: [email protected]

Keywords: hepatocellular carcinoma, human leukocyte antigen, non-synonymous polymorphism, genetic predisposition, Han Chinese

Received: September 27, 2016     Accepted: October 28, 2016     Published: November 04, 2016


Backgrounds and Objective: Mounting evidence suggests that human leukocyte antigen (HLA) plays a central role in anti-virus and tumor defense. To test whether genetic variation in HLA-DRB1 gene, a key component of HLA system, can predict its predisposition to hepatocellular carcinoma (HCC), we thereby conducted an association study by genotyping 8 nonsynonymous polymorphisms in HLA-DRB1 gene among 257 HCC patients and 264 controls.

Results: All polymorphisms respected the Hardy-Weinberg equilibrium. The genotypes and alleles of rs17879599 differed significantly between patients and controls after Bonferroni correction (both P < 0.001), and the power to detect this significance was 94.4%. After adjusting for age, gender, smoking, drinking and hepatitis infection, the mutant allele of rs17879702 was significantly associated with an increased risk for HCC under additive (odds ratio [OR] = 2.12, 95% confidence interval [CI]: 1.20-4.02, P = 0.004) and dominant (OR = 2.51, 95% CI: 1.39–2.96, P = 0.004) models. Haplotype analysis indicated that haplotype A-T-C-T-G-C-T-A (alleles ordered by rs199514452, rs201540428, rs201614260, rs17879702, rs17880292, rs17879599, rs17424145 and rs35445101) was overrepresented in patients and enhanced predisposition to HCC (adjusted OR = 2.72, 95% CI: 1.24–5.78, P = 0.004). In cumulative analysis, carriers of 7–9 unfavorable alleles had a 2.41-fold (95% CI: 1.18–4.92, P = 0.016) increased risk for HCC after adjusting for confounding factors relative to those possessing 4 or less unfavorable alleles.

Materials and Methods: Genotypes were determined by ligase detection reaction. HCC patients were newly diagnosed, histopathologically confirmed or previously untreated and controls were cancer-free.

Conclusions: Our findings suggest an independent leading contribution of rs17879599 in the 2nd exon of HLA-DRB1 gene to HCC risk in Han Chinese.

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