Dataset Information

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

ABSTRACT: 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.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.Genotypes were determined by ligase detection reaction. HCC patients were newly diagnosed, histopathologically confirmed or previously untreated and controls were cancer-free.Our findings suggest an independent leading contribution of rs17879599 in the 2nd exon of HLA-DRB1 gene to HCC risk in Han Chinese.

SUBMITTER: Shi Y

PROVIDER: S-EPMC5348366 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Shi Yanhui Y Zhai Weiyu W Wang Bin B Zhao Dongmei D Jin He H Wang Yuefei Y Zhang Jidong J An Hongjun H Fu Zhongze Z Zhao Kun K Lu Changzhu C

Oncotarget 20161201 49

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.<h4>Results</h4>All polymorphisms respected the Hardy-Weinberg eq ...[more]

PMID: 27821814

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Project description:BackgroundThe identification of susceptibility genes for specific types of cancer can provide necessary information for the complete characterization of cancer syndromes. Eight single nucleotide polymorphisms (SNPs), rs465498, rs17728461, rs4488809, rs753955, rs13361707, rs9841504, rs2274223, and rs13042395, were reported by genome wide association studies (GWASs) to be closely related to the susceptibility of lung cancer (LC), gastric cancer (GC) or esophageal cancer (EC) in Han population from northern or southern China. However, Chinese Han people from different geographic areas may have different genetic backgrounds. This study aims to assess the genetic associations of the eight SNPs mentioned above with three cancers risk in a Han population from northwest China.MethodsA total of 186 cancer-free controls and 436 cases with non-small cell lung cancer (NSCLC) (159 cases), non-cardia GC (167 cases) or EC (110 cases) were enrolled in this study. Chi-square test and polytomous logistic regression analyses were used to estimate the association between eight cancer-related SNPs and three cancers in a Han Chinese population from northwest China. The logistic regression results were adjusted for confounding factors and Benjamini and Hochberg False Discovery Rate (FDR) method was used to adjust the multiple hypothesis tests. Association analyses by cigarette smoking or alcohol drinking status were analyzed by crossover analyses.ResultsOne of the eight SNPs, rs17728461 was associated with NSCLC susceptibility (in a heterozygous model, OR = 0.44, 95% CI = 0.27-0.72, p = 0.001). Two SNPs, rs753955 and rs13042395, were associated with the risk of non-cardia GC in different genetic models (p < 0.05). No SNPs were associated with EC. The crossover analyses showed that the rs13042395 CT genotype, combined with cigarette smoking or alcohol drinking, could further increase the risk for non-cardia GC (p < 0.05).ConclusionsThese results indicated that rs17728461 may be specifically associated with the risk of NSCLC. rs753955 and rs13042395 were specifically associated with susceptibility to non-cardia GC in Ningxia Han Chinese. Susceptibility-associated polymorphisms in the northwestern Han Chinese were not very consistent with those in the northern Han Chinese or southern Han Chinese. The validation of these findings with a functional evaluation and a larger population is still required.

Dataset Information

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

Publications

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

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