Genetic variants in HLA-DP/DQ contribute to risk of cervical cancer: A two-stage study in Chinese women
Genetic variants in HLA-DP/DQ contribute to risk of cervical cancer: A two-stage study in Chinese women
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HLA-DP/DQ 的遗传变异会增加患宫颈癌的风险：一项针对中国女性的两阶段研究
DOI：
10.1016/j.ygyno.2013.02.017
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发表时间：
2013-05-01
影响因子：
4.7
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
--
作者：
Jiang, Jie;Li, Ni;Shen, Hongbing
Objective.人类白细胞抗原（HLA）在将病毒抗原呈递给负责清除病毒感染细胞和肿瘤细胞的免疫细胞中起重要作用。在此，我们评估了MA-DP和HIA-DQ的遗传变异是否与宫颈癌风险相关。我们在一项两阶段病例对照研究中对2317例宫颈癌患者和2109例正常对照进行了HIA-DP（rs3077和rs 9277535）和HIA-DQ（rs 2856718和rs7453920）的4个单核苷酸多态性（SNP）基因分型。我们发现FHA-DP rs3077和rs 9277535与宫颈癌风险增加具有一致的显著相关性（显性遗传模型：rs3077的校正OR = 1.51，95%CI = 132-1.71; rs 9277535的校正OR = 1.29，95%CI = 1.12-1.49）。当联合使用HLA-DP rs3077和rs 9277535时，携带“>= 1”变异等位基因的受试者发生宫颈癌的风险是携带“0”变异等位基因的受试者的1.55倍（95%CI = 1.32-1.81）。宫颈癌风险随着两个SNP的变异等位基因数量的增加而显著增加，呈剂量依赖性（趋势P = 4.33 × 10（-10））。然而，在我们的人群中，HLA-DQ rs 2856718和rs7453920没有显著关联。这些结果表明，HIA-DP rs3077和rs 9277535是中国女性宫颈癌的候选易感性标志物。需要进一步验证不同种族背景的研究，生物学功能分析，特别是HPV分型。(C)2013 Elsevier Inc. All rights reserved.
Objective. Human leukocyte antigens (HLA) play an important role in presenting virus antigens to immune cells that are responsible for the clearance of virus-infected cells and tumor cells. Herein, we evaluated whether genetic variants of MA-DP and HIA-DQ are associated with cervical cancer risk.Methods. We genotyped four single nucleotide polymorphisms (SNPs) in HIA-DP (rs3077 and rs9277535) and HIA-DQ (rs2856718 and rs7453920) in a two-stage case-control study with a total of 2317 cervical cancer cases and 2109 cancer-free controls using TaqMan allelic discrimination assay.Results. We found consistently significant associations of FHA-DP rs3077 and rs9277535 with increased risks of cervical cancer (dominant genetic model: adjusted OR = 1.51, 95% CI = 132-1.71 for rs3077; adjusted OR = 1.29,95% CI = 1.12-1.49 for rs9277535). When combining the effects of HLA-DP rs3077 and rs9277535, subjects carrying ">= 1" variant alleles had a 1.55-fold increased risk of cervical cancer (95% CI = 1.32-1.81), compared with those carrying "0" variant allele. And cervical cancer risk significantly increased with the increasing number of variant alleles of the two SNPs in a dose-dependent manner (P for trend = 4.33 x 10(-10)). However, there were no significant associations for HLA-DQ rs2856718 and rs7453920 in our population.Conclusions. These findings indicate that HIA-DP rs3077 and rs9277535 were candidate susceptibility markers for cervical cancer in Chinese females. Further validation studies with different ethnic background, biological function analyses and especially HPV typing together were needed. (C) 2013 Elsevier Inc. All rights reserved.