TAP1基因第637位密码子杂合子降低哈萨克族人群对HPV感染的易感性，但增加其患食管癌的易感性。

Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but increases susceptibility to esophageal cancer among the Kazakh populations.

作者信息

Zou Ningjing, Yang Lan, Chen Ling, Li Tingting, Jin Tingting, Peng Hao, Zhang Shumao, Wang Dandan, Li Ranran, Liu Chunxia, Jiang Jinfang, Wang Lianghai, Liang Weihua, Hu Jianming, Li Shugang, Wu Chuanyue, Cui Xiaobin, Chen Yunzhao, Li Feng

机构信息

Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, North 4th Road, Shihezi, Xinjiang, 832002, China.

Department of Pathology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.

出版信息

J Exp Clin Cancer Res. 2015 Jul 25;34(1):70. doi: 10.1186/s13046-015-0185-y.

DOI:10.1186/s13046-015-0185-y

PMID:26205887

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4514451/

Abstract

BACKGROUND

The role of human papillomavirus (HPV) may be involved in the development of esophageal cancer (EC) and the polymorphic immune response gene transporter associated with antigen processing (TAP) may be involved in HPV persistence and subsequent cancer carcinogenesis. The current study aims to provide association evidence for HPV with EC, to investigate TAP1 polymorphisms in EC and assess its association with HPV statuses and EC in Kazakhs.

METHODS

The HPV genotypes in 361 patients with EC and 66 controls selected from Kazakh population were evaluated using PCR. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to detect two SNPs of TAP1 in 150 cases comprised of 75 HPV(+) and 75 HPV(-) patients and 283 pure ethnic population of Kazakh and evaluate their associations with susceptibility to EC. A case-to-case comparison based on the genotyping results was conducted to address the function of TAP1 variants in the involvement of HPV.

RESULTS

The presence of four HPV genotypes in EC tissues - including HPV 16, 18, 31, 45 - was significantly higher at 64.6 % than those in controls at 18.2 % (P < 0.001). Such presence was strongly associated with increased risk of EC (OR 8.196; 95 % CI 4.280-15.964). The infection of HPV16, and multi-infection of 16 and 18 significantly increase the risk for developing EC (OR 4.616, 95 % CI 2.099-10.151; and OR 6.029, 95 % CI 1.395-26.057 respectively). Heterozygote of TAP1 D637G had a significantly higher risk for developing EC (OR 1.626; 95 % CI 1.080-2.449). The odds ratio for HPV infection was significantly lower among carriers of TAP1 D637G polymorphism (OR 0.281; 95 % CI 0.144-0.551).

CONCLUSIONS

HPV infection exhibits a strong positive association with the risk of EC in Kazakhs. Heterozygote of TAP1 D637G decreases susceptibility to HPV infection in patients with EC but increases susceptibility to EC among the Kazakh populations.

摘要

背景

人乳头瘤病毒（HPV）可能参与食管癌（EC）的发生发展，与抗原加工相关的多态性免疫反应基因转运体（TAP）可能参与HPV持续感染及后续癌症的发生。本研究旨在提供HPV与EC相关性的证据，调查EC患者中TAP1基因多态性，并评估其与哈萨克族人群HPV状态及EC的相关性。

方法

采用聚合酶链反应（PCR）对从哈萨克族人群中选取的361例EC患者和66例对照者的HPV基因型进行评估。对150例患者（包括75例HPV阳性和75例HPV阴性患者）及283例纯正哈萨克族人群进行聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP），以检测TAP1的两个单核苷酸多态性（SNP），并评估它们与EC易感性的相关性。根据基因分型结果进行病例对照比较，以探讨TAP1变异体在HPV参与过程中的作用。

结果

EC组织中四种HPV基因型（包括HPV 16、18、31、45）的存在率为64.6%，显著高于对照组的18.2%（P<0.001）。这种存在与EC风险增加密切相关（比值比8.196；95%可信区间4.280-15.964）。HPV16感染以及16和18型的多重感染显著增加了发生EC的风险（比值比分别为4.616，95%可信区间2.099-10.151；以及6.029，95%可信区间1.395-26.057）。TAP1 D637G杂合子发生EC的风险显著更高（比值比1.626；95%可信区间1.080-2.449）。TAP1 D637G多态性携带者中HPV感染的比值比显著更低（比值比0.281；95%可信区间0.144-0.551）。