LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China
LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China
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DOI：
10.1093/carcin/bgi071
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发表时间：
2005-07-01
期刊：
影响因子：
4.7
通讯作者：
Ke, Y
中科院分区：
文献类型：
--
作者：
Cao, BW;Tian, XY;Ke, Y
食管癌的特点是不同地理区域之间的发病率差异很大。安阳是华北地区河南省食管癌发病率最高的县。人乳头瘤病毒（HPV）感染与该领域食管癌的病因有关。在这项研究中，我们研究了低分子量多肽（LMP）和转运蛋白与抗原加工（TAP）基因的多态性与食管癌风险的相关性。从肿瘤标本或食管上皮细胞中提取的 DNA 用于检测 HPV 感染。外周血淋巴细胞DNA用于LMP/TAP基因分型。采用聚合酶链反应分析HPV感染情况及LMP/TAP基因多态性。采用非条件logistic回归模型分析LMP/TAP基因多态性与HPV感染对食管癌的联合影响。 TAP2密码子379异亮氨酸携带者和LMP7密码子145赖氨酸携带者被发现更容易患食管癌（TAP2 OR = 2.74, 95% CI 1.15-6.49, P = 0.023; OR = 2.19, 95% CI 1.09-4.37, P = 0.027 LMP7）。携带纯合LMP7/TAP2单倍型C的患者，其在LMP7密码子145处含有谷氨酰胺，在TAP2密码子379处含有异亮氨酸，更容易发生食管癌（OR = 2.96，95 % CI = 1.13-7.81，P = 0.027）。在携带 LMP7/TAP2 单倍型 C 并感染 HPV 的个体中发现对食管癌发展风险的累加效应（OR = 4.33，95% CI = 2.53-7.42，P < 0.0001）。 LMP7/TAP2单倍型C可能是食管癌发生的危险因素，并且可能影响HPV感染个体的肿瘤发生。
Esophageal carcinoma is characterized by a widely ranged incidence variation among the different geographic regions. Anyang is a county in Henan Province of North China with the highest prevalence of esophageal carcinoma. Human papillomavirus (HPV) infection has been linked to the etiology of esophageal cancer in this area. In this study, we investigated correlations of the polymorphisms at low molecular weight polypeptide (LMP) and transporters with antigen processing (TAP) genes, with the risk of esophageal carcinoma. DNA extracted from either tumor specimens or esophageal epithelial cells was used to test HPV infection. Peripheral blood lymphocyte DNA was used for LMP/TAP genotyping. Polymerase chain reaction was performed to analyze HPV infection and LMP/TAP gene polymorphisms. The combined effect of LMP/TAP gene polymorphisms and HPV infection on esophageal carcinoma was analyzed by using unconditional logistic regression models. The TAP2 codons 379 isoleucine carriers and LMP7 codons 145 lysine carriers were found to be more susceptible to esophageal carcinoma (OR = 2.74, 95% CI 1.15-6.49, P = 0.023 for TAP2; OR = 2.19, 95% CI 1.09-4.37, P = 0.027 for LMP7). Patients carrying homozygous LMP7/TAP2 haplotype C, which contained the glutamine at LMP7 codons 145 and the isoleucine at TAP2 codons 379, were more prone to develop esophageal carcinoma (OR = 2.96,95 % CI = 1.13-7.81, P = 0.027). An additive effect on the risk of esophageal carcinoma development was found among individuals carrying LMP7/TAP2 haplotype C and infected by HPV (OR = 4.33, 95% CI = 2.53-7.42, P < 0.0001). LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.