DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China
DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China
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中国北疆人群DNA多态性与食管鳞癌风险
DOI：
10.3748/wjg.v16.i5.641
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发表时间：
2010-02-07
影响因子：
4.3
通讯作者：
Lu, Xiao-Mei
中科院分区：
文献类型：
--
作者：
Ma, Wen-Jing;Lv, Guo-Dong;Lu, Xiao-Mei
目的：探讨代谢酶和DNA修复基因在食管鳞状细胞癌（ESCC）易感性中的作用。方法：设计病例对照研究，收集128例食管鳞状细胞癌患者和326名性别、年龄和种族匹配的对照受试者的454份样本。代谢酶（醛脱氢酶2、ALDH2；醇脱氢酶1B、ADHB1；细胞色素P450 2A6、CYP2A6）和DNA修复能力基因（切除修复交叉互补组1、ERCC1；O-6-甲基鸟嘌呤DNA甲基转移酶、MGMT、着色性干皮病A组）的69个单核苷酸多态性（SNP）的基因型XPA；着色性干皮病 A 组，XPD）通过 Sequenom MassARRAY 系统测定，并使用根据年龄、性别进行调整的非条件逻辑回归分析结果。 结果：ERCC-1 的变异之间没有关联。 XPA、ADHB1 基因和 ESCC 风险。 ALDH2 中 SNP [Rs886205: 1.626 (1.158-2.284)] 的 C 等位基因、C 等位基因的 XPD [Rs50872: 1.482 (1.058-2.074)] 和 A 等位基因的 MGMT [Rs11016897: 1.666] 的存在频率表明 ESCC 风险增加(1.245-2.228)]。 MGMT 的五个变体与 ESCC 癌变的保护作用相关，包括 C 等位基因 [Rs7069143: 0.698 (0.518-0.939)]、C 等位基因 [Rs3793909: 0.653 (0.429-0.995)]、A 等位基因 [Rs12771882: 0.719 (0.524-0.986)]、C 等位基因 [Rs551491: 0.707 (0.529-0.945)] 和 A 等位基因 [Rs7071825: 0.618 (0.506-0.910)]。在基因型水平上，ALDH2 Rs886205 纯合子携带者发现 ESCC 致癌风险增加[CC 与 TT，比值比 (OR)：3.116，95% CI：1.179-8.234]、MGMT Rs11016879（AA 与 GG，OR：3.112，95% CI： 1.565-6.181)、Rs12771882（AA vs GG，OR：2.442，95% CI：1.204-4.595）和 ALDH2 Rs886205 杂合子携带者（CT vs TT，OR：3.930，95% CI：1.470-10.504）、MGMT分别为 Rs11016879（AG 与 GG，OR：3.933，95% CI：2.216-6.982）和 Rs7075748（CT 与 CC，OR：1.949，95% CI：1.134-3.350）。三种变异与 ESCC 癌变的保护作用相关，MGMT Rs11016878 的携带者（AG 与 AA，OR：0.388，95% CI：0.180-0.836）、Rs7069143（CT 与 CC，OR：0.478，95% CI：0.303-0.754）和Rs7071825（GG 与 AA，OR：0.493，95% CI：0.266-0.915）。 MGMT 中 C 等位基因 [Rs7068306: 2.204 (1.244-3.906)]、A 等位基因 [Rs10734088: 1.968 (1.111-3.484)] 和 C 等位基因 [Rs4751115: 2.178] 的存在频率表明 ESCC 转移风险增加。 (1.251-3.791)]。 CYP2A6 C 等位基因 [Rs8192720: 0.290 (0.099-0.855)] 和 MGMT A 等位基因 [Rs2053139: 0.511 (0,289-0.903)] 存在频率的两个变异与对 ESCC 进展的保护作用相关。 MGMT Rs7068306 杂合子携带者发现 ESCC 转移风险增加（CG 与 CC，OR：4.706，95% CI：1.872-11.833）。结论：ALDH2、XPD 和 MGMT 基因的多态性变异可能对 ESCC 易感性很重要。 CYP2A6 和 MGMT 的多态性变异与 ESCC 转移相关。 (C)2010年百事登。版权所有。
AIM: To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma (ESCC).METHODS: A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects. Genotypes of 69 single nucleotide polymorphisms (SNPs) of metabolic enzyme (aldehyde dehydrogenase-2, ALDH2; alcohol dehydrogenase-1 B, ADHB1; Cytochrome P450 2A6, CYP2A6) and DNA repair capacity genes (excision repair cross complementing group 1, ERCC1; O-6-methylguanine DNA methyltransferase, MGMT, xeroderma pigmentosum group A, XPA; xeroderma pigmentosum group A, XPD) were determined by the Sequenom MassARRAY system, and results were analyzed using unconditional logistic regression adjusted for age, gender.RESULTS: There was no association between the variation in the ERCC-1. XPA, ADHB1 genes and ESCC risk. Increased risk of ESCC was suggested in ALDH2 for frequency of presence C allele of SNP [Rs886205: 1.626 (1.158-2.284)], XPD for C allele [Rs50872: 1.482 (1.058-2.074)], and MGMT for A allele [Rs11016897: 1.666 (1.245-2.228)]. Five variants of MGMT were associated with a protective effect on ESCC carcinogenesis, including C allele [Rs7069143: 0.698 (0.518-0.939)], C allele [Rs3793909: 0.653 (0.429-0.995)], A allele [Rs12771882: 0.719 (0.524-0.986)], C allele [Rs551491: 0.707 (0.529-0.945)], and A allele [Rs7071825: 0.618 (0.506-0.910)]. At the genotype level, increased risk of ESCC carcinogenesis was found in homozygous carriers of the ALDH2 Rs886205 [CC vs TT, odds ratios (OR): 3.116, 95% CI: 1.179-8.234], MGMT Rs11016879 (AA vs GG, OR: 3.112, 95% CI: 1.565-6.181), Rs12771882 (AA vs GG, OR: 2.442, 95% CI: 1.204-4.595),and heterozygotes carriers of the ALDH2 Rs886205 (CT vs TT, OR: 3.930, 95% CI: 1.470-10.504), MGMT Rs11016879 (AG vs GG, OR: 3.933, 95% CI: 2.216-6.982) and Rs7075748 (CT vs CC, OR: 1.949, 95% CI: 1.134-3.350), respectively. Three variants were associated with a protective effect on ESCC carcinogenesis, carriers of the MGMT Rs11016878 (AG vs AA, OR: 0.388, 95% CI: 0.180-0.836), Rs7069143(CT vs CC, OR: 0.478, 95% CI: 0.303-0.754) and Rs7071825 (GG vs AA, OR: 0.493, 95% CI: 0.266-0.915). Increased risk of ESCC metastasis was indicated in MGMT for frequency of presence C allele [Rs7068306: 2.204 (1.244-3.906)], A allele [Rs10734088: 1.968 (1.111-3.484)] and C allele [Rs4751115: 2.178 (1.251-3.791)]. Two variants in frequency of presence C allele of CYP2A6 [Rs8192720: 0.290 (0.099-0.855)] and A allele of MGMT [Rs2053139: 0.511 (0,289-0.903)] were associated with a protective effect on ESCC progression. Increased risk of ESCC metastasis was found in heterozygote carriers of the MGMT Rs7068306 (CG vs CC, OR: 4.706, 95% CI: 1.872-11.833).CONCLUSION: Polymorphic variation in ALDH2, XPD and MGMT genes may be of importance for ESCC susceptibility. Polymorphic variation in CYP2A6 and MGMT are associated with ESCC metastasis. (C) 2010 Baishideng. All rights reserved.