Medical Research Center, the First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
World J Gastroenterol. 2010 Feb 7;16(5):641-7. doi: 10.3748/wjg.v16.i5.641.
To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma (ESCC).
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.
There was no association between the variation in the ERCC1, 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).
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.
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。
采用病例对照研究设计，纳入 128 例 ESCC 患者和 326 名性别、年龄和种族匹配的对照，共 454 例样本。采用Sequenom MassARRAY 系统检测 69 个单核苷酸多态性（SNP）的代谢酶（乙醛脱氢酶 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，XPA；着色性干皮病 A 组，XPD）的基因型，并通过条件 logistic 回归模型分析其与 ESCC 风险的关系。
ERCC1、XPA、ADHB1 基因的变异与 ESCC 风险无关。ALDH2 中 C 等位基因频率[Rs886205：1.626（1.158-2.284）]、XPD 中 C 等位基因频率[Rs50872：1.482（1.058-2.074）]和 MGMT 中 A 等位基因频率[Rs11016897：1.666（1.245-2.228）]与 ESCC 风险增加相关。MGMT 的 5 个变异与 ESCC 癌变的保护作用相关，包括 C 等位基因频率[Rs7069143：0.698（0.518-0.939）]、C 等位基因频率[Rs3793909：0.653（0.429-0.995）]、A 等位基因频率[Rs12771882：0.719（0.524-0.986）]、C 等位基因频率[Rs551491：0.707（0.529-0.945）]和 A 等位基因频率[Rs7071825：0.618（0.506-0.910）]。在基因型水平上，ALDH2 Rs886205 纯合子携带者（CC 与 TT，比值比[OR]：3.116，95%置信区间[CI]：1.179-8.234）、MGMT Rs11016879 杂合子携带者（AA 与 GG，OR：3.112，95%CI：1.565-6.181）、Rs12771882 杂合子携带者（AA 与 GG，OR：2.442，95%CI：1.204-4.595）和 ALDH2 Rs886205 杂合子携带者（CT 与 TT，OR：3.930，95%CI：1.470-10.504）、MGMT Rs11016879 杂合子携带者（AG 与 GG，OR：3.933，95%CI：2.216-6.982）和 Rs7075748 杂合子携带者（CT 与 CC，OR：1.949，95%CI：1.134-3.350）与 ESCC 转移风险增加相关。MGMT 的 3 个变异与 ESCC 癌变的保护作用相关，包括 Rs11016878 杂合子携带者（AG 与 AA，OR：0.388，95%CI：0.180-0.836）、Rs7069143 杂合子携带者（CT 与 CC，OR：0.478，95%CI：0.303-0.754）和 Rs7071825 杂合子携带者（GG 与 AA，OR：0.493，95%CI：0.266-0.915）。MGMT 中 C 等位基因频率[Rs7068306：2.204（1.244-3.906）]、A 等位基因频率[Rs10734088：1.968（1.111-3.484）]和 C 等位基因频率[Rs4751115：2.178（1.251-3.791）]与 ESCC 转移风险增加相关。CYP2A6 中 C 等位基因频率[Rs8192720：0.290（0.099-0.855）]和 MGMT 中 A 等位基因频率[Rs2053139：0.511（0.289-0.903）]与 ESCC 进展的保护作用相关。MGMT Rs7068306 杂合子携带者（CG 与 CC，OR：4.706，95%CI：1.872-11.833）与 ESCC 转移风险增加相关。
ALDH2、XPD 和 MGMT 基因的多态性可能与 ESCC 易感性有关。CYP2A6 和 MGMT 的多态性与 ESCC 转移相关。
