Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Feb 7, 2010; 16(5): 641-647
Published online Feb 7, 2010. doi: 10.3748/wjg.v16.i5.641
DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang, China
Wen-Jing Ma, Guo-Dong Lv, Shu-Tao Zheng, Cong-Gai Huang, Qing Liu, Xing Wang, Ren-Yong Lin, Ilyar Sheyhidin, Xiao-Mei Lu
Wen-Jing Ma, Guo-Dong Lv, Shu-Tao Zheng, Cong-Gai Huang, Qing Liu, Xing Wang, Ren-Yong Lin, Xiao-Mei Lu, Medical Research Center, the First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Ilyar Sheyhidin, Department of Thoracic Surgery, the First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Author contributions: Ma WJ, Lv GD and Zheng ST performed the majority of experiments; Huang CG, Liu Q and Wang X provided vital reagents and analytical tools and were involved in editing the manuscript; Lin RY and Sheyhidin I coordinated in the collection of all the human material; Lu XM designed the study and wrote the manuscript in addition to providing financial support for this work.
Supported by The National Natural Science Foundation of China, No. 30760223, 30860097, the First Affiliated of Xinjiang Medical University Grant, No. 2008-YFY-01, Xinjiang Science and Technology Bureau Grant, No. 200511113, and Urumqi Science and Technology Bureau Grant, No. Y05331002
Correspondence to: Xiao-Mei Lu, Professor, Medical Research Center, the First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China. luxiaomei88@163.com
Telephone: +86-991-4360051 Fax: +86-991-4360051
Received: September 22, 2009
Revised: November 19, 2009
Accepted: November 26, 2009
Published online: February 7, 2010
Abstract

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; O6-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 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).

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.

Keywords: Esophageal cancer; Metabolic enzyme gene; DNA repair gene; Carcinogenesis; Metastasis