DNA polymorphism and risk of esophageal squamous cell carcinoma in a population of North Xinjiang,China

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 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: 0.6 5 3(0.4 2 9-0.9 9 5)],A a l l e l e[R s 1 2 7 7 1 8 8 2: 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.

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,E...