Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China

AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. METHODS: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the genealcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. RESULTS: Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence in- terval (CI): 2.76-5.67]. Signif icant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00,95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/ Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). CONCLUSION: The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.

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.