Association between polymorphisms in the CYP1A1, CYP2E1 and GSTM1 genes, and smoking, alcohol and upper digestive tract carcinomas in a high-incidence area of northern China.

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 (CYP1A1) rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 (CYP2E1) rs2031920 C>T polymorphism increased EC risk, while the GSTM1 null genotype decreased EC risk. An association existed between the following: CYP1A1 rs4646903 and smoking in EC, GCC and GAC; CYP1A1 rs4646903 and alcohol consumption in EC and GCC; CYP2E1 rs2031920 and smoking in EC, GCC and GAC and CYP2E1 rs2031920 and alcohol consumption in EC and GCC. No association was observed between CYP1A1 and CYP2E1. The glutathione S-transferase mu 1 (GSTM1) null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The CYP1A1 rs4646903 and CYP2E1 rs2031920 polymorphisms were risk factors of GCC or EC, and the GSTM1 null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.

Association of genotypes of rs671 withinALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high- and low-incidence areas.

OBJECTIVE: : This study aimed to determine if gastric cardia adenocarcinoma (GCA) risk was associated with the lys (A or *2) allele at the rs671 (glu504lys) polymorphism within the aldehyde dehydrogenase 2 (ALDH2) gene in a Chinese Han population. We also aimed to investigateALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma (ESCC). METHODS: : We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and low-incidence areas for both GCA and ESCC in China. TaqMan allele discrimination assay was used to genotype the rs671 polymorphism.χ2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA, and multivariate ordinal logistic regression was used to analyzeALDH2 genotypic distributions among different groups. RESULTS: : Compared withALDH2*1/*1 homozygotes,ALDH2*1/*2 andALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population (P>0.05). Interestingly, the ratio of homozygous or heterozygousALDH2 *2 carriers in high-incidence areas for both GCA and ESCC was lower than that in low-incidence areas (P<0.001). CONCLUSIONS: : Genotypes of rs671 atALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, theALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.