Association Research Between Environmental Risk Factors, Polymorphism Of NQO1 And Susceptibility To Esophageal Cancer

ObjectiveTo investigate the risk factors of esophageal cancer,the association between geneticpolymorphisms of NQO1 and susceptibility to esophageal cancer, and thegene-environmental interaction in etiology of esophageal cancer, a hospital-basedcase-control study was conducted in Anxi of Fujian Province. This will be the foundationfor further revealing the cause of esophageal cancer and preventing the carcinoma.Materials & methodsUsing 1:2 matched case-control study, we have identified 185 esophageal cancerpatients with endoscopy and pathology diagnosis from Anxi hospital during the periodsfrom November, 2003 to August, 2004. Each had no history of radiation therapy orchemotherapy. A total of 370 controls without history of malignant tumor or digestivesystem diseases were selected during the same period as cases and matched to each caseby gender, age, nationality and inhabited areas.Epidemiological data of cases and controls were firsthand collected by traininginterviewers according to the constructed questionnaire. About 5ml whole blood of casesand controls was collected. After separating the serum, we extracted genomic DNA fromclotted blood using a simple salting out protocol. The HinfⅠpolymorphism of NQO1 wasdetected by PCR-RFLP.Conditional logistic regression was used to analyze the interaction between the geneand environmental factors, and to calculate odds ratios and 95% confidence intervals forpossible risk/protective factors. All the calculations and statistics were performed with thecomputer program, SPSS Version 12.0.Results 1. Multivariate conditional Logistic regression analysis showed tobacco smokingamount (OR=2.681, 95%CI:1.297-5.544), consumption of excessive salt (OR=4.463,95%CI:1.370-14.545), sweet potato (OR=4.891, 95%CI:1.659-14.415), the family historyof esophageal cancer(OR=4.675, 95%CI:1.611-13.571), tendency to self-restraint(OR=1.507, 95%CI:1.131-2.007), over-hot tea drinking (OR=5.749, 95%CI: 1.526-21.653)were the risk factors of esophageal cancer; while conservation of food inrefrigerator(OR=0.136, 95%CI:0.048-0.388) and dry place (OR=0.093, 95%CI:0.041-0.211), regular diet (OR=0.441, 95%CI:0.302-0.643), fresh vegetable (OR=0.328,95%CI:0.185-0.580) and cereal(OR=0.583, 95%CI:0.366-0.928) , allium vegetables(OR=0.397, 95%CI:0.208-0.758)were the protective factors of esophageal cancer. 2. The frequencies of NQO1 609CC,CT and TT genotype were 27.1%,43.7% and29.2% in esophageal cancer and 32.8%,50.0% and 17.2% in controls, respectively (χ2=3.966, P=0.046) .The frequency of the NQO1 609T allele was 51.0% for cases and42.0% for controls, P=0.044. NQO1 609TT genotype had a significant increased risk ofesophageal cancer (adjusted OR=2.019, 95%CI:1.112～3.663) compared to 609CC or609CT genotype. 3. As for the interaction between gene and related exposure factors , significantgene-environment interaction was observed with NQO1 609TT genotype and tobaccosmoking amount(OR=7.706, 95%CI: 1.195～49.694), allium vegetables (OR=9.849, 95%CI: 3.733～25.985) which appear to act in a super multiplicative way. There was alsoobvious relationship between the family history of esophageal cancer and consumption ofexcessive salt(OR=5.760, 95%CI: 2.200～15.080), allium vegetables (OR=7.373, 95%CI:3.082～17.637). No interaction between tea drinking and NQO1 gene, the family historyof esophageal cancer was found, but interaction between over-hot tea drinking andNQO1 gene(OR=4.847, 95 % CI:1.817 ～12.929), the family history of esophagealcancer(OR=8.396, 95%CI: 2.917～24.171) was found that contribute to esophagealcancer in this study. Furthermore, highly interaction was found in tobacco smoking withalcohol drinking(OR=2.587, 95 % CI: 1.145 ～5.844),and this means that a supermultiplicative type of interaction occurs.Conclusion Results in the present study suggested that tobacco smoking amount, consumption ofexcessive salt, sweet potato, the family history of esophageal cancer, over-hot tea drinking,tendency to self-restraint and so on, were the risk factors for esophageal cancer; whileconservation of food in refrigerator and dry place, regular diet, fresh vegetable and cereal ,allium vegetables were regarded as protective factors to esophageal cancer. NQO1 609TTgenotype is positively associated with the risk of esophageal cancer. There was acoordinated effect between NQO1 609TT genotype and habits of tobacco smokingamount, allium vegetables and over-hot tea drinking in the development of esophagealcancer; Moreover, the family history of esophageal cancer had shown significantinteraction with allium vegetables, consumption of excessive salt, over-hot tea drinking inthe occurrence of esophageal cancer. Environmental factors, heredity and genes play an important role in the progress ofesophageal cancer in the high incidence area of Fujian province, and there are somedefinite interactions between them. Therefore, the people settled in high incident areashould alter their behavior habits, adjust meal structure and have good mentality in orderto prevent esophageal cancer effectively; Moreover, who bearing family history ofesophageal cancer and exposing risk factors were the higher risk population of esophagealcancer, and more attentions should be paid to them in the carcinoma control program. Theassociation between NQO1609TT genotype and susceptibility to esophageal cancer needmany studies to be testified, then, NQO1609TT genotype would be a target for screeningof esophageal cancer.