| [Objectives]1. Searching for the risk factors and etiological clues of gastric cardia cancer.2. To study the association between genetic polymorphisms of CYP2E1 and/or GSTM1, GSTTl and susceptibility to gastric cardia/non-cardia cancer, and to investigate the interaction of genetic and environmental factors in etiology of gastric cardia/non-cardia cancer.[Subjects and methods]1. Subjects The cardia cancer group (n=159) consists of all inpatients who were diagnosed with primary cardia cancer and were identified between Apr and Nov in 2001 from five hospitals: First-accessory hospital of Fujian Medical University, Xiehe hospital affiliated Fujian Medical University, Fujian provincial hospital, Tumor hospital of Fujian province and Zong hospital of Fuzhou. Base on a rolling-match method of recruitment and the cardia cancer group as reference, frequently-match non-cardia gastric caner (n=154) and controls (n=192) by gender and age (±3y) were continuously recruited.2. Investigate items and methods A structured questionnaire was administered face to face to all subjects, which contained questions on soci-demographic characteristics, personal medical history, family cancer history, life-long smoking habits, tea consummation, alcohol drinking, uses of refrigerator to store foods, and 15 main food items including fruit, raw vegetables, fish juice, salted food and other foods in Fujian province.3. Materials and methods of experiment About 2 ml of whole blood was collected. After collecting the serum, we isolated genomic DNA from the coagulated blood using DNAzol reagent. The PstI polymorphic site ofCYP2E1 was investigated by PCR-RFLP. GSTM1 and GSTT1 genotypes were determined by multiplexed PCR using three sets of primers with β-globin as an internal control. [Results]1. Risk factors The risks positively associated among those who smokes(OR=1.98, 95%CI: 1.12-3.51), whose first grade relativities suffered from cancer(OR=3.16, 95%CI: 1.63-6.11), those who diet irregularly (OR=2.22, 95%CI: 1.26-3.90), who drink well water daily(OR=2.62, 95%CI: 1.59-4.33) and those who had suffered from gastric diseases(OR=2.11, 95%CI: 1.33-3.35). An inverse associations were observed with the consumption of raw fruit(OR=0.15, 95%CI: 0.07-0.36), vegetables(OR=0.39, 95%CI: 0.16-0.97) and conservation of food in refrigerator(OR=0.50, 95%CI: 0.29-0.87). The risks were also elevated among those who consumed more salted meats(OR=4.96, 95%CI: 0.99-24.95), salted fish(OR=1.92, 95%CI: 0.86-4.20) and wine(OR=3.09, 95%CI: 0.68-14.03), but the odds ratios do not reach a significant level.2. Prevalence of CYP2E1, GSTM1 and GSTT1 genotypes The prevalence of CYP2E1 cl/cl, cl/c2 and c2/c2 genotypes in controls were 40.1%, 57.3% and 2.6%, respectively. While in cardia cancer cases those were 60.4%, 35.8% and 3.8%, respectively. And in the non-cardia gastric cancer cases those were 61.0%, 36.4% and 2.6%, respectively. The prevalence of GSTM1 null genotype was 44.8% in controls, 48.4% in cardia cancer cases and 44.2% in non-cardia gastric cancer cases. The prevalence of GSTT1 null genotype was 59.9% in controls, 58.49% in cardia cancer cases and 56.5% in non-cardia gastric cancer cases.3. Risk genotypes The adjusted ORs of CYP2E1 cl/cl genotype for cardia and non-cardia gastric cancer were 2.37(1.52-3.70) and 2.52(1.61-3.94), respectively. No significant difference between GSTM1 genotypes and GSTT1 genotypes were observed between cases and controls.4. Gene-environment and gene-gene interaction analyses we observed a super-additive risk-difference modification by smoking status in assessing the risks of CYP2E1 genotypes on gastric cancer. No obvious interaction was observed between CYP2E1, GSTM1 and GSTT1 genotypes on the risk ofgastric cancer.5. Cardia Vs non-cardia gastric cancers We compared the CYP2E1, GSTM1 and GSTT1 genotypes between th... |
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