MTHFR C677T And P53 Condon 72 Pro/Arg Polymorphisms And Susceptibilities To Cardia And Non-cardia Gastric Cancer

【Objective】To study the association between genetic polymorphisms of MTHFR C677T and P53 Condon 72 Pro/Arg and susceptibility to gastric cardia/non-cardia cancer, and to investigate the interactions of gene and environmental etiology of these cancers in Fujian population.【Subjects and methods】1.Design method A Hospital based case-control study using a common control group for two cancer sites was conducted in Fujian province .2.Subjects The cardia cancer cases(155)consisted of all patients who were diagnosed with primary cardia cancer(within one year)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 General Hospital of FuZhou. Based on a rolling-match method recruitment, non-cardia gastric cancer cases(154) and controls (188)were frenquently matched to cardia cancer group by gender and age(±3y).3.Investigate items and methods All subjects were interviewed in person using a structured questionnaire. The questionnaire included information on soci-demographic characteristics, personal medical history, family history of cancer, smoking habits, 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.4.Materials and methods of experiment About 2 ml of blood was collected from every subject. After colleting the serum, genomic DNA was isolated from the coagulated blood using DNAZol reagent. The MTHFR C677T polymorphism and P53 Condon 72 Pro/Arg polymorphism were investigated by PCR-RFLP.【Results】 1.Distribution of MTHFR and P53 genotypes The frequencies of CC,CT and TT( MTHFR) were 48.4%,46.4% and 5.2% among cardia cancer cases and 42.2%,50.0% and 7.8% among non-cardia gastric cancer cases, respectively. While in controls the frequencies of MTHFR were 51.6%,40.4% and 8.0% for CC,CT and TT, respectively. The frequencies of P53 condon 72 genotypes Pro/Pro,Pro/Arg and Arg/Arg were 11.6%,54.8% and 33.6% among cardia cancer cases, 18.8%,48.7% and 32.5% in non-cardia gastric cancers,and 21.3%,48.4% and 30.3% among controls, respectively. 2.Risk genotypes The adjusted OR and 95% CI for variated genotype(CT or TT) of MTHFR compared with the wild type homozygous (CC) genotype was 1.618(95%CI :1.006-2.601). The OR and 95% CI for P53 Pro/Arg or Arg/Arg genotype compared with Pro/Pro genotype was 2.142(95% CI :1.084-4.231) after adjusting for potential confounders. 3.Gene-environment interaction analyses There were interactions between MTHFR variated genotype and low intake of fresh fruits in cardia cancer group. While the interactions between variated genotype and low intake of pean products, fresh fruits were observed in non-cardia gastric cancer group.We also observed interactions between P53 Pro/Arg or Arg/Arg genotype and smoking,the duration of smoking (≥30 years),the mumber of cigarets consumed (≥20/day),irregular meals, no drinking tap water in cardia cancer group.【Conclutions】 1.There may be different risk factors and etiologies between cardia and non-cardia gastric cancer. 2.The interaction between MTHFR variated genotype and low level of folates intake increase the risk of cardia cancer. And the variated genotype of MTHFR is a risk factor for non-cardia gastric cancer. The interaction between variated genotype and low level of folates intake increase the risk of non-cardia gastric cancer . 3.The P53 Pro/Arg or Arg/Arg genotype is a risk factor of cardia cancer. The risk was increased by smoking, irregular meals, no drinking tap water. 4.No obvious interaction was observed between MTHFR C677T and P53 Condon 72 Pro/Arg genetypes on the risk of gastric cancer.