| Objective: Esophageal cancer is one of common malignant tumors in China, the morbidity and mortality is ranking first in the world which is a serious threat to human life and health. Cixian and Shexian of Hebei Province located in the southern foot of Taihang Mountains, is the high incidence of primary esophageal cancer, in recent years we have found that the incidence of cardia cancer in this region were at a high level, there was a a common phenomenon of high incidence of esophageal and gastric cardia. Studies have shown that nutritional deficiencies, poor eating habits of life, as well as smoking, drinking and environmental factors were the factors of incidence of esophageal and cardiac risk, but exposed to the same environmental factors affected the incidence in all groups, suggesting that the existence of differences in genetic susceptibility between individuals, and this difference in susceptibility played an important role to tumor development, Therefore, to explore with esophageal cancer and cardiac-related genetic characteristics of multiple genes is necessary.BCL-2 gene is an oncogene, through confronting pro-apoptotic factor in early cell differentiation to extend cell survival so that damaged DNA cells are immortalized, thus increasing the chance of other gene mutations, and cancer early formation. The topic detected the gene polymorphism of apoptosis-suppressing gene BCL-2 promoter region and transcription start site -938 (C/A) ,to explore the relevance of which with the morbidity risk of the people of southern foot of Taihang Mountain with high incidence of esophageal cancer (Esophageal carcinoma, EC), cardiac (Gastric cardiac adenocarcinoma, GCA) and precancerous lesions (precancerous lesions). Methods: A population-based case - control study of 145 cases from the high incidence of esophageal squamous cell carcinoma (Esophagealsquamous carcinoma, EC), 165 cases of esophageal precancerous lesions, 169 cases of gastric cardia adenocarcinoma (Gastric cardiac adenocarcinoma, GCA) , 92 cases of cardiac precancerous lesions and 195 normal controls, research. All specimens were taken from endoscopic biopsy of the esophagus, gastric mucosa, while recording personal history, smoking and drinking status, family history and other information, And to remove the history of their own other malignancies. The tissure DNA was extracted using UNIQ-10 column animal genomic DNA Extraction Kit, adopting a method carried out using polymerase chain reaction-restriction fragment length polymorphism analysis (polymerase chain reaction-restriction fragment length polymorphasm, PCR-RFLP) which used to detect BCL-2 genotype, the optional display different genotypes to sequence the DNA samples, sequenced. Statistical analysis of data used SPSS13.0 Package (SPSS Company, Chicago, Illinois, USA), P<0.05 considered statistically significant, done the distribution of Hardy-Weinberg equilibrium analysis Of BCL-2 genotype in the normal control group. Case group and control group was used to compare the genotype distribution of line×list of chi-square test. To non-conditional Logistic regression method by gender, age, smoking, drinking status and family history of upper digestive tract cancer, correction of relative risk odds ratio (odds ratio, OR) and 95% confidence interval (confidence interval, CI).Results:1 The study of general characteristics:1.1 Esophageal precancerous lesions in patients with esophageal squamous cell carcinoma group and the group the proportion of smokers (38.2% and 46.2%) compared with the control group (34.4%), esophageal cancer were significantly different (χ~2 value of 4.889, P values were 0.027), by age, gender, family history of corrected OR = 1.489 (95% CI = 0.838-2.646).1.2 Cardia precancerous lesions of gastric cardia adenocarcinoma group and the proportion of patients with smoking group (respectively 42.4% and 52.5%) was significantly higher than those in healthy controls (34.4%) (χ2 = 2.223, and 18.446, P = 0.136 and 0.000) Thus, Smoking significantly increase the incidence of cardiac risk, by sex, age adjusted OR = 3.158 (95% CI = 1.624-6.140).1.3 Esophageal cancer, precancerous lesions and cardiac carcinoma, precancerous lesions of the proportion of drinkers (31.7%, 18.2% and 30.8%, 30.4%) and the control group (23.1%) compared with no significant difference (P>0.05);more than the proportion of positive family history of the four groups (35.2%, 40.0%, 33.1%, 43.5%) and the control group (33.8%) compared with no statistical significance.2 The relationship between the BCL-2SNP with esophageal squamous cell carcinoma, gastric cardia adenocarcinoma and precancerous lesions2.1 In control group, pre-esophageal lesions and esophageal cancer in the group BCL-2 polymorphic loci of the genotype distributions were consistent with Hardy-Weinberg equilibrium (P values > 0.05), three groups of BCL-2-938 AA, CA, CC genotype frequencies were 19.0%, 47.2%, 33.8%; 11.5%, 41.8%, 46.7%; 11.0%, 40.7%, 48.3%, CC genotype in esophageal precancerous lesions, esophageal cancer group and healthy controls There was a significant difference (P values <0.05), compared with the AA genotype carrying CC genotype can significantly increase the incidence of esophageal cancer and precancerous lesion risk, by sex, age, smoking, family history of corrected OR values were 2.418 (95% CI = 1.245-4.696) and 2.386 (95% CI = 1.195-4.764).2.2 The healthy control group, cardiac precancerous lesion group and the cardiac group of BCL-2 polymorphic loci of the genotype distributions were consistent with Hardy-Weinberg equilibrium (P> 0.05), three groups of BCL-2-938 AA, CA, CC genotype frequencies were 19.0%, 47.2%, 33.8%; 8.7%, 42.5%, 47.8% and 10.7%, 40.8%, 48.5%. BCL-2 CC genotype frequency in cardiac precancerous lesion group, cardia cancer group were significantly higher than in healthy controls, with statistical significance (P values <0.05), compared with the AA genotype, carrying CC gene significant increased in cardiac the incidence of cancer and the risk of precancerous lesions by sex, age, smoking, family history of corrected OR values were 2.564 (95% CI = 1.268-5.184) and 2.810 (95% CI = 1.179-6.639).3 stratified analysis3.1 According to the status of individual smoking stratified analysis found that, compared with the AA genotype, carrying CC genotype significantly increased smoking individuals the incidence of esophageal cancer and cardia cancer of the risk, by sex, age, family history, drinking corrected OR values were 3.176(95%CI=1.009-9.994)and 3.635(95%CI=1.226-10.777) .The BCL-2-938C / A SNPs does not affect the risk of the incidence of smoking history of esophageal precancerous lesions and cardia precancerous lesions.3.2 According to the status of individual drinking stratified analysis found that, compared with the AA genotype, carrying CC genotype significantly increased non-drinking individuals the incidence of esophageal cancer and precancerous lesions of the risk, by sex, age, family history, smoking Smoke corrected OR values were 2.641 (95% CI = 1.197-5.825) and 2.097 (95% CI = 1.012-4.344), and precancerous lesions in the cardia cancer group carrying CC genotype and AA-type can significantly increase non - The incidence of individual risk of alcohol, after correction by other factors, OR values were 2.379 (95% CI = 1.053-5.377) and 3.708 (95% CI = 1.278-10.760). The BCL-2-938C / A SNPs does not affect the risk of the incidence of drinking history of esophageal cancer-positive individuals, cardia cancer and precancerous lesions.3.3 According to stratified analysis whether a family history with upper digestive tract found that the AA genotype,compared with the BCL-2-938C/ASNP, carrying CC genotype-negative family history of UGIC significantly increased the individual esophageal cancer and precancerous lesions, the incidence of cardia cancer and the risk of precancerous lesions (P <0.05), by smoking, drinking, sex, age, after correction for OR values were 2.692 (95% CI = 1.162-6.232), 2.452 (95% CI = 1.078-5.573) and 2.632 (95% CI = 1.148-6.032), 4.240 (95% CI = 1. 419-12.671). In UGIC family history-positive group, three kinds of genotype frequency distribution was no statistical difference.3.4 Stratified by gender analysis found that, compared with the AA genotype, CC genotype men can increase the risk of gastric cardia adenocarcinoma and precancerous lesions at risk, by age, smoking, drinking status and family history of corrected OR values were 2.563 (95% CI = 1.003 ~ 6.551), 4.178 (95% CI = 1.098 ~ 15.889), but not found that BCL-2-938C/ A SNPs was related to the incidence of esophageal squamous cell carcinoma and its precancerous lesions.Conclusions:1. Smoking can significantly increase the high incidence of esophageal cancer group and the incidence of cardiac risk; compared with the AA genotype, BCL-2-938 CC genotype increase the incidence of the esophagus and cardiac risk, the risk of esophageal and cardia cancer incidence in the smoking positive group genotype has increased significantly.2. Compared with the AA genotype, BCL-2-938 CC genotype may be a significant increase in the incidence of cardiac risk of esophageal precancerous lesions and cardia precancerous lesions.3. BCL-2 gene polymorphism may be related to the risk of esophageal cancer and precancerous lesions associated morbidity of family history of non-drinking alcohol, negative upper digestive tract of individuals, namely, CC gene can be a significant increase in the incidence of the risk of the above-mentioned individuals.4. BCL-2 gene polymorphism may be related to the risk of cardia cancer and precancerous lesions associated morbidity of male, non-drinking, family history of upper digestive tract-negative individuals, namely, CC gene can be a significant increase in the incidence of the risk of the above-mentioned individuals.
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