Correlated Analysis Of Esophageal And Gastric Cardiac Cancer With Family History

1. BACKGROUND AND OBJECTSEsophageal cancer (EC) is one of the six most common malignant tumors worldwide and Taihang mountain areas at the junction of Henan, Hebei and Shanxi provinces has been well documented as the highest incidence areas for esophageal cancer in the world and the incidence of EC decreases from the areas centre to the edge. The remarkable geographical distribution is the striking characteristic for EC. The ratio for EC incidence between the high- and low-risk areas could be as high as 500:1. Gastric cardia adenocarcinoma (GCA) is one of the most common malignant digestive diseases in northern China. A remarkable epidemiological characteristic for GCA is the occurring together with esophageal cancer (EC) in the same high-incidence area. Another remarkable epidemiological characteristic for EC/GCA is the dramatic familial aggregation. Recent studies by us found that the dramatic familial aggregation in Linzhou is obviously higher than in Henan areas without Linzhou and in other provinces, our another epidemiological investigation found that after 100 years, the prevalence of EC/GCA and the prevalence of esophageal precancerous lesions in the migrated subjects is similar with Linzhou subjects.The remarkable geographical distribution and the dramatic familial aggregation, especially migrant epidemiology suggests that both enviromental and genetic factors may play important roles in EC/GCA carcinogenesis. At present, however, there are little understanding about the molecular mechanism and proportion of enveriment and heredity on EC/GCA carcinogenesis, especially the researches on the GCA genetic predisposition (family history).At present, key candidate genes involved in EC/GCA have not been identified, one of primary reasons is because of the difficultyes in pedigree data collection. Through the mass survey and follow-up studies in high incidence area in Henan, we have demonstreated the high frequency of positive EC/GCA family history, and EC/GCA familial aggregation in these area named as "high risk family for EC/GCA" (°≥2 EC/GCA patients within generations), The unique for these population is that all the people are living in the same countyside for several generations with similar environment and genetic background. Furthermore, this population has many family memebers. All this features are much desirable to elucidate key genes related with EC/GCA (candidate susceptibility genes). Obviously, it is crucial foundation to collect and sort clinical and genetic background data, and to establish EC/GCA core pedigree to elucidate. Just based on the above mentioned studies, the present study was undertaken to establish core pedigree and to analyze the risk factors related with EC/GCA by interviewing with family members, collecting clinical and histopathological data,Thus, the present study was undertaken to analyze large scale of EC/GCA (family history) samples and EC/GCA (non-family history) samples in An Yang to determine the characteristics of the EC/GCA genetic predisposition and the proportion of envirment and hereditay on EC/GCA carcinogenesis. Based on the analysis for EC and GCA predisposition between EC/GCA with and without family history and to furthar elucidate the hereditary susceptibility of EC/GCA and to provide important clues and information in identifying the biomarkers for high-risk subject screening and early detection in EC/GCA. 2. MATERIALS AND METHODS2.1 Analysis of EC/GCA genetic predisposition (family history)2.1.1 Subjects2000 patients with EC/GCA were included in this study. Of these patients,1000 were with EC (male:585, female:415), with a mean age of 58±9 years; 1000 were with GCA (male:543, female:457), with a mean age of 54±7 years. All the EC/GCA patients were confirmed as primary SCC and GCA by histopathology. All clinical information for 2000 patients with EC/GCA was from hospitals in An Yang and Lin Zhou.2.1.2 The criteria for EC/GCA with and without family historyEC and GCA patients with tumor family history (EC FH+and GCA FH+) means the families with≥2 EC/GCA patients within continuous three generations.EC and GCA patients without tumor family history (EC FH-and GCA FH-) means the families with≤1 EC/GCA patients within continuous three generations. And at the same time, no other tumors recorded.2.1.3 Epidemiological investigationThe epidemiologic survey questionnaire was used and EC/GCA patients or their family members were interviewed at the hospitals by the investigators, including name, age, gender, family history, family personnel construction, dietary habits and mental factors, upper gastrointestinal tract disease, drug history, and so on. On another hand, the review of the medical records were done to collect all clinical information for EC/GCA patients in these hospitals. All the data of investigation were dealed using professional software.2.1.4 Analysis on genetic epidemiology dataChi-square test and risk estimate(odds ratio, OR) were used to evaluate the statistical significance. A p-value less than O.05 was considered to be statistically significant. All statistical analyses were performed using the SPSS 13.0 software.3. RESULTS EC FH+in male (59.2%,296/500) was not higher than EC FH-(57.8%,289/500), P>0.05. Female EC FH+(40.8%,204/500) was lower than EC FH-(42.2%, 211/500), P>0.05. Comparing with EC FH+(ageâ†'40â†'50â†'60â†'70) with EC FH-,there was no significance between them (4.2%,21/500; 38.4%,192/500; 44%,220/500; 12.8%,64/500; vs 6%,30/500; 34.6%,173/500; 44.4%,222/500; 14%,70/500), P>0.05。GCA FH+ in male (54.8%,274/500) was not higher than GCA FH-(43.6%, 2=18/500), P>0.05. Female GCA FH+ (45.2%,226/500) was lower than GCA FH-(56.4%,282/500), P>0.05. Comparing with GCA FH+(ageâ†'40â†'50â†'60â†'70) with GCA FH-,there was no significance between them (3.2%,16/500; 34.2%,171/500; 45%,225/500; 11.9%,59/500; vs 5%,25/500; 35.9%,179/500; 41.5%,207/500; 16%,80/500), P>0.05。The relalionships of the factors were synthetical analyzed in the study, using the multivariateLogistic regression analysis.The results showed that advnced stage EC (OR=1.19,95% CI:0.53-2.69),poor differentiation EC(OR=3.695, OR 95% CI: 1.231-11.09),midpiece EC(OR=1.725, OR 95% CI:1.120-2.656),IV stage(0R=1.548, OR 95% CI:1.138-2.105). EC FH+ were responsible for the higher risk for EC than EC FH-. AT the same time, the results showed intermediate stage GCA(OR= 1.19,95% CI:0.53-2.69), moderately differentiated GCA (OR =3.695, OR 95% CI:1.231-11.09), juncture GCA (OR=1.725, OR 95% CI: 1.120-2.656),â…¢stage(0R=1.548, OR 95% CI:1.138-2.105). GCA FH+ were responsible for the higher risk for GCA than GCA FH-4. CONCLUSIONS4.1 Differences in EC/GCA genetic predisposition(family history)risk by gender and family oncologic histories imply that familial predisposition to EC/GCA may have a compound genetic and/or environmental correlation in different families. Familial predisposition to EC/GCA may be related to compound genetic and/or environmental etiologies, but genetic etiology may be more important by far.4.2 Compared to non family history of EC/GCA, people with EC/GCA family history may have the higher risk with the carcinogenesis and canceration.