| Objective:Esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GA)is China's two most common malignant tumor.ESCC and GA which occurred simultaneously in the same patient is called the esophageal/gastric double primary carcinoma (EGDC).The pathologic category of the cancer tissues in EDGC are different.Because of the same internal and external environmental factor in EGDC,it is an ideal model of screening differences in protein and gene changes in esophageal cancer and gastric cancer.It provides a good research material for studying the molecular mechanisms,susceptibility and cancer risk factors of ESCC and GA.Now there are two genetic mechanisms in the occurrence of the cancer.One is genetic mechanism which is changes in DNA sequences,such as gene mutation,loss of heterozygosity and microsatellite instability.The other is the epigenetic mechanism,which is DNA epigenetic modification and methylation is the main form.Methylation can make gene inactive and the expression of protein abnormal,so it can lead to the occurrence and the development of the cancer.The occurrence of esophageal cancer and gastric cancer is related to abnormal methylation of multiple genes.Studies have shown that,CDH1 gene as an important tumor suppressor gene,there is a high frequency of methylation in esophageal cancer and gastric cancer tissues.But there is no literature reporting the methylation of the CDH1 gene in EGDC.Through comparatively analysising the variation of methylation in CDH1 gene promoter CpG island and its relationship with cancer risk factors between the cancer tissues in EDGC from the same patient and in esophageal and gastric cancer,we want to explore the relationship between the CDH1 gene methylation and the carcinogenesis of esophageal carcinoma,gastric adenocarcinoma and EGDC.And we also want to know whether the two tumors appearing in the same patient have similar molecular basis of cancer and cancer risk factors.Methods:Endoscopic tissues from 80 cases of tumor patients (31 cases of ESCC,31 cases of GA and 18 cases of EGDC) and 9 cases of normal persons were collected in the Fourth Hospital of Hebei Medical University.The tissues include cancer tissues(ESCC and GA),adjacent control tissues,and the normal esophageal and gastric tissues as normal control tissues.And their medical history,personal information and family hi story of upper gastrointestinal cancer(UGIC)were recorded.With the Wizard ? Genomic DNA Purification Kit (A1620),DNA was extracted.After DNA was modified to the methylation status by using CpGenome? DNA Modification Kit (S7820),the methylation status in CDH1 gene promoter CpG island were detected.All data were analysised by SPSS 13.0 statistical software.We compared the relationship of every index with the chi-square test,paired chi-square test and Fisher's exact test. Test level ofαequal to 0.05.Results:1 CDH1 gene methylation in the esophageal cancer,adjacent control tissues and normal control tissues were detected1.1 CDH1 gene methylation positive rates in esophageal cancer,adjacent control tissues and normal control tissues were 51.6%(16/31),22.6%(7/31) and 0%(0/9)respectively.Compared cancer with adjacent control tissues,there is significant difference(χ2=7.111,P=0.004);Compared cancer with normal controls tissues,there is significant difference(P=0.006);Compared adjacent control tissues with normal controls tissues,there is no significant difference(P=0.175).1.2 Compared CDH1 gene methylation in esophageal cancer with patient's sex,age,alcohol and tobacco history and family history of UGIC,there is no statistics significance(P all >0.05).2 CDH1 gene methylation in gastric cancer,adjacent control tissues and normal control tissues were detected 2.1 CDH1 gene methylation positive rates of gastric cancer,adjacent control tissues and normal control tissues were 61.3%(19/31),41.9%(13/31)and 0%(0/9) respectively.Cancer compared with adjacent control tissues,there is no significant difference(χ2=2.5,P=0.109);cancer compared with normal controls tissues,there is significant difference(P=0.001);adjacent control tissues compared with normal controls tissues,there is significant difference (P=0.019).2.2 Compared CDH1 gene methylation in gastric cancer with patient's sex,age,alcohol and tobacco history and family history of UGIC,there is no statistics significance(P all >0.05).3 CDH1 gene methylation in esophageal cancer in EGDC,adjacent control tissues and normal control tissues were detected3.1 CDH1 gene methylation positive rates of esophageal carcinoma in EGDC,adjacent control tissues and normal control tissues were 66.7%(12/18), 33.3%(6/18) and 0%(0/9) respectively.Cancer in EGDC compared with adjacent control tissues,there is significant difference(χ2=4.167,P=0.031); cancer in EGDC compared with normal controls tissues,there is significant difference(P=0.001);adjacent control tissues compared with normal controls tissues,there is no significant difference(P=0.071).3.2 Compared CDH1 gene methylation in esophageal cancer in EGDC with patient's sex,age,alcohol and tobacco history and family history of UGIC,there is no statistics significance(P all >0.05).4 CDH1 gene methylation in gastric cancer in EGDC,adjacent control tissues and normal control tissues were detected4.1 CDH1 gene methylation positive rates of gastric cancer in EGDC,adjacent control tissues and normal control tissues were 77.8%(14/18),44.4%(8/18) and 0% (0/9)respectively.Cancer in EGDC compared with adjacent control tissues,there is no significant difference (χ2=1.786,P=0.180);cancer in EGDC compared with normal controls tissues,there is significant difference (P=0.000);adjacent control tissues compared with normal controls tissues,there is significant difference(P=0.026). 4.2 Compared CDH1 gene methylation in gastric cancer in EGDC with patient's sex,age,alcohol and tobacco history and family history of UGIC,there is no statistics significance(P all >0.05).5 The comparison of CDH1 gene methylation beween esophageal cancer, gastric cancer and esophageal/gastric double primary carcinoma5.1 CDH1 gene methylation positive rates of esophageal cancer and esophageal cancer in EGDC were 51.6%(16/31) and 66.7%(12/18) respectively.There is no significant difference(χ2=1.054,P=0.305).5.2 CDH1 gene methylation positive rates of gastric cancer and gastric cancer in EGDC were 61.3%(19/31) and 77.8%(14/18) respectively.There is no significant difference(χ2=1.408,P=0.235).5.3 CDH1 gene methylation positive rates of esophageal cancer and gastric cancer were 51.6%(16/31) and 61.3%(19/31).There is no significant difference between them(χ2=0.590,P=0.442).5.4 In esophageal cancer and gastric cancer of EGDC,the expression of CDH1 gene methylation is coherent(P=0.005).The positive methylation rates in two tumor tissues in EGDC are 66.7% and 77.8%. There is no statistical difference between them (χ2=0.5,P=0.500).In 18 cases of EGDC,16 cases (88.9%) in two kinds of tumour tissues were found simultaneous changes in consistency of CDH1 gene methylation.12 cases (66.7%) in two kinds of tumour tissues were found simultaneous CDH1 gene methylation. Neither in ESCC nor in GA in EGDC was detected CDH1 gene methylation in 4 cases(22.2%).Conclusions:1.In single and double primary esophageal carcinoma,the methylation rate in CDH1 gene promoter CpG island was significantly higher.2.In single and double primary gastric carcinoma,the methylation rate in CDH1 gene promoter CpG island methylation was significantly higher.3.Methylation positive rate in CDH1 gene promoter CpG island appears high in adjacent control tissues from single and double primary gastric carcinoma.There is no significant difference between adjacent control tissues and cancer,but there is statistical difference between adjacent control tissues and normal control tissues.It suggests that The change of CDH1 gene in molecular level of methylation may be earlier than in tissular level of pathology.4.The methylation expression of CDH1 gene promoter CpG island in CDH1 gene promoter CpG island in squamous cell carcinoma and gastric adenocarcinoma in EGDC is coherent. There is no statistical difference in the methylation positive rate between them.This indicates esophageal squamous cell carcinoma and gastric adenocarcinoma in EGDC may have similar molecular change.5.There is no relationship between the methylation in CDH1 gene promoter CpG island in ESCC and GA both in single carcinoma and in EGDC and the patient's sex ,age, alcohol and tobacco history and family history of UGIC.It suggests that methylation is probably an independent factor.
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