The Genetic Molecular Mechanism And Relationship Between Surname And Esophageal Cancer

BackgroundEsophageal cancer (EC) is one of the six most prevalent gastrointestinal malignancies worldwide. This disease is so hidden, that once found,90% of patients are advanced esophageal cancer. At the same time, the diagnostic rate of early stage is low and the prognosis is poor. Currently, esophageal cancer remains one of the major diseases threatening human life. The incidence of EC shows great geographical variation. Its high prevalence and mortality is of particular importance in Northern China, especially in Henan, Hebei and Shanxi Taihang Mountain area. Recent studies suggest that interaction of environmental and genetic factor may be an important mechanism leading to esophageal cancer. Some scholars have suggested:if inbreeding and common ancestry contributed to the development of the disease, then those phenomena should be reflected in increasing frequency of some surnames among ancestors, identifying the ’hidden’ consanguinity, or ’following’ cancer-promoting genes on the Y-chromosome. The results imply that there are surnames representing a classic "risk" for cancer, but also those "protecting" from its development, which all underscores the importance of founder effect and genetic predisposition to the disease in a small, reproductively isolated population. All of the results become more evident and increasingly significant when analyzed in more distant ancestral. Man can transfer the surname from generation to generation through the Male-specific Y chromosome. Meanwhile the genetic information on the Y chromosome will transfer steadily. The link between surname and chromosomal provide an evidence on the study of genetic structure and phylogenetic relationship. Those are well known as surname Gene named by scientists. Chinese surnames of Han as a unique cultural and population genetic markers has been concerned about the domestic and foreign scholars. However, there were little reports about surname as a sign of population genetics and disease, especially relationships of cancer genetic. This study aims to analyze Chinese Han population distribution of surnames in patients with esophageal cancer, a better understanding of esophageal cancer in Chinese Han surnames relations and to further elucidate the molecular mechanism of tumor genetic Han Chinese surnames and provide new ideas.The genome-wide association study (GWAS), one of the high-throughput biochip techniques, has been well-recognized as a breakthough in identifying the susceptibility genes of complex diseases, including cancers. The relationship between EC and surnames is recognized by GWAS in the case-control study.2 Materials and methods2.1 Analysis of the relationship among surname, blood type and esophageal cancer2.1.1 PatientsAll the clinical and pathological information from the 101171 cases with ESCC were sandomly derived from the ESCC biobank in Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital of Zhengzhou University. All the patients were diagnosed from January 1973 to December 2014. Of the cases, including 64658 males with a mean diagnosed age of 59.3±9.8 and 36513 females with a mean diagnosed age of 59.46±8.70.2.1.2 Follow-upAll the data were collected from the large-scale follow-up and questionnaire survey on the patients for EC. The information were enrolled with 2007 excel.2.1.3 StatisticsAll the data were analyzed using SPSS21.0 software. Chi-square tests were applied to clinical pathological data. P<0.05 was considered as significant.2.2 GWAS2.2.1 PatientsA total of 2076 cases and controls from Chinese Han population were enrolled in the GWAS. The peripheral venous blood samples (3-5ml) were collected from each patient and control and stored at-20℃.2.2.1 MethodsGenomic DNA was extracted by standard procedures using Flexi Gene DNA kits (QIAGEN, Germany) and the concentration was measured accurately, and normalized to 50 ng/μl with 1.8-2.0 OD in study. In our study, genotyping was performed using Illumina Human 610-Quad BeadChips according to the Infinium.Samples call rates and SNPs rates, minor allele frequency (MAF), Hardy-Weinberg equilibrium rates (HWE) were calculated, respectively. Quality controlled data were analyzed and outputted with SNP & Variation Suite 8 (SVS 8) software. P value, odds ratio (OR) and 95% confidence interval (95%CI) were calculated with Cochran-Armitage trend test.3 Results3.1 The distribution of Han surnames of esophageal cancer patients3.1.1 The distribution of Han surnames of esophageal cancer patientsThere are 101171 esophageal cancer patients, including 963 surnames,803 surnames in male and 640 surnames in female.There are 8 surnames’s ratio more than 2% of the total population,5 surnames in male and 4 surnames in female.3.1.2 The distribution of Han surnames of esophageal cancer patients between<50 ages and ≥50 ages in male and female.There are little difference between<50 ages and>50 ages in male esophageal cancer of Han. The same results to female esophageal cancer of Han.3.1.3 The distribution of Han surnames of esophageal cancer patients in different areas.There are significantly differences in Henan, Hebei, Shandong, Shanxi and Anhui of esophageal cancer patients. (x2=32.743, P<0.001). There are little difference between Henan and Hebei esophageal cancer of Han. The opposite results were in different areas. (P<0.05)3.2 GWASDifferent surname have different SNPs, when P value≤10-6、P value≤10-7、and P value≤10-8,the number of SNPs are different.when P value<10-7,only 5 surnames have SNPs. The esophageal cancer of Chen have 15 SNPs on Bland B2 gene.The esophageal cancer people of Li have 6 SNPs on D gene. The esophageal cancer people of Li have 6 SNPs on D gene. The esophageal cancer people of Zhang have 1 SNPs on F gene. The esophageal cancer people of Yang have 4 SNPs on H gene. The esophageal cancer people of Guo have 5 SNPs on I gene.Conclusions4.1 There was little difference in different ages of male esophageal cancer of Han. The same results to female esophageal cancer of Han. There are little difference between Henan and Hebei esophageal cancer of Han.4.2 Every surname had own susceptibility genesaffect of esophageal cancer, different surnames had different susceptibility genesaffect of esophageal cancer.