The Relationship Study Of Polymorphism Within Gene With Some Clinical Features Of Esophageal Disease And Peptic Ulcer

Background And ObjectiveEsophageal cancer (EC) is the sixth common cause of cancer-related deaths in the world, significant differences in regional distribution of the epidemiological characteristics of its outstanding. The difference between high and low area incidence rate of 500 times. Lacking of early specific clinic symptoms, more than 85% of esophageal cancer patients are at middle and advanced stages when diagnosed at the first time. The five years survival rate for these patients is only 10%～15%, which is the primary reason for the high mortality rate of this disease. Esophageal carcinogenesis is a multistage progress, and esophageal epithelial cell hyper-proliferation is the early indicator for the subjects predisposed to esophageal cancer, morphologically manifested as basal cell hyperplasia (BCH), dysplasia (DYS) and carcinoma in situ (CIS), which could be considered as precancerous lesions for esophageal cancer. Esophageal diseases as the state of precancerous for esophageal cancer, which could be provide an available micro-environment.Helicobacter pylori (Hp) as the main pathogeny of Peptic ulcer (PU) has been confirmed. Many clinical studies suggested that Hp eradication could improve the symptoms, or even revealed a relief of PU after the cure of Hp infection. Several studies have shown that Hp eradication could provoke or worsen esophageal diseases, however, a few studies suggested that it may be a relief of reflux symptoms. Therefore, whether Hp infection is a protective or predisposing factor for the development of esophageal diseases remains controversial.However, esophageal precancerous lesions have potential of reversibility, eg., they may stay in the same stage for many years, or progress to more severe lesions, even return to normal. In that way, it is limited to explain this phenomenon what is the key mechanism to drive the mild precancerous lesions to the direction of cancer development in morphological level. Alterations in protein and genetic level may be one of the key mechanisms for the different outcome of the precancerous lesions with similar morphology. We have compared the SNPs with esophageal diseases, PU and patients with Hp infection by genome-wide association study (GWAS). To explore the relationship between the high risk locus and clinical phenotypes of esophageal diseases, PU and Hp infection. To elucidate the molecular mechanism for esophageal cancer pathogenesis and to provide a theoretical basis for early diagnosis, treatment and prevention of the disease.Materials And Methods1 MaterialsWe enrolled 11 013 patients which endoscopy were performed and they came form more than forty hospitals in Henan, Shanxi, Hebei province et al. from 2009 to 2010. The number of male was 5638 (51.2%), average age was 47.32±11.24, the median age of 52.5 years. And female was 5375 (48.8%), average age was 48.10±10.64, the median age of 52 years.2 MethodsAll patients recruited to the study gave their written, informed consent. Questionnaires were performed and recorded common conditions such as name, sex, age, height, weight, blood pressure, the habit of smoking and drinking and so on. All the collected clinical information was entered Excel sheet. The genotypes (AA/AC/CC) were derived from the Illumina 610-Quad Bead Chips and the Sequenom Mass Array System of our esophageal cancer genome-wide association study (GWAS).3 statistical analysisTheχ2 test was used for the statistical analysis with software SPSS 17.0. P values of less than 0.05 were considered to indicate statistical significance.Results1. The genotype and allelic frequency of rs6140125 polymorphism within C20orf54 gene were of significant relationship between esophageal disease and controls (χ2=67.06, P=2.74E-15, df=2;χ2=63.27, P=1.80E-15, df=1, OR=1.50,95% CI 1.36-1.66).2. The genotype (χ2=34.02, P=4.10E-8, df=2) and allelic frequency (χ2=32.47, P=1.21E-8, df=1, OR=1.49,95% CI 1.30-1.71) of rs6140125 polymorphism for C20orf54 gene were of significant relationship between peptic ulcer and controls.3. There were not significant relationship between esophageal disease and peptic ulcer of genotype and allelic frequency for rs6140125 polymorphism (χ2=0.43, P=0.81, df=2;χ2=0.02, P=0.89, df=1, OR=1.01,95% CI 0.87-1.17).4. There were not significant relationship between esophageal disease and peptic ulcer of genotype frequency for rs6140125 polymorphism within C20orf54 gene in gender (χ2=0.24, P=0.89, df=2;χ2=0.26, P=0.88, df=2).5. There were not significant relationship between esophageal disease and peptic ulcer of genotype frequency for rs6140125 polymorphism in high-/low incidence areas (χ2=2.53, P=0.28, df=2;χ2=3.61, P=0.17, df=2).6. There were not significant relationship between esophageal disease and peptic ulcer of genotype frequency for rs6140125 polymorphism in the family history (χ2=0.43, P=0.81, df=2;χ2=0.73, P=0.70, df=2).7. There were not statistical significant between esophageal disease and H. pylori infection of genotype and allelic frequency for rs6140125 polymorphism (χ2=3.38, P=0.18, df=2;χ2=3.38, P=0.07, df=1, OR=1.11, 95% CI 0.99-1.23).Conclusions1. The rs6140125 polymorphism within C20orf54 gene is associated with the susceptibility of esophageal disease and peptic ulcer.2. The results suggested that there is no obvious correlation of the incidence between esophageal disease and peptic ulcer, and also no discrepancy in gender, high-/low incidence areas and family history.3. H. pylori infection might lead to an increased risk of esophageal disease.