The Relationship Between The Genetic Polymorphism Of PLCE1 And C20orf54 And Susceptibility To Gastric Carditis

1. BackgroundGastric cardia adenocarcinoma (GCA) has the significant epidemiological features with esophageal cancer (EC) in terms of concurrent geographic distribution, especially, the regions at junction of Henan, Hebei, and Shanxi provinces in northern China, which are the highest incidence and mortality areas worldwide. The study for the tissue occurrence model of GCA, especially precancerous lesions, reported little currently. In recent years, the incidence trend of esophageal junction adenocarcinoma was significantly increased, which is the fastest growing one of all human malignant tumors in Western countries, and the junction of intestinal metaplasia and dysplasia is considered as an important Precancerous lesions. However, with the obvious difference of Chinese people, the junction of esophageal adenocarcinoma of Western countries is mainly the lower esophageal cancer and GCA, but for the Chinese people is almost GCA. Recent studies suggest that gastric carditis may be the important precancerous condition of GCA, but the study on molecular mechanism of gastric carditis is little. We first identified 2 novel susceptibility loci for EC and GCA: rs2274223 on 10q23 and rs13042395 on 20p13 performing a Genome-wide Association Study (GWAS). One gene at each locus was implicated:PLCE1 at 10q23 and C20orf54 at 20p13, PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 has been identified as a riboflavin transporter and plays an important role in the intestinal absorption of riboflavin.The susceptibility to gastric carditis on the two genes has not been reported, in this study, to evaluate the relationship between gastric carditis and GCA, the detection rates of endoscopic mild and severe gastric carditis and GCA were compared between the high- and low-incidence areas for GCA. Then compared the genotypes of rs2274223 and rs13042395 among the normal population, severe gastric carditis and GCA, further to understand the relationship of high-risk susceptibility loci on rs2274223 and rs13042395 for gastric carditis, and establish the basis of molecular markers for early warning and diagnosis of high-risk groups. 2. Materials and methods2.1 Study populationThe first part:for the 50,661 subjects,8,514 patients were from out-patient clinic (OPD) of gastroscopy from Hospital of Cixian, Hebei, Tumor Hospital of Anyang, Henan and Peace Hospital of Changzhi, shanxi of high-incidence area for GCA and 42,147 patients from OPD of gastroscopy from People's Hospital of Puyang, Henan of low incidence area. The second part:the subjects of control (n=1,316), gastric carditis (n=258) and GCA (n=1,192), which were from the same hospitals with the first part.2.2 Epidemiologic InvestigationThe questionnaire and endoscopic examination were performed on all subjects from the high- and low-incidence areas.2.3 Genotypes MethodThe genotypes (AA/AG/GG) of rs2274223 and (CC/CT/TT) of C20orf54 are derived from the Sequenom MassArray System.2.4 Statistical AnalysisWe conducted all analyses with the use of SPSS software (version 17.0) of the logistic regression analysis and Chi-square test, Significance levelα=0.05, using odds ratio (OR) and 95% confidence interval (95% CI) to evaluate relative risk.3. Results3.1 The detecting rate of mild gastric carditis in high-incidence area (1.49%, 127/8,514) was significantly lower than that in the low-incidence area (3.50%, 1,475/42,147) (P<0.01), however, the detecting rate of severe gastric carditis in the high-incidence area (1.41%,120/8,514) was almost 4 folds higher than that in low-incidence areas (0.32%,133/42,147) (P<0.01). The detecting rate of GCA in high-incidence area (5.54%,472/8,514) was significantly higher than the low-incidence area (2.62%,1105/42,147) (P<0.01).3.2 The detecting rates of gastric carditis and GCA in male between the high- and low-incidence areas for GCA were higher than in female (P<0.01), and with the increasing age, the trend of the detecting rates of gastric carditis and GCA are growing.3.3 The cases and controls were up to standard of Hardy-Weinberg equilibrium, which could be on behalf of the population.3.4 The genotype of rs227422 locus between the normal and gastric carditis was no significant difference (P=0.212), but the genotype between gastric carditis and GCA was significant difference (P=0.001).3.5 The genotype of rs13042395 locus between the normal and gastric carditis was significant difference (P=0.019), and the genotype between gastric carditis and GCA was no significant difference (P=0.337).3.6 Multivariate logistic regression analysis showed that:male and high incidences of GCA are high-risk factors.3.7 Adjusting for the sex, age, high- and low-incidence areas and family history, the genotype of rs227422 between the normal and gastric carditis was no significant difference (P=0.361), but the genotype between gastric carditis and GCA was significant difference (P=0.001).3.8 Adjusting for the sex, age, high- and low-incidence areas and family history, the genotype of rs13042395 between the normal and gastric carditis was significant difference (P=0.013), but the genotype between gastric carditis and GCA was no significant difference (P=0.403).4. Conclusions1. The dramatic higher detection rate for severe gastric carditis in the high-incidence area, which is consistent with the prevalence pattern for GCA, suggests that severe gastric carditis may have an important association with the occurrence of GCA, which needs further follow-up to be demonstrated.2. rs13042395 locus mutation has an effect on the occurrence of gastric carditis.