1. Prostate Stem Cell Antigen Gene Polymorphism Is Associated with H. pylori -related Promoter DNA Methylation in Nonneoplastic Gastric Epithelium.
- Author
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Tahara T, Tahara S, Horiguchi N, Kato T, Shinkai Y, Okubo M, Terada T, Yoshida D, Funasaka K, Nagasaka M, Nakagawa Y, Kurahashi H, Shibata T, Tsukamoto T, and Ohmiya N
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Transformation, Neoplastic genetics, Cohort Studies, CpG Islands, Female, GPI-Linked Proteins genetics, Gastric Mucosa microbiology, Gastric Mucosa pathology, Gastritis genetics, Gastritis microbiology, Gastritis pathology, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Helicobacter Infections pathology, Humans, Male, Middle Aged, Mucin-1 genetics, Polymorphism, Single Nucleotide, Stomach Neoplasms genetics, Stomach Neoplasms microbiology, Antigens, Neoplasm genetics, DNA Methylation genetics, Gastric Mucosa metabolism, Helicobacter Infections genetics, Helicobacter pylori physiology, Neoplasm Proteins genetics, Promoter Regions, Genetic genetics
- Abstract
Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen ( PSCA ), and the other was a polymorphism (rs4072037) in mucin 1 ( MUC1 ). DNA methylation is associated with gastric cancer and Helicobacter pylori ( H. pylori )-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori , a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori- -related promoter CGI methylation in the nonneoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection ( IGF2, MYOD1 , and SLC16A12 ). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori -positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95% CI (confidence interval), 1.06-5.29; P = 0.035] and T/T genotypes (OR, 3.2; 95% CI, 1.41-7.25; P = 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori -related promoter DNA methylation in the gastric mucosa. Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction., (©2019 American Association for Cancer Research.)
- Published
- 2019
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