title: Prediction of the risk for gastric cancer using candidate methylation markers in the non-neoplastic gastric mucosae.
abstract: Aberrant DNA methylation is frequently found during gastric carcinogenesis. Recently, we identified potential methylation markers important for Helicobacter pylori-induced gastric carcinogenesis using an Illumina methylation chip assay. In this study, we evaluated the candidate genes as markers for gastric cancer (GC) in a large Korean population. DNA methylation of PTPN6, MOS, DCC, CRK, and VAV1 was evaluated in non-neoplastic gastric specimens using quantitative methylation-specific PCR in patients with GC (n = 207) and their age- and gender-matched controls (n = 207). Methylation levels in 125 GC samples were also compared. H. pylori infection status was categorized as negative, active, or past infection according to the results of endoscopy-based tests (CLOtest, histology, and culture), H. pylori serology, and serum pepsinogen test. In the controls, active H. pylori infection increased methylation levels in DCC, CRK, MOS, and VAV1 but decreased methylation levels in PTPN6 (all p < 0.05); the methylation levels in MOS remained increased in patients with past H. pylori infection compared to H. pylori-negative subjects (p < 0.001). Methylation levels in MOS in non-neoplastic gastric mucosae increased in the presence of GC, regardless of H. pylori infection status (p < 0.01). Methylation levels in all genes but DCC decreased significantly in GC specimens compared to neoplastic gastric mucosae (p < 0.01); however, methylation levels in GC tissues were not correlated with those in their background gastric mucosae. Hypomethylation of MOS in GC tissues was associated with tumour invasion, nodal metastasis, and undifferentiated histology (p < 0.05). To summarize, among the candidate genes, DNA methylation of MOS may reflect the duration of H. pylori exposure and may be a marker for the development of GC.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
mesh_terms: D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D016258:Genes, mos / Q000235:genetics; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D011237:Predictive Value of Tests; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology / Q000473:pathology*