DNA Methylation Predicts Progression of Human Gastric Lesions

Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer. A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylo...

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Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2015-10, Vol.24 (10), p.1607-1613
Main Authors: Schneider, Barbara G, Mera, Robertino, Piazuelo, M Blanca, Bravo, Juan C, Zabaleta, Jovanny, Delgado, Alberto G, Bravo, Luis E, Wilson, Keith T, El-Rifai, Wael, Peek, Jr, Richard M, Correa, Pelayo
Format: Article
Language:English
Subjects:
Adenocarcinoma - diagnosis
Adenocarcinoma - genetics
Adenocarcinoma - prevention & control
Adult
Anti-Bacterial Agents - therapeutic use
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Chemoprevention - methods
Disease Progression
DNA Methylation
DNA, Neoplasm - genetics
Double-Blind Method
Endoscopy, Gastrointestinal
Female
Forecasting
Gastric Mucosa - metabolism
Gastric Mucosa - microbiology
Gastric Mucosa - pathology
Helicobacter Infections - complications
Helicobacter Infections - drug therapy
Helicobacter Infections - microbiology
Helicobacter pylori - isolation & purification
Humans
Male
Middle Aged
Polymerase Chain Reaction
Precancerous Conditions - genetics
Stomach Neoplasms - diagnosis
Stomach Neoplasms - genetics
Stomach Neoplasms - prevention & control
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Summary:Development of the intestinal subtype of gastric adenocarcinoma is marked by a progression of histopathologic lesions. Residents of the Andean regions of Colombia are at high risk for gastric cancer. A cohort of 976 Colombian subjects was followed over 16 years examining effects of Helicobacter pylori eradication and treatment with antioxidants on progression of lesions. We performed methylation analysis of DNA from baseline antral biopsies from 104 subjects for whom follow-up data were available for at least 12 years. Methylation was quantitated for AMPH, CDKN2A, CDH1, EN1, EMX1, NKX6-1, PCDH10, RPRM, RSPO2, SORCS3, ZIC1, and ZNF610 genes, using Pyrosequencing. Levels of DNA methylation were associated with baseline diagnosis for AMPH, EMX1, RPRM, RSPO2, SORCS3, and ZNF610. After adjusting for baseline diagnosis and H. pylori infection, methylation levels of AMPH, PCDH10, RSPO2, and ZNF610 had progression coefficients that increased and P values that decreased over 6, 12, and 16 years. Methylation for SORCS3 was associated with progression at all 3 time points but without the continual strengthening of the effect. Scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes were unrelated to progression. Methylation levels of AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 predict progression of gastric lesions independent of the effect of duration of H. pylori infection, baseline diagnosis, gender of the patient, or scores for mononuclear leukocytes, polymorphonuclear leukocytes, or intraepithelial lymphocytes. DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress.
ISSN:1055-9965
1538-7755
DOI:10.1158/1055-9965.EPI-15-0388