DNA Methylation Predicts Progression of Human Gastric Lesions.

Schneider BG, Mera R, Piazuelo MB, Bravo JC, Zabaleta J, Delgado AG, Bravo LE, Wilson KT, El-Rifai W, Peek RM, Correa P
Cancer Epidemiol Biomarkers Prev. 2015 24 (10): 1607-13

PMID: 26269563 · PMCID: PMC4592454 · DOI:10.1158/1055-9965.EPI-15-0388

BACKGROUND - 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.

METHODS - 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.

RESULTS - 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.

CONCLUSIONS - 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.

IMPACT - DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress.

©2015 American Association for Cancer Research.

MeSH Terms (21)

Adenocarcinoma Adult Anti-Bacterial Agents Biomarkers, Tumor Chemoprevention Disease Progression DNA, Neoplasm DNA Methylation Double-Blind Method Endoscopy, Gastrointestinal Female Forecasting Gastric Mucosa Helicobacter Infections Helicobacter pylori Humans Male Middle Aged Polymerase Chain Reaction Precancerous Conditions Stomach Neoplasms

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