Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 24, Issue 10, Pages 1607-1613Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-15-0388
Keywords
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Funding
- National Center for Research Resources [UL1 RR024975-01]
- National Center for Advancing Translational Sciences [2 UL2 TR000445-06]
- Department of Veterans Affairs [I01 BX001453]
- [P01 CA28842]
- [R01 CA77955]
- [R01 CA177372]
- [P01 CA116087]
- [P30 DK058404]
- [R01 DK053620]
- [R01 CA190612]
- [R01 DK58587]
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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. (C) 2015 AACR.
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