DNA Methylation Predicts Progression of Human Gastric Lesions.
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.


CONCLUSIONS
DNA methylation levels in AMPH, PCDH10, RSPO2, SORCS3, and ZNF610 may contribute to identification of persons with gastric lesions likely to progress.
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. barbara.schneider@vanderbilt.edu.
Barbara G
BG
Schneider
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Robertino
R
Mera
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
M Blanca
MB
Piazuelo
Fundación Valle del Lili, Cali, Colombia.
Juan C
JC
Bravo
Department of Pediatrics, Louisiana State University Health Sciences Center and Stanley Scott Cancer Center, New Orleans, Louisiana.
Jovanny
J
Zabaleta
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Alberto G
AG
Delgado
Department of Pathology, School of Medicine, Universidad del Valle, Cali, Colombia.
Luis E
LE
Bravo
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Veterans Affairs Tennessee Valley Healthcare System and Office of Medical Research, Department of Veterans Affairs, Nashville, Tennessee.
Keith T
KT
Wilson
Veterans Affairs Tennessee Valley Healthcare System and Office of Medical Research, Department of Veterans Affairs, Nashville, Tennessee. Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Wael
W
El-Rifai
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Richard M
RM
Peek
Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Pelayo
P
Correa
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D004311:Double-Blind Method; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005544:Forecasting; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control
D000900:Anti-Bacterial Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm