TY - JOUR
T1 - Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
AU - Balassiano, Karen
AU - Lima, Sheila
AU - Jenab, Mazda
AU - Overvad, Kim
AU - Tjonneland, Anne
AU - Boutron-Ruault, Marie Christine
AU - Clavel-Chapelon, Francoise
AU - Canzian, Federico
AU - Kaaks, Rudolf
AU - Boeing, Heiner
AU - Meidtner, Karina
AU - Trichopoulou, Antonia
AU - Laglou, Pagona
AU - Vineis, Paolo
AU - Panico, Salvatore
AU - Palli, Domenico
AU - Grioni, Sara
AU - Tumino, Rosario
AU - Lund, Eiliv
AU - Bueno-de-Mesquita, H. Bas
AU - Numans, Mattjis E.
AU - Peeters, Petra H. M.
AU - Ramon Quiros, J.
AU - Sanchez, Maria-Jose
AU - Navarro, Carmen
AU - Ardanaz, Eva
AU - Dorronsoro, Miren
AU - Hallmans, Goran
AU - Stenling, Roger
AU - Ehrnström, Roy
AU - Regnér, Sara
AU - Allen, Naomi E.
AU - Travis, Ruth C.
AU - Khaw, Kay-Tee
AU - Offerhaus, G. Johan A.
AU - Sala, Nuria
AU - Riboli, Elio
AU - Hainaut, Pierre
AU - Scoazec, Jean-Yves
AU - Sylla, Bakary S.
AU - Gonzalez, Carlos A.
AU - Herceg, Zdenko
N1 - The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Pathology (Malmö) (013031000)
PY - 2011
Y1 - 2011
N2 - Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological subtype and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
AB - Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological subtype and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
KW - DNA methylation
KW - Gastric cancer
KW - Biomarkers
KW - Prospective study
U2 - 10.1016/j.canlet.2011.06.038
DO - 10.1016/j.canlet.2011.06.038
M3 - Article
C2 - 21831520
SN - 1872-7980
VL - 311
SP - 85
EP - 95
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
