Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

被引：56

作者：

Balassiano, Karen ^{[1
]}

Lima, Sheila ^{[1
]}

Jenab, Mazda ^{[1
]}

Overvad, Kim ^{[2
]}

Tjonneland, Anne ^{[3
]}

Boutron-Ruault, Marie Christine ^{[4
,5
]}

Clavel-Chapelon, Francoise ^{[4
,5
]}

Canzian, Federico ^{[6
]}

Kaaks, Rudolf ^{[6
]}

Boeing, Heiner ^{[7
]}

Meidtner, Karina ^{[7
]}

Trichopoulou, Antonia ^{[8
,9
]}

Laglou, Pagona ^{[8
,9
]}

Vineis, Paolo ^{[10
]}

Panico, Salvatore ^{[11
]}

Palli, Domenico

Grioni, Sara ^{[12
]}

Tumino, Rosario ^{[13
,14
]}

Lund, Eiliv ^{[15
]}

Bueno-de-Mesquita, H. Bas ^{[16
,17
]}

Numans, Mattjis E. ^{[18
]}

Peeters, Petra H. M. ^{[18
]}

Ramon Quiros, J. ^{[19
]}

Sanchez, Maria-Jose ^{[20
]}

Navarro, Carmen ^{[21
]}

Ardanaz, Eva ^{[22
]}

Dorronsoro, Miren

Hallmans, Goran ^{[23
]}

Stenling, Roger ^{[24
]}

Ehrnstrom, Roy ^{[25
]}

Regner, Sara ^{[25
]}

Allen, Naomi E. ^{[26
]}

Travis, Ruth C. ^{[26
]}

Khaw, Kay-Tee ^{[31
]}

Offerhaus, G. Johan A. ^{[27
]}

Sala, Nuria ^{[28
]}

Riboli, Elio ^{[29
]}

Hainaut, Pierre ^{[1
]}

Scoazec, Jean-Yves ^{[30
]}

Sylla, Bakary S. ^{[1
]}

Gonzalez, Carlos A.

Herceg, Zdenko ^{[1
]}

机构：

[1] Int Agcy Res Canc, Epigenet Grp, F-69008 Lyon, France

[2] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, Aarhus, Denmark

[3] Danish Canc Soc, Inst Canc Epidemiol Diet Canc & Hlth, Copenhagen, Denmark

[4] Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth, Villejuif, France

[5] Paris S Univ, Villejuif, France

[6] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany

[7] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany

[8] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, Athens, Greece

[9] Hellen Hlth Fdn, Athens, Greece

[10] Univ Turin, Turin, Italy

[11] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[12] Fdn IRCCS Ist Nazl Tumori, Dept Nutr Epidemiol Unit, Milan, Italy

[13] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy

[14] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy

[15] Univ Tromso, Dept Community Med, N-9001 Tromso, Norway

[16] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands

[17] UMCU, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[18] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[19] Publ Hlth & Hlth Planning Directorate, Asturias, Spain

[20] Andalusian Sch Publ Hlth, Granada, Spain

[21] Murcia Hlth Council, Dept Epidemiol, Murcia, Spain

[22] Navarre Publ Hlth Inst, Pamplona, Spain

[23] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden

[24] Umea Univ, Dept Med Biosci, Umea, Sweden

[25] Lund Univ, Dept Surg, Skane Univ Hosp Malmo, Malmo, Sweden

[26] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England

[27] Univ Med Ctr, Dept Pathol, NL-3508 GA Utrecht, Netherlands

[28] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain

[29] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England

[30] Hop Edouard Herriot, Lyon, France

[31] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

来源：

CANCER LETTERS | 2011年 / 311卷 / 01期

基金：

美国国家卫生研究院;

关键词：

DNA methylation; Gastric cancer; Biomarkers; Prospective study; GLYCINE N-METHYLTRANSFERASE; CPG ISLAND HYPERMETHYLATION; HELICOBACTER-PYLORI; LUNG-CANCER; SUSCEPTIBILITY LOCUS; DIETARY FACTORS; RISK-FACTORS; ADENOCARCINOMA; TRACT; POLYMORPHISMS;

D O I：

10.1016/j.canlet.2011.06.038

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：85 / 95

页数：11

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