DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study

被引：63

作者：

Capella, Gabriel ^{[1
]}

Pera, Guillem ^{[2
]}

Sala, Nuria ^{[1
,3
]}

Agudo, Antonio ^{[2
]}

Rico, Francisco ^{[1
,3
]}

Del Giudicce, Giuseppe ^{[4
]}

Plebani, Mario ^{[5
]}

Palli, Domenico ^{[6
]}

Boeing, Heiner ^{[7
]}

Bueno-de-Mesquita, H. Bas ^{[8
]}

Carneiro, Fatima ^{[9
,10
]}

Berrino, Franco ^{[11
]}

Vineis, Paolo ^{[12
]}

Tumino, Rosario ^{[13
]}

Panico, Salvatore ^{[14
]}

Berglund, Goran ^{[15
]}

Siman, Henrik ^{[15
]}

Nyren, Olof ^{[16
]}

Hallmans, Goran ^{[17
]}

Martinez, Carmen ^{[18
]}

Dorronsoro, Miren ^{[19
]}

Barricarte, Aurelio ^{[20
]}

Navarro, Carmen ^{[21
]}

Quiros, Jose R. ^{[22
]}

Allen, Naomi ^{[23
]}

Key, Tim ^{[23
]}

Bingham, Sheila

Caldas, Carlos ^{[24
]}

Linseisen, Jakob ^{[25
,26
]}

Nagel, Gabriele ^{[25
,26
]}

Overvad, Kim ^{[27
]}

Tjonneland, Anne ^{[28
]}

Boshuizen, Hendriek C. ^{[8
]}

Peeters, Petra H. M. ^{[29
]}

Numans, Mattijs E. ^{[29
]}

Clavel-Chapelon, Francoise ^{[30
]}

Trichopoulou, Antonia ^{[31
]}

Lund, Eiliv ^{[32
]}

Jenab, Mazda ^{[33
]}

Kaaks, Rudolf ^{[33
]}

Riboli, Elio ^{[33
,34
]}

Gonzalez, Carlos A. ^{[2
]}

机构：

[1] Catalan Inst Oncol, Translat Res Lab, IDIBELL, Barcelona, Spain

[2] Catalan Inst Oncol, Dept Epidemiol, IDIBELL, Barcelona, Spain

[3] Inst Recerca Oncol, IDIBELL, Ctr Mol & Med Genet, Barcelona, Spain

[4] CHIRON Vaccines, IRIS Res Ctr, Siena, Italy

[5] Azienda Osped Padova, Serv Med Lab, Padua, Italy

[6] CSPO Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, Florence, Italy

[7] German Inst Human Nutr, Potsdam, Germany

[8] Natl Inst Publ Hlth & Environm, Ctr Informat Technol & Methodol, NL-3720 BA Bilthoven, Netherlands

[9] Univ Porto, IPATIMUP, Inst Pathol & Mol Immunol, P-4100 Oporto, Portugal

[10] Med Fac HS Joao, Oporto, Portugal

[11] Ist Tuimori, Epidemiol Unit, Milan, Italy

[12] Univ Turin, I-10124 Turin, Italy

[13] Azienda Osped Civile MP, Canc Registry, Arezzo, Ragusa, Italy

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

[15] Lund Univ, Malmo Diet & Canc Study, Malmo, Sweden

[16] Umea Univ, Dept Med Biosci, S-90187 Umea, Sweden

[17] Umea Univ, Dept Nutr Res, S-90187 Umea, Sweden

[18] Andalusian Sch Publ Hlth, Granada, Spain

[19] Dept Publ Hlth Guipuzkoa, San Sebastian, Spain

[20] Publ Hlth Inst Navarra, Pamplona, Spain

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

[22] Publ Hlth Directorate Hlth & Social Serv Asturias, Oviedo, Spain

[23] Univ Oxford, Epidemiol Unit, Canc Res UK, Oxford, England

[24] Univ Cambridge, Canc Genom Program, Dept Oncol, Hutchison MRC Res Ctr, Cambridge, England

[25] German Canc Res Ctr, Unit Human Nutr & Canc Prevent, D-6900 Heidelberg, Germany

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

[27] Univ Aarhus, Inst Epidemiol & Social Med, Aarhus, Denmark

[28] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark

[29] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[30] Inst Gustave Roussy, INSERM, U 521, F-94805 Villejuif, France

[31] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece

[32] Univ Tromso, Inst Community Med, Tromso, Norway

[33] Int Agcy Res Canc, Unit Nutr & Canc, F-69372 Lyon, France

[34] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England

来源：

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | 2008年 / 37卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1093/ije/dyn145

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Background The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG). Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls. Controls with SCAG (n 91), as defined by low pepsinogen A (PGA) levels, and controls with no SCAG (n 1061) were also compared. Twelve polymorphisms at DNA repair genes (MSH2, MLH1, XRCC1, OGG1 and ERCC2) and TP53 gene were analysed. Antibodies against Helicobacter pylori were measured. Results No association was observed for any of these polymorphisms with stomach cancer risk. However, ERCC2 K751Q polymorphism was associated with an increased risk for non-cardial neoplasm [odds ratio (OR) 1.78; 95 confidence interval (CI) 1.023.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR 2.0; 95 CI 1.093.65) and K751Q alleles (OR 1.82; 95 CI 1.013.30) and XRCC1 R399Q (OR 1.69; 95 CI 1.022.79) allele were associated with an increased risk for SCAG. Conclusion Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. A concordant result was observed for subjects with low PGA levels. XRCC1 allele was associated also with SCAG. This is the first prospective study suggesting that individual variation in DNA repair may be relevant for gastric carcinogenesis, a finding that will require further confirmation validation in larger independent studies.

引用

页码：1316 / 1325

页数：10

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