DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study.
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) 1.02-3.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR = 2.0; 95% CI 1.09-3.65) and K751Q alleles (OR = 1.82; 95% CI 1.01-3.30) and XRCC1 R399Q (OR = 1.69; 95% CI 1.02-2.79) allele were associated with an increased risk for SCAG.


CONCLUSIONS
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.
Capellá
Gabriel
G
Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. capella@iconcologia.net
Pera
Guillem
G
Sala
Núria
N
Agudo
Antonio
A
Rico
Francisco
F
Del Giudicce
Giuseppe
G
Plebani
Mario
M
Palli
Domenico
D
Boeing
Heiner
H
Bueno-de-Mesquita
H Bas
HB
Carneiro
Fátima
F
Berrino
Franco
F
Vineis
Paolo
P
Tumino
Rosario
R
Panico
Salvatore
S
Berglund
Göran
G
Simán
Henrik
H
Nyrén
Olof
O
Hallmans
Goran
G
Martinez
Carmen
C
Dorronsoro
Miren
M
Barricarte
Aurelio
A
Navarro
Carmen
C
Quirós
José R
JR
Allen
Naomi
N
Key
Tim
T
Bingham
Sheila
S
Caldas
Carlos
C
Linseisen
Jakob
J
Nagel
Gabriele
G
Overvad
Kim
K
Tjonneland
Anne
A
Boshuizen
Hendriek C
HC
Peeters
Petra H M
PH
Numans
Mattijs E
ME
Clavel-Chapelon
Françoise
F
Trichopoulou
Antonia
A
Lund
Eiliv
E
Jenab
Mazda
M
Kaaks
Rudolf
R
Riboli
Elio
E
González
Carlos A
CA
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002299:Cardia / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D004260:DNA Repair / Q000235:genetics*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005757:Gastritis, Atrophic / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020116:Pepsinogen A / Q000097:blood; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D000907:Antibodies, Bacterial; D015415:Biomarkers; D020116:Pepsinogen A; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human