Περίληψη:
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.
Συγγραφείς:
Capella, Gabriel
Pera, Guillem
Sala, Nuria
Agudo, Antonio
and Rico, Francisco
Del Giudicce, Giuseppe
Plebani, Mario and
Palli, Domenico
Boeing, Heiner
Bueno-de-Mesquita, H. Bas and
Carneiro, Fatima
Berrino, Franco
Vineis, Paolo
Tumino,
Rosario
Panico, Salvatore
Berglund, Goran
Siman, Henrik and
Nyren, Olof
Hallmans, Goran
Martinez, Carmen
Dorronsoro,
Miren
Barricarte, Aurelio
Navarro, Carmen
Quiros, Jose R.
and Allen, Naomi
Key, Tim
Bingham, Sheila
Caldas, Carlos and
Linseisen, Jakob
Nagel, Gabriele
Overvad, Kim
Tjonneland,
Anne
Boshuizen, Hendriek C.
Peeters, Petra H. M.
Numans,
Mattijs E.
Clavel-Chapelon, Francoise
Trichopoulou, Antonia and
Lund, Eiliv
Jenab, Mazda
Kaaks, Rudolf
Riboli, Elio and
Gonzalez, Carlos A.
