Περίληψη:
Helicobacter pylori is a recognized causal factor of noncardia gastric
cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are
recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates
the transcription of pro-inflammatory cytokines to elicit an immune
response. Single nucleotide polymorphisms (SNPs) in these genes have
been associated with GC in different populations. We genotyped 30 SNPs
of these genes, in 365 gastric adenocarcinomas and 1,284 matched
controls from the European Prospective Investigation into Cancer cohort.
The association with GC and its histological and anatomical subtypes was
analyzed by logistic regression and corrected for multiple comparisons.
Using a log-additive model, we found a significant association between
SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the
multiple comparisons tests only the NOD2 region remained significant
(p=0.009). Analysis according to anatomical subtypes revealed NOD2 and
NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with
cardia GC, while analysis according to histological subtypes showed that
CD14 was associated with intestinal but not diffuse GC. The multiple
comparisons tests confirmed the association of NOD2 with noncardia GC
(p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in
agreement with single SNP results for NOD2 and CD14 genes. From these
results, we conclude that genetic variation in NOD2 associates with
noncardia GC while variation in CD14 is associated with cardia GC.
What’s new? Variations in immune genes appear to play an important role
in determining susceptibility to gastric cancer linked to Helicobacter
pylori colonization of gastric mucosa. However, little is known about
the influence of variation on anatomical localization and histological
subtype of this malignancy. The results of this study first confirm that
NOD2 and CD14, which encode proteins that recognize H. pylori
lipopolysaccharide and peptidoglycan, are significantly associated with
gastric cancer risk and second indicate that NOD2 associates with
noncardia and CD14 with cardia gastric cancer. The differential effects
of variation on the anatomical localization of disease warrant further
investigation.
Συγγραφείς:
Companioni, Osmel
Bonet, Catalina
Munoz, Xavier
Weiderpass,
Elisabete
Panico, Salvatore
Tumino, Rosario
Palli, Domenico
and Agnoli, Claudia
Vineis, Paolo
Boutron-Ruault,
Marie-Christine
Racine, Antoine
Clavel-Chapelon, Francoise and
Travis, Ruth C.
Khaw, Kay-Tee
Riboli, Elio
Murphy, Neil and
Vergnaud, Anne-Claire
Trichopoulou, Antonia
Benetou, Vassiliki
and Trichopoulos, Dimitrios
Lund, Eiliv
Johansen, Dorthe and
Lindkvist, Bjoern
Johansson, Mattias
Sund, Malin
Ardanaz,
Eva
Sanchez-Cantalejo, Emilio
Huerta, Jose M.
Dorronsoro,
Miren
Ramon Quiros, Jose
Tjonneland, Anne
Mortensen, Lotte
Maxild
Overvad, Kim
Chang-Claude, Jenny
Rizzato, Cosmeri and
Boeing, Heiner
De Mesquita, H. Bas Bueno
Siersema, Peter and
Peeters, Petra H. M.
Numans, Mattijs E.
Carneiro, Fatima and
Licaj, Idlir
Freisling, Heinz
Sala, Nuria
Gonzalez, Carlos
A.
