NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to gastric cancer in an Italian population.
In the present case-control study we investigated the potential role of CARD15 R702W, G908R, and 1007fs polymorphisms in Italian gastric cancer patients. The study population consisted of 170 gastric cancer patients and 156 controls. Unconditional regression (odds ratios and 95% confidence interval) was used to investigate the association of the studied polymorphisms with gastric cancer. Higher allele frequencies of R702W and 1007fs polymorphisms were observed in patients with gastric cancer compared with controls (8.53 vs 2.3 and 9.4 vs 0.7, respectively). CARD15 R702W and 1007fs polymorphisms were significantly correlated with gastric cancer incidence (p < 0.0001, p < 0.0001, respectively). No correlation was found upon analyzing the G908R single nucleotide polymorphism (SNP). Our study reports an increased susceptibility to gastric cancer in Italian populations when R702W and 1007fs polymorphisms in the coding region of CARD15 are present. The interaction between NOD-induced proinflammatory cytokines on gastric mucosa and environmental carcinogens could represent one of the mechanisms by which CARD15 polymorphisms increase the susceptibility to gastric cancer. Meta-analyses of these SNPs and further analyses of additional polymorphisms/haplotypes in NOD genes will help determine their role in carcinogenesis.
Angeletti
Silvia
S
Clinical Pathology, University Campus Bio-Medico, Rome, Italy.
Galluzzo
Sara
S
Santini
Daniele
D
Ruzzo
Annamaria
A
Vincenzi
Bruno
B
Ferraro
Elisabetta
E
Spoto
Chiara
C
Lorino
Giulia
G
Graziano
Nicoletta
N
Calvieri
Alice
A
Magnani
Mauro
M
Graziano
Francesco
F
Pantano
Francesco
F
Tonini
Giuseppe
G
Dicuonzo
Giordano
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007558:Italy; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein