title: NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to gastric cancer in an Italian population.
abstract: 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.
authors.affiliation: Clinical Pathology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Angeletti
authors.forename: Sara
authors.initials: S
authors.lastname: Galluzzo
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruzzo
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferraro
authors.forename: Chiara
authors.initials: C
authors.lastname: Spoto
authors.forename: Giulia
authors.initials: G
authors.lastname: Lorino
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Graziano
authors.forename: Alice
authors.initials: A
authors.lastname: Calvieri
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Francesco
authors.initials: F
authors.lastname: Pantano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Giordano
authors.initials: G
authors.lastname: Dicuonzo
mesh_terms: 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
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein