title: Genetic variation in PSCA and risk of gastric advanced preneoplastic lesions and cancer in relation to Helicobacter pylori infection.
abstract: SNPs in the Prostate Stem Cell Antigen (PSCA) gene have been found associated with gastric cancer (GC) risk in a genome-wide association study. This association has been replicated in several populations. In this study we assessed the impact of PSCA genotype on the risk of advanced gastric precancerous lesions and GC. We used baseline gastric histopathology data and DNA from frozen gastric biopsies of 2045 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela, and 180 cases of GC from the same area. We analyzed 3 SNPs in the PSCA gene (rs2294008, rs9297976 and rs12155758) which were previously found to be associated with GC risk in Europeans. The T allele of rs2294008 was found to be associated with a higher prevalence of atrophic gastritis (OR = 1.44; 95% CI 1.03-2.01 for the dominant model) and intestinal metaplasia (OR = 1.50; 95% CI 1.13-1.98 for the dominant model). We also confirmed the association with higher risk of gastric cancer (OR = 2.34; 95% CI 1.36-4.01 for the allele carriers). SNP rs12155758 was not associated with risk of gastric preneoplastic lesions, but we confirmed its association with higher GC risk (OR 1.95; 95% CI 1.29-2.97 for dominant model). We tested the relevance of the presence of the Helicobacter pylori cagA gene, which is known to increase the risk of more severe gastric lesions, but we did not find any clearcut interaction with PSCA SNPs in defining risk of gastric precancerous lesions or cancer.
authors.affiliation: German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kato
authors.forename: Martyn
authors.initials: M
authors.lastname: Plummer
authors.forename: Nubia
authors.initials: N
authors.lastname: Muñoz
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000150:complications / Q000235:genetics*; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D000951:Antigens, Neoplasm; D001426:Bacterial Proteins; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; C080866:cagA protein, Helicobacter pylori
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