title: Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.
abstract: Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.
authors.affiliation: Instituto De Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.|CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.
authors.forename: María Asunción
authors.initials: MA
authors.lastname: García-González
authors.affiliation: CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.|Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad Del País Vasco (UPV/EHU), San Sebastián, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: Department of Gastroenterology, Hospital Universitario De Canarias, Instituto Universitario De Tecnologías Biomédicas (ITB), Centro De Investigación Biomédica De Canarias (CIBICAN), Tenerife, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Quintero
authors.affiliation: Department of Gastroenterology, Hospital San Jorge, Huesca, Spain.
authors.forename: Santos
authors.initials: S
authors.lastname: Santolaria
authors.affiliation: CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.|Department of Microbiology, Faculty of Medicine, Hospital Clínico Universitario, Zaragoza, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Benito
authors.affiliation: Instituto De Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.|CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.
authors.forename: Mark
authors.initials: M
authors.lastname: Strunk
authors.affiliation: CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.|Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Sopeña
authors.affiliation: Department of Gastroenterology, Hospital Obispo Polanco, Teruel, Spain.
authors.forename: Concha
authors.initials: C
authors.lastname: Thomson
authors.affiliation: Department of Gastroenterology, Hospital Del Sol, Marbella, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Pérez-Aisa
authors.affiliation: Department of Gastroenterology, Hospital Universitario De Canarias, Instituto Universitario De Tecnologías Biomédicas (ITB), Centro De Investigación Biomédica De Canarias (CIBICAN), Tenerife, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Nicolás-Pérez
authors.affiliation: Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad Del País Vasco (UPV/EHU), San Sebastián, Spain.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hijona
authors.affiliation: CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Carrera-Lasfuentes
authors.affiliation: Instituto De Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.|CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Piazuelo
authors.affiliation: CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Jiménez
authors.affiliation: Department of Gastroenterology, Complejo Hospitalario, León, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Espinel
authors.affiliation: Department of Gastroenterology, Hospital Parc Tauli, Sabadell, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Campo
authors.affiliation: Department of Gastroenterology, Hospital 12 De Octubre, Madrid, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Manzano
authors.affiliation: Department of Gastroenterology, Hospital Clínico Universitario, Salamanca, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Geijo
authors.affiliation: Department of Gastroenterology, Hospital Clinic I Provincial, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pellise
authors.affiliation: Department of Gastroenterology, Hospital De Cruces, Barakaldo, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zaballa
authors.affiliation: Department of Gastroenterology, Hospital Josep Trueta, Girona, Spain.
authors.forename: Ferrán
authors.initials: F
authors.lastname: González-Huix
authors.affiliation: Department of Gastroenterology, Mutua De Tarrasa, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Espinós
authors.affiliation: Department of Gastroenterology, Hospital De Mataró, Mataró, Spain.
authors.forename: Llúcia
authors.initials: L
authors.lastname: Titó
authors.affiliation: Department of Gastroenterology, Hospital Del Mar, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Barranco
authors.affiliation: Department of Oncology, Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pazo-Cid
authors.affiliation: Instituto De Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.|CIBER De Enfermedades Hepáticas Y Digestivas (CIBERehd), Zaragoza, Spain.|Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.|Department of Medicine, Universidad de Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics*; D016022:Case-Control Studies; D004381:Duodenal Ulcer / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012306:Risk; D012307:Risk Factors; D013030:Spain; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human
keywords: Helicobacter pylori; PSCA; duodenal ulcer; gastric cancer; polymorphism