title: Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: results from the EPIC-EURGAST study.
abstract: A genome-wide study performed in a Japanese population identified a strong association between SNP rs2294008 (Met1Thr) in the Prostate Stem Cell Antigen gene (PSCA) and diffuse-type gastric cancer (GC). This association was validated in different Asian populations, and, very recently, a study has been published in Caucasians. In this study, we analyzed the association between PSCA variation and GC risk in Caucasians from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Six tagSNPs covering the PSCA gene region were genotyped in 411 incident gastric adenocarcinoma cases and 1530 matched controls from a nested case-control study in the EPIC cohort. Associations were analyzed by unconditional logistic regression, adjusting for age, sex and country. The T allele of rs2294008 in PSCA was found to be a highly significant risk factor for GC (per allele OR = 1.42, 95% CI: 1.23-1.66, p-value = 6.5 × 10(-6) ), particularly of the noncardia-type (per allele OR = 1.47, 95% CI: 1.19-1.81, p-value = 3 × 10(-4) ). At contrast with previous studies, no significant differences were observed between the diffuse (per allele OR = 1.54, 95% CI: 1.20-1.96, p-value = 5 × 10(-4) ) and the intestinal (per allele OR = 1.52, 95% CI: 1.20-1.93, p-value = 5 × 10(-4) ) GC histological subtypes. Although rs12155758 and rs9297976 were also found associated with GC, this association appeared to be due to linkage disequilibrium with rs2294008. Haplotype analysis did not provide additional information. These results confirm the association between variation in the promoter region of PSCA and GC risk in Caucasians and also indicate that the rs2294008 variant is a similar risk factor for both the diffuse and intestinal-types of GC.
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain. nsala@iconcologia.net
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.forename: Xavier
authors.initials: X
authors.lastname: Muñoz
authors.forename: Noemie
authors.initials: N
authors.lastname: Travier
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Karina
authors.initials: K
authors.lastname: Meidtner
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulos
authors.forename: Konstantine
authors.initials: K
authors.lastname: Tsiotas
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Zylis
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Mattjis E
authors.initials: ME
authors.lastname: Numans
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: J Ramon
authors.initials: JR
authors.lastname: Quirós
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Camen
authors.initials: C
authors.lastname: Navarro
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Roger
authors.initials: R
authors.lastname: Stenling
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
mesh_terms: D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D016481:Helicobacter Infections / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012737:Sex Factors; D012907:Smoking; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human