Prostate stem-cell antigen gene is associated with diffuse and intestinal gastric cancer in Caucasians: Results from the EPIC-EURGAST study

Núria Sala, Xavier Muñoz, Noemie Travier, Antonio Agudo, Eric J. Duell, Víctor Moreno, Kim Overvad, Anne Tjonneland, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Federico Canzian, Rudolf Kaaks, Heiner Boeing, Karina Meidtner, Antonia Trichopoulos, Konstantine Tsiotas, Dimosthenis Zylis, Paolo Vineis, Salvatore Panico, Domenico PalliVittorio Krogh, Rosario Tumino, Eiliv Lund, H. Bas Bueno-De-Mesquita, Mattjis E. Numans, Petra H M Peeters, J. Ramon Quirós, María José Sánchez, Camen Navarro, Eva Ardanaz, Miren Dorronsoro, Göran Hallmans, Roger Stenling, Jonas Manjer, Naomi E. Allen, Ruth C. Travis, Kay Tee Khaw, Mazda Jenab, G. Johan A Offerhaus, Elio Riboli, Carlos A. González

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2417-2427
Number of pages11
JournalInternational Journal of Cancer
Volume130
Issue number10
DOIs
StatePublished - May 15 2012
Externally publishedYes

Keywords

  • Caucasians
  • gastric adenocarcinoma
  • genetic susceptibility
  • PSCA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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