Abstract 3746: Prostate stem cell antigen is associated with gastric cancer in Caucasians: Results from the EPIC-EURGAST study

Background. 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 has been validated in different Asian populations but no study has yet been conducted in Caucasians. Objective. To analyze the association between PSCA variants and gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods. As part of a wider study in which we used the Illumina GoldenGate technology to genotype 1287 SNPs in 249 candidate genomic regions, we genotyped six tagSNPs covering the PSCA gene region in 411 incident gastric adenocarcinoma cases and 1530 matched controls from a nested case-control study in the European EPIC cohort. Among GC cases, 28% were in the cardia or in the gastroesophageal junction, 48% were noncardia and 24% were unspecified. Regarding the histological type, 36% were intestinal, 35% were diffuse and 29% were unspecified. After quality control analysis and data filtering, association was analyzed by unconditional logistic regression, adjusting for age, sex and country. Results. The T allele of rs2294008 in PSCA (frequency of 0.44 in controls and 0.53 in cases) was found to be a significant risk factor for GC (per allele OR=1.42, 95%CI:1.23-1.6; uncorrected p-value=6.5×10-6; Bonferroni adjusted p-value=0.0126). The A allele of rs12155758 also appeared to increase GC risk, while the C allele of rs9297976, in LD with rs2294008, was inversely associated with GC. These 3 SNPs jointly cover 92% of the common variation (MAF≥0.05) within 10 kb around PSCA in Caucasians. Haplotype analysis did not provide additional information. No statistically significant differences were observed in the effect of rs2294008 between diffuse (OR=1.54, 95%CI:1.20-1.96; p-value=0.0005) and intestinal-types (OR=1.52, 95%CI:1.20-1.93; p-value=0.0005), or between cardia (OR=1.19, 95%CI:0.91-1.56; p-value=0.20) and noncardia (OR=1.47, 95%CI:1.19-1.81; p-value=0.0003) sub-sites, although the associations were stronger in noncardia GC. Conclusions. Variation in the promoter region of PSCA, specifically the functional rs2294008 variant, is associated with GC risk in Caucasians. Supported by “LaCaixa” (BM06-130-0); Spanish Ministry of Health (PI070130 and PI081420); European Commission FP5 (ref.QLG1-CT-2001-01049). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3746. doi:10.1158/1538-7445.AM2011-3746