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.
Highlights
The Prostate Stem Cell Antigen (PSCA) gene is located on chromosome 8q24.2 and encodes a 123 amino acid cell surface protein with 30% homology to stem cell antigen type 2 (SCA-2), an immature lymphocyte cell surface marker [1]
Three previous genome-wide association study (GWAS) found a significant association of the T allele of rs2294008, a functional SNP in the PSCA gene, with the risk of gastric and bladder cancers [2,26,27] and the C allele for duodenal ulcer [28]
Several case-control studies confirmed the association of this SNP with gastric cancer (GC) in Asian and Caucasian populations
Summary
The Prostate Stem Cell Antigen (PSCA) gene is located on chromosome 8q24.2 and encodes a 123 amino acid cell surface protein with 30% homology to stem cell antigen type 2 (SCA-2), an immature lymphocyte cell surface marker [1]. PSCA is known to be expressed mainly in differentiating cells rather than stem cells [2,3]. PSCA is expressed in the epithelium of several organs, such as prostate, bladder, gallbladder and stomach. Its expression is specific to some populations of cells in the epithelia of these organs: in the gastric epithelium, the main expression site is the isthmus and neck regions, which contain differentiating cells. In particular the expression of PSCA is downregulated in the gastric tissue with intestinal metaplasia [2]
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