Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis.

Osamu Toyoshima,Yasuyuki Seto,Michiaki Kubo,Hiroharu Yamashita,Shuntaro Yoshida,Keitaro Matsuo,Chizu Tanikawa,Kazuhiko Koike,Koichi Matsuda,Ryuta Yamamoto,Kosuke Sakitani,Hidenobu Watanabe,Hidemi Ito

doi:10.18632/oncotarget.23278

Abstract

SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10–5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer. We also assessed the association of rs2294008 with PSCA mRNA expression in the gastric mucosa at various disease stages and found that rs2294008 was associated with PSCA expression (P = 1.3 × 10–12). H. pylori infection (P = 5.1 × 10–8) and eradication therapy (P < 1 × 10–11) resulted in the reduced and increased PSCA expression, respectively, indicating negative regulation of PSCA expression by H. pylori infection. PSCA expression was decreased in severe gastritis compared with mild gastritis only among T allele carriers. Our findings revealed the regulation of PSCA expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection.

Highlights

Helicobacter pylori colonizes the human gastric mucosa and has currently infected more than half of the entire human population [1]
Our findings revealed the regulation of Prostate Stem Cell Antigen (PSCA) expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection
The C allele of rs2294008 increases duodenal ulcer risk and the T allele increases gastric cancer and chronic atrophic gastritis risk [12], while rs2294008 was not associated with H. pylori susceptibility [13], suggesting the important role of this variation in clinical outcomes after H. pylori infection. rs2294008 was associated with PSCA mRNA expression in normal gastric tissues and gastric cancer

Summary

Introduction

Helicobacter pylori colonizes the human gastric mucosa and has currently infected more than half of the entire human population [1]. Previous genome-wide association studies have revealed the association of SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) with two H. pylori related diseases, gastric cancer and duodenal ulcer [10, 11]. The C allele of rs2294008 increases duodenal ulcer risk and the T allele increases gastric cancer and chronic atrophic gastritis risk [12], while rs2294008 was not associated with H. pylori susceptibility [13], suggesting the important role of this variation in clinical outcomes after H. pylori infection. Rs2294008 was associated with PSCA mRNA expression in normal gastric tissues and gastric cancer. We investigated rs2294008 and PSCA expression using germline DNA and gastric mucosal tissues at different disease stages and revealed novel roles of host genetic factor and bacterial infection in the disease pathogenesis

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