TY - JOUR
T1 - Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis
AU - Toyoshima, Osamu
AU - Tanikawa, Chizu
AU - Yamamoto, Ryuta
AU - Watanabe, Hidenobu
AU - Yamashita, Hiroharu
AU - Sakitani, Kosuke
AU - Yoshida, Shuntaro
AU - Kubo, Michiaki
AU - Matsuo, Keitaro
AU - Ito, Hidemi
AU - Koike, Kazuhiko
AU - Seto, Yasuyuki
AU - Matsuda, Koichi
N1 - Funding Information:
This work was supported by Ministry of Education, Culture, Sports, Science and Technology of Japan [25134707 and 16H01566 to Ko.M., 15K14377 to C.T.]. This study was also supported by funding from the Tailor-Made Medical Treatment with the BBJ Project from Japan Agency for Medical Research and Development, AMED (from April 2015), and the Ministry of Education, Culture, Sports, Science, and Technology of Japan (from April 2003 to March 2015).
PY - 2018
Y1 - 2018
N2 - 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. pyloriinfected 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.
AB - 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. pyloriinfected 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.
UR - http://www.scopus.com/inward/record.url?scp=85040183949&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040183949&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.23278
DO - 10.18632/oncotarget.23278
M3 - Article
AN - SCOPUS:85040183949
VL - 9
SP - 3936
EP - 3945
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 3
ER -