TY - JOUR
T1 - GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy
AU - Hishida, Asahi
AU - Ugai, Tomotaka
AU - Fujii, Ryosuke
AU - Nakatochi, Masahiro
AU - Wu, Michael C.
AU - Ito, Hidemi
AU - Oze, Isao
AU - Tajika, Masahiro
AU - Niwa, Yasumasa
AU - Nishiyama, Takeshi
AU - Nakagawa-Senda, Hiroko
AU - Suzuki, Sadao
AU - Koyama, Teruhide
AU - Matsui, Daisuke
AU - Watanabe, Yoshiyuki
AU - Kawaguchi, Takahisa
AU - Matsuda, Fumihiko
AU - Momozawa, Yukihide
AU - Kubo, Michiaki
AU - Naito, Mariko
AU - Matsuo, Keitaro
AU - Wakai, Kenji
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved.
PY - 2019/7/4
Y1 - 2019/7/4
N2 - Although recent genome-wide association studies (GWASs) have identified genetic variants associated with Helicobacter pylori (HP)-induced gastric cancer, few studies have examined the genetic traits associated with the risk of HP-induced gastric precancerous conditions. This study aimed to elucidate genetic variants associated with these conditions using a genome-wide approach. Data from four sites of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were used in the discovery phase (Stage I); two datasets from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center 2 (HERPACC2) study were used in the replication phases (Stages II and III) and SKAT (SNP-set Kernel Association Test) and single variant-based GWASs were conducted for the risks of gastric atrophy (GA) and severe GA defined by serum pepsinogen (PG) levels, and PG1 and PG1/2 ratios. In the gene-based SKAT in Stage I, prostate stem cell antigen (PSCA) was significantly associated with the risks of GA and severe GA, and serum PG1/2 level by linear kernel [false discovery rate (FDR) = 0.011, 0.230 and 7.2 × 10-7, respectively]. The single variant-based GWAS revealed that nine PSCA single nucleotide polymorphisms (SNPs) fulfilled the genome-wide significance level (P < 5 × 10-8) for the risks of both GA and severe GA in the combined study, although most of these associations did not reach genome-wide significance in the discovery or validation cohort on their own. GWAS for serum PG1 levels and PG1/2 ratios revealed that the PSCA rs2920283 SNP had a striking P-value of 4.31 × 10-27 for PG1/2 ratios. The present GWAS revealed the genetic locus of PSCA as the most significant locus for the risk of HP-induced GA, which confirmed the recently reported association in Europeans.
AB - Although recent genome-wide association studies (GWASs) have identified genetic variants associated with Helicobacter pylori (HP)-induced gastric cancer, few studies have examined the genetic traits associated with the risk of HP-induced gastric precancerous conditions. This study aimed to elucidate genetic variants associated with these conditions using a genome-wide approach. Data from four sites of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were used in the discovery phase (Stage I); two datasets from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center 2 (HERPACC2) study were used in the replication phases (Stages II and III) and SKAT (SNP-set Kernel Association Test) and single variant-based GWASs were conducted for the risks of gastric atrophy (GA) and severe GA defined by serum pepsinogen (PG) levels, and PG1 and PG1/2 ratios. In the gene-based SKAT in Stage I, prostate stem cell antigen (PSCA) was significantly associated with the risks of GA and severe GA, and serum PG1/2 level by linear kernel [false discovery rate (FDR) = 0.011, 0.230 and 7.2 × 10-7, respectively]. The single variant-based GWAS revealed that nine PSCA single nucleotide polymorphisms (SNPs) fulfilled the genome-wide significance level (P < 5 × 10-8) for the risks of both GA and severe GA in the combined study, although most of these associations did not reach genome-wide significance in the discovery or validation cohort on their own. GWAS for serum PG1 levels and PG1/2 ratios revealed that the PSCA rs2920283 SNP had a striking P-value of 4.31 × 10-27 for PG1/2 ratios. The present GWAS revealed the genetic locus of PSCA as the most significant locus for the risk of HP-induced GA, which confirmed the recently reported association in Europeans.
UR - http://www.scopus.com/inward/record.url?scp=85068923314&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068923314&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgz016
DO - 10.1093/carcin/bgz016
M3 - Article
C2 - 30753327
AN - SCOPUS:85068923314
SN - 0143-3334
VL - 40
SP - 661
EP - 668
JO - Carcinogenesis
JF - Carcinogenesis
IS - 5
ER -