GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy
| Autor: | Yasumasa Niwa, Mariko Naito, Takahisa Kawaguchi, Hidemi Ito, Michael C. Wu, Yoshiyuki Watanabe, Masahiro Tajika, Yukihide Momozawa, Keitaro Matsuo, Michiaki Kubo, Takeshi Nishiyama, Fumihiko Matsuda, Teruhide Koyama, Daisuke Matsui, Isao Oze, Sadao Suzuki, Hiroko Nakagawa-Senda, Masahiro Nakatochi, Ryosuke Fujii, Asahi Hishida, Kenji Wakai, Tomotaka Ugai |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Atrophic gastritis Stomach Diseases Single-nucleotide polymorphism Genome-wide association study Locus (genetics) Biology GPI-Linked Proteins Polymorphism Single Nucleotide Helicobacter Infections Cohort Studies 03 medical and health sciences 0302 clinical medicine Japan Antigens Neoplasm Risk Factors Internal medicine medicine Humans SNP Genetic Predisposition to Disease Aged Genetic association Helicobacter pylori Incidence General Medicine Middle Aged Prognosis medicine.disease biology.organism_classification Neoplasm Proteins Prostate Stem Cell Antigen 030104 developmental biology Genetic Loci Female 030211 gastroenterology & hepatology Atrophy Follow-Up Studies Genome-Wide Association Study |
| Zdroj: | Carcinogenesis. 40:661-668 |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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