Identification of a candidate single-nucleotide polymorphism related to chemotherapeutic response through a combination of knowledge-based algorithm and hypothesis-free genomic data(BIOINFORMATICS)

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概要

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• Inter-individual variations in drug responses among patients are known to cause serious problems in medicine. Genome-wide association study (GWAS) is powerful for examining single-nucleotide polymorphisms (SNPs) and their relationships with drug response variations. However, no significant SNP has been identified using GWAS due to multiple testing problems. Therefore, we propose a combination method consisting of knowledge-based algorithm, two stages of screening, and permutation test for identifying SNPs in the present study. We applied this method to a genome-wide pharmacogenomics study for which 109,365 SNPs had been genotyped using Illumina Human-1 BeadChip for 119 gastric cancer patients treated with fluoropyrimidine. We identified rs2293347 in epidermal growth factor receptor (EGFR) is as a candidate SNP related to chemotherapeutic response. The p value for the rs2293347 was 2.19×10^<-5> for Fisher's exact test, and the p value was 0.00360 for the permutation test (multiple testing problems are corrected). Additionally, rs2293347 was clearly superior to clinical parameters and showed a sensitivity value of 55.0% and specificity value of 94.4% in the evaluation by using multiple regression models. Recent studies have shown that combination chemotherapy of fluoropyrimidine and EGFR-targeting agents is effective for gastric cancer patients highly expressing EGFR. These results suggest that rs2293347 is a potential predictive factor for selecting chemotherapies, such as fluoropyrimidine alone or combination chemotherapies.

著者

• Sai Kimie

  Division Of Biosignaling National Institute Of Health Sciences

• Kaniwa Nahoko

  Division Of Drugs National Institute Of Hygienic Sciences

• Saito Yoshiro

  Division Of Biochemistry And Immunochemistry National Institute Of Health Science

• Sawada Jun-ichi

  Division Of Biochemistry And Immunochemistry Natinal Institute Of Health Sciences

• Takahashi Hiro

  Department Of Biotechnology School Of Engineering Nagoya University

• Takahashi Hiro

  Department Of Biological Chemistry College Of Bioscience And Biotechnology Chubu University

• Yoshida Teruhiko

  Division Of Gastrointestinal Oncology/digestive Endoscopy National Cancer Center Hospital East

• TAKAHASHI Hiro

  Graduate School of Bioscience and Biotechnology, Chubu University

• Ohtsu Atsushi

  Department Of Gastroenterology And Gastrointestinal Oncology National Cancer Center Hospital East

• Yoshino Takayuki

  Department Of Gastroenterology And Gastrointestinal Oncology National Cancer Center Hospital East

• MATSUMURA Yasuhiro

  Division of Adult Health Science The National Institute of Health and Nutrition, Tokyo

• Shimada Yasuhiro

  Gastrointestinal Medical Oncology Division, National Cancer Center Hospital

• Matsumura Yasuhiro

  Division of Developental Therapeutics, Research Center for Innovative Oncology, National Cancer Center Hospital East

• 高橋 広夫

  千葉大院・園芸

• Shirao Kuniaki

  Gastrointestinal Medical Oncology Division, National Cancer Center Hospital

• Saito Yoshiro

  Division of Medical Safety Science, National Institute of Health Sciences

• Hamaguchi Tetsuya

  Gastrointestinal Medical Oncology Division, National Cancer Center Hospital

• Takahashi Anna

  Plant Biology Research Center, Chubu University

• Odaka Yoko

  Division of Genetics, National Cancer Center Research Institute

• Okuyama Misuzu

  Division of Genetics, National Cancer Center Research Institute

• Sakamoto Hiromi

  Division of Genetics, National Cancer Center Research Institute

• Kaniwa Nahoko

  Division of Medical Safety Science, National Institute of Health Sciences

• Ohtsu Atsushi

  Department of Gastrointestinal Oncology, National Cancer Center Hospital East

• Yoshino Takayuki

  Department of Gastrointestinal Oncology, National Cancer Center Hospital East

• Sai Kimie

  Division of Medical Safety Science, National Institute of Health Sciences

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