Abstract |
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.
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Authors | Hiro Takahashi, Nahoko Kaniwa, Yoshiro Saito, Kimie Sai, Tetsuya Hamaguchi, Kuniaki Shirao, Yasuhiro Shimada, Yasuhiro Matsumura, Atsushi Ohtsu, Takayuki Yoshino, Anna Takahashi, Yoko Odaka, Misuzu Okuyama, Jun-ichi Sawada, Hiromi Sakamoto, Teruhiko Yoshida |
Journal | Journal of bioscience and bioengineering
(J Biosci Bioeng)
Vol. 116
Issue 6
Pg. 768-73
(Dec 2013)
ISSN: 1347-4421 [Electronic] Japan |
PMID | 23816762
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Antimetabolites, Antineoplastic
- ErbB Receptors
- Fluorouracil
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Topics |
- Algorithms
- Antimetabolites, Antineoplastic
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Colonic Neoplasms
(drug therapy, genetics)
- Computational Biology
- ErbB Receptors
(genetics)
- Female
- Fluorouracil
(pharmacology)
- Genome-Wide Association Study
- Genomics
- Humans
- Male
- Pharmacogenetics
- Polymorphism, Single Nucleotide
- Regression Analysis
- Stomach Neoplasms
(drug therapy, genetics)
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