2017 Fiscal Year Final Research Report
Pharmacogenomic analysis of biomarker that predict adverse events associated with 5-fluorouracil
| Project/Area Number |
15K10128
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内藤 剛 東北大学, 医学系研究科, 准教授 (50291258)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | DPYD / MTHFR / OPRT / TYMS / 5-FU / splicing |
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| Outline of Final Research Achievements |
The aim of this study was to investigate the association between 5-fluorouracil (5-FU)-related adverse events (AEs) in Japanese patients with gastrointestinal cancer treated with 5-FU and the patient genotypes DPYD, MTHFR, OPRT, and TYMS. Methods: Sequence analyses of 33 gene polymorphisms in four genes were performed using genomic DNA extracted from peripheral blood mononuclear cells of 88 patients with gastric (n = 30) or colorectal (n = 58) cancer. The associations between the incidence of AEs and each genotype were statistically analyzed. Results: The patients carrying any one of three DPYD SNPs (c.496A>G, c.1905+1G>A, and c.2303C>A) showed statistically significant associations with the incidence of AEs, especially fatigue, and the MTHFR SNP c.1298A>C was significantly associated with the incidence of neutropenia. Conclusion: These findings suggest that the genetic polymorphisms of DPYD and MTHFR may be predictive factors for the occurrence of severe 5-FU-related AEs.
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| Free Research Field |
消化器外科
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