| Project/Area Number |
18K15752
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Okayama University |
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Principal Investigator |
Yasuda Yukiko 岡山大学, 医学部, 客員研究員 (80815499)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 大腸がん / SNP / RAD17 / NINEIN / NIN / 修復関連遺伝子 |
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| Outline of Final Research Achievements |
Human RAD17 acts as a signal for checkpoint activation in response to DNA damage, and its SNP, Leu546Arg, has been shown to be susceptible to colorectal cancer. We analyzed how this property affects the risk factors for EGFR and KRAS status, which are the main causative axis of colorectal cancer, and attempted to stratify them for more effective companion diagnosis of anti-EGFR antibody drugs for colorectal cancer.
We also analyzed another candidate colorectal cancer-associated gene, the centromeric-associated protein NINEIN, and found that the NINEIN Pro1111Ala polymorphism was associated with colorectal cancer risk, with particularly high odds in men with rectal cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
大腸がんに対する分子標的治療薬としては、抗EGFR抗体薬があり、RAS遺伝子検査により、その効果を予見し、適用が決められる。今回大腸がんの易罹患性に関連するRAD17およびNINEINのSNPを対象にして、EGFRの発現亢進およびKRAS変異との関連について解析した。結果、有意な関連が示されず、当初の目的である、抗EGFR抗体薬のより効果的なコンパニオン診断のための層別化はかなわなかった。しかしながら、近年拡充しつつあるin silicoデータと環境を駆使することにより、がん関連遺伝子のSNPをコンパニオン診断に役立たせる可能性は強まっており、さらなる深度の解析を試行続行中である。
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