| Project/Area Number |
18K09158
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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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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西山 博之 筑波大学, 医学医療系, 教授 (20324642)
河原 貴史 筑波大学, 医学医療系, 講師 (50758919)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 尿路上皮癌 / 遺伝子変異 / 遺伝要因 / 環境要因 / ctDNA / SNP / cfDNA / 膀胱癌 / 体細胞変異 / 分子基盤 / 変異 / 一塩基多型 |
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| Outline of Final Research Achievements |
The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer. Germline TP53 codon 72 polymorphism and somatic mutations of 50 cancer-associated genes were analyzed. The allele frequency of TP53 codon 72 in our cohort was 37, 42, and 21% for Arg/Arg, Arg/Pro, and Pro/Pro, respectively. Interestingly, the prevalence of FGFR3 mutation was higher in patients with the Arg allele, whereas that of the RAS mutation was higher in patients without the Arg allele. The same association was seen in non-muscle-invasive bladder cancer (NMIBC) patients and no differences were observed in muscle-invasive bladder cancer patients. The germline TP53 codon 72 polymorphism was associated with mutations of FGFR3 or RAS and expression of FGFR1 and FGFR3 in NMIBC. These findings provide new insight into the molecular mechanisms underlying the influence of the genetic background on carcinogenesis in bladder cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
がんの発生や進展は、遺伝子変異が蓄積することにより起こるとされているが、特定の遺伝子に変異が起こる機序については明らかになっていない。本研究では、患者の持つTP53の遺伝子多型であるTP53 codon72のアレル型が、特定の体細胞遺伝子変異に関わることを明らかにした。遺伝子プロファイルに基づいて個々の患者の最適な治療選択を行う場合には、がん細胞自身の遺伝子変異の解析に加えて、患者の遺伝的な素因も考慮して行うことが示唆された。
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