| Project/Area Number |
25462624
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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 |
Obstetrics and gynecology
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| Research Institution | National Center for Global Health and Medicine (2015-2016)
National Institute of Infectious Diseases (2013) |
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Principal Investigator |
Takeuchi Fumihiko 国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (50384152)
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| Co-Investigator(Kenkyū-buntansha) |
柊元 巌 国立感染症研究所, 病原体ゲノム解析研究センター, 室長 (70291127)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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| Keywords | ゲノムワイド関連解析 / 子宮頸癌 / 婦人科腫瘍学 / メタ解析 / 国際情報交換 |
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| Outline of Final Research Achievements |
Epidemiological studies suggested that cervical cancer susceptibility is heritable, but actual causal genes in human were unknown. The objective of this study was to identify cervical cancer susceptibility genes by genome-wide association study (GWAS). Collaborating with other East Asian cervical cancer cohorts, we performed GWAS involving 2609 cases and 4712 controls, followed up by testing 1461 cases and 3295 controls. We identified significant associations at 5q14 and 7p11. In our functional studies, ARRDC3 knockdown in HeLa cells caused significant reductions in susceptibility to HPV16 pseudovirion infection. This finding is an important step towards elucidating disease etiology and developing treatment of cervical cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮頸癌により全世界で年間266,000名が亡くなっており、女性の生涯リスクは0.8%である。子宮頸癌発症にヒトの遺伝的要因があることは、疫学的に示唆されていたが、どの遺伝子がその要因を担っているか未解明であった。本研究は、ヒトゲノム全体にわたって子宮頸癌発症遺伝子を探索する研究として、東アジア人で最大規模であり、新たに2箇所の遺伝子座を同定できた。この発見は、子宮頸癌の発症機序解明・治療法開発を進めるための重要な一歩となる。
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