Management of hereditary endometrial cancer based on molecular genetic analysis and clinical features

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Akita University
• Principal Investigator: Sato Naoki 秋田大学, 医学系研究科, 非常勤講師 (40447199)
• Co-Investigator(Kenkyū-buntansha): 菅原 多恵 秋田大学, 医学部附属病院, 助教 (40566163) ; 金子 恵菜実 秋田大学, 医学部附属病院, 医員 (70838713)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 遺伝子子宮体癌 / リンチ症候群 / スクリーニング / 遺伝学的検査 / サーベイランス

Outline of Final Research Achievements

Lynch syndrome (LS) is caused by a germline mutation in the DNA mismatch repair (MMR) genes, and thus the cancer risk of LS is inherited in an autosomal dominant pattern. Performing molecular analyses on the tumors of endometrial cancer (EC)patients, we selected “suspected LS” as the candidates for genetic analyses. Genetic testing was performed to the candidates. We compared our proprietary screening strategy with other strategies to verify the cost effectiveness. We analyzed the risk factors for each LS-associated cancer. We examined the benefits and the timing of adaptation of preventive risk reduction for women with LS. We revealed the features of“MLH1 promoter hypermethylation ” and “suspected-LS” in EC with MMR- deficiency. his result was reported to Journal of Gynegology Oncology. Based on research results, latest knowledge and clinical information, we are currently creating a dissertation of LS identification methods and practical management guidelines in EC.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

若年発癌・多発癌・家系内集積がLSの典型で、発症者は社会活動からの離脱を余儀なくされる。LS保因者のリスクは多様であり、変異遺伝子、変異部位・様式、年齢、家系・地域性を含む環境因子などによって各関連癌発生リスクも異なる。LSの効率的な識別法と適切な管理指針の構築によって、後続関連癌の発生予防や早期発見を導き、血縁者にも遺伝性評価と予防的医療を提案する機会となる。LS保因者に対する予知的検診、予防医療、個別化治療の未来展開は、社会保障費と人的損失を全体として削減する。