2019 Fiscal Year Final Research Report

Clinical significance of pathogenic germline BRCA1/2 mutations in gastric cancer

Research Project

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Project/Area Number	17K10580
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Digestive surgery
Research Institution	Niigata University
Principal Investigator	Takizawa Kazuyasu 新潟大学, 医歯学総合病院, 助教 (30706437)
Co-Investigator(Kenkyū-buntansha)	若井俊文新潟大学, 医歯学系, 教授 (50372470) 羽入隆晃新潟大学, 医歯学総合病院, 助教 (50719705) 市川寛新潟大学, 医歯学系, 助教 (50721875) 田澤立之新潟大学, 医歯学総合病院, 准教授 (70301041) 中田光新潟大学, 医歯学総合病院, 教授 (80207802) 小杉伸一新潟大学, 医歯学総合病院, 特任教授 (90401736)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	胃癌 / BRCA / ゲノムシーケンス / 化学療法
Outline of Final Research Achievements	Defective homologous recombination (HR) due to genetic aberrations of HR genes, such as BRCA1/2 contributes to a high response of platinum therapy. Hereditary breast and ovarian cancer is one of the best described inherited cancer pre-disposition syndromes, caused by pathogenic germline BRCA1 or BRCA2 (BRCA1/2) mutations. The aim of this study is to clarify the clinical significance of defective HR in platinum-based chemotherapy for gastric cancer (GC). BRCA2 mutation contributes to favorable patient outcome after surgery in GC. In this study, some of BRCA1/2-mutated GC have high sensitivity to platinum chemotherapy. BRCA1/2 mutations may predispose to familial GC. BRCA1/2 genetic testing in patients with GC with a familial component may help to optimize medical care, including cancer surveillance and the selection of treatment modalities in the era of precision medicine.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	胃癌におけるBRCA1/2遺伝子異常の臨床的意義については未だに未解明である。本研究では、胃癌におけるBRCA1/2遺伝子異常の臨床的意義について、治療効果や予後だけでなく罹患にも関与している可能性を示した。本研究は胃癌におけるBRCA1/2遺伝子異常に着目した個別化治療の発展の科学的基盤となる可能性が示唆された。また、BRCA1/2変異は胃癌の家族集積性の原因となる可能性が示唆され、胃癌サーベイランスの最適化に寄与する可能性がある。