Analyses of effects of variants with uncertain significance in the cancer related genes on the carcinogenesis in general population

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center (2018-2020); Tohoku University (2017)
• Principal Investigator: Yasuda Jun 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん制御研究部, 部長 (00281684)
• Co-Investigator(Kenkyū-buntansha): 齋藤 さかえ 東北大学, 東北メディカル・メガバンク機構, 講師 (20335491)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: がん素因遺伝子 / VUS / 前向きゲノムコホート / 家族性乳がん卵巣がん症候群

Outline of Final Research Achievements

We investigated moderately morbid VUS of familial tumor-associated genes based on Tohoku University's Japanese whole genome reference panel data to see whether they indicate an accumulation of history of malignancy and family history of malignancy based on the questionnaire information. We examined BRCA1/2, the causative gene of hereditary breast and ovarian cancer syndromes, which is included in the Japanese standard genome panel 3.5KJPNv2, and established the conditions for moderately pathological mutations (CADD>25, Eigen>0.5, MAF<0.0005). Furthermore, we compared the results with those of 35,000 participants' past and family history data collected by the Tohoku Medical Megabank Project and found that the incidence of cancer in sisters of the cohort with these moderately pathological mutations was statistically significantly higher than that of their counterparts, which was reported in a European peer-reviewed journal.

Free Research Field

腫瘍遺伝学

Academic Significance and Societal Importance of the Research Achievements

家族性腫瘍関連遺伝子の中等度に病的なVUSの腫瘍発症への寄与が統計学的に検出可能であることを示したのは前向きゲノムコホートが研究上有用であることを示した。また、こうした腫瘍関連遺伝子の中等度の病的変異を持つ個人にとってがんの発症予防や早期の検診受診などで直接利益が生まれる可能性がある。今後こうした中等度の病的変異をリスク要因として組み込んだ精密医療の確立に大きく資する研究成果と考えられる。