2020 Fiscal Year Final Research Report

Analysis of gastrointestinal cancer risk-related function SNP and its clinical application

Research Project

PDF

Project/Area Number	18K08665
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Chiba Cancer Center (Research Institute)
Principal Investigator	Nakamura Yohko 千葉県がんセンター(研究所), がん予防センター, 主任上席研究員 (60260254)
Co-Investigator(Kenkyū-buntansha)	下里修千葉県がんセンター(研究所), がん予防センター腫瘍ゲノム研究室, 室長 (30344063) 巽康年千葉県がんセンター(研究所), がん予防センター腫瘍ゲノム研究室, 研究員 (00450578)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	がん / 遺伝子 / ゲノム / SNP / がん予防
Outline of Final Research Achievements	Development of the novel biomarkers to predict cancer risk is considered to be important for cancer prevention. We therefore attempted to identify non-synonymous germline single nucleotide polymorphisms (SNPs) associated with carcinogenesis by using next generation sequencing (NGS) of the cancer-related gene panel. Of 116 participants enrolled in a Japanese prospective cohort study, our NGS analysis revealed that two SNPs were recurrently observed in the participants diagnosed with colon cancer with 18.6% and 16.3% of frequencies. On the other hand, one SNP was recurrently observed in gastric cancer group with 12.5% of frequency. All of them were significantly enriched in each cancer group, when compared with cancer-free participants. Intriguingly, two of three SNPs were located in certain functional domains. Our present study strongly suggests that these SNPs are associated with carcinogenesis of certain malignancies resulting from the alteration of the function of these genes.
Free Research Field	分子生物学
Academic Significance and Societal Importance of the Research Achievements	体細胞変異の頻度が高いと評価されたがん関連遺伝子409 種類の全エクソン解析をすることで、がんリスク多型と体細胞でのがんドライバー変異、さらに遺伝子変異のパターンから変異Signature及びコピーナンバーの変異を一度に統合して解析することは、がんの遺伝子異常を推測することが可能になると考えられる。我々は、個々の患者の包括的な理解が多数のゲノム情報の組み合わせでがん予防のバイオマーカーとして確立でき、がん臨床バイオマーカー、発がん機構の解析と結びつくことで特色のある独創的なものとなると考える。この成果は、Clinical Genomicsの概念を実際のがん臨床に反映されていくものと期待される。