Branched-chain amino acid level and cancer: Mendelian Randomization Study

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19473
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58030:Hygiene and public health-related: excluding laboratory approach
• Research Institution: National Cancer Center Japan
• Principal Investigator: Katagiri Ryoko 国立研究開発法人国立がん研究センター, がん対策研究所, 室長 (60813508)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: メンデルランダム化解析 / 疫学 / 分岐鎖アミノ酸

Outline of Final Research Achievements

We aimed to examine the association of three branched-chain amino acids with health outcomes using a Mendelian Randomization approach, in which genetic information is used to adjust for unknown and unobserved confounding effects. Single nucleotide polymorphisms (SNPs as instrumental variables) associated with branched-chain amino acids were extracted from previous reports. The estimates were obtained from genome-wide association analysis (GWAS) of branched-chain amino acids in the Japanese population. In addition, although pancreatic cancer was initially assumed to examine as health outcome, the enough sample size could not be collected, so the study was changed to examine colorectal cancer. However, using the results of GWAS, the estimation of variance explained by selected SNPs would be low, making it difficult to interpret the results of MR analysis. As a result, I concluded that MR analysis would be difficult within the framework of this study.

Free Research Field

栄養疫学

Academic Significance and Societal Importance of the Research Achievements

分岐鎖アミノ酸と糖尿病の関連が知られる中、疫学研究からがんとの関連の報告もあり、未観察交絡の影響を調整して関連の検討を行うメンデル無作為化解析は、分岐鎖アミノ酸とがん、特に糖尿病などの影響を調整することが難しい膵がんなどで有用であると考え研究を設定した。しかし、代謝物に対するGWAS解析の報告は、解析時点で少なく今回の手法では遺伝的な説明率が低くなり、メンデルランダム化解析の実施は難しいということが判明した。今後の代謝物に関するゲノム研究の増加や、罹患率の低いがんの研究を統合した研究プラットフォームの充実などが求められる。