Identification of susceptibility genes to elucidate the pathogenesis of drug-induced hearing loss.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09743
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: MORIMOTO NORIKO 国立研究開発法人国立成育医療研究センター, 小児外科系専門診療部, 診療部長 (40286555)
• Co-Investigator(Kenkyū-buntansha): 要 匡 国立研究開発法人国立成育医療研究センター, ゲノム医療研究部, 部長 (40264288) ; 柳 久美子 国立研究開発法人国立成育医療研究センター, ゲノム医療研究部, 研究員 (90294701)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 薬剤感受性遺伝子 / シスプラチン難聴

Outline of Final Research Achievements

The purpose of this study was to investigate the etiology of hearing loss caused by platinum agents, which are widely used in the treatment of pediatric solid tumors. Hearing loss varied among individuals even when platinum drugs were used under the same conditions, and we hypothesized that the cause of hearing loss might be related to genetic polymorphisms. We analyzed the use of platinum drugs, the presence or absence of hearing loss induction, and the presence of drug susceptibility polymorphisms (TPMT, COMR, ACYP2) reported in other countries. Among 123 pediatric patients, TPMT was found in 4 patients (with hearing loss) and ACYP2 in 6 patients (2 with hearing loss), and the logistic regression analysis model suggested that gene polymorphism + drug dosage + younger age were most associated with hearing loss.

Free Research Field

小児難聴

Academic Significance and Societal Importance of the Research Achievements

近年は化学療法後の生存率も高くなり、治癒後の社会生活を豊かに過ごすことが求められているものの、白金製剤による難聴のために生活に支障をきたすことも少なくない。難聴の程度にも個人差が明らかであるため、本研究では難聴の原因が遺伝子多型に関連するのではないかと考えた。結果として遺伝子多型があり、低年齢で薬剤投与量も多かった場合に難聴の危険性が高まることが明らかになった。この結果は将来を見据えて、治療として化学療法の選択をする際に資するものと考える。