Janghee Woo, Tingting Zhai, Fang Yang, Huilei Xu, Margaret L. Healey, Denise P. Yates, Michael T. Beste, David P. Steensma
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引用次数: 0
Abstract
Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased pro-inflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS, NCT01327846) evaluated the neutralizing anti-IL-1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab vs those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL-1β blockade cooperating with CH mutations to modify the disease course.
期刊介绍:
Cancer Prevention Research publishes original studies, reviews, and perspectives in the field of cancer prevention. Its scope includes the molecular and cellular biology of premalignancy and early lesions; genetic and environmental risk factors; risk assessment and reduction; early detection research (cancer screening and diagnosis); and preventive interventions (chemoprevention, immunoprevention, and others) to intercept cancer development at early stages prior to initiation, promotion, or progression. The journal comprises preclinical, clinical, and translational research, with special attention given to molecular discoveries and an emphasis on building a translational bridge between the basic and clinical sciences.