Investigating the causes of childhood acute lymphoblastic leukemia through mutational epidemiology.

作者：A. D. de Smith, Naying Zhou, Yun-Qi Li, Tan-Xin Liu, Nathan Patrus, Joseph L. Wiemels · 发表于：Current Problems in Pediatric and Adolescent Health Care · 年份：2025 · DOI：10.1016/j.cppeds.2025.101818 · 被引用次数：2 · 研究领域：Medicine

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and prevention of this disease would significantly reduce childhood mortality and morbidity. While the role of germline genetic variation in the etiology of ALL is well established, the contribution of modifiable risk factors is less well known. Epidemiologic studies have identified several environmental and infectious or immune-related factors associated with childhood ALL, although studies often relied on questionnaire data, which can be prone to recall bias, and/or provided limited information on the potential leukemogenic role of these exogenous exposures. Environmental exposures that have carcinogenic properties (e.g., tobacco smoke, ultraviolet radiation) can leave behind molecular footprints in tumor samples that have specific patterns of mutations, and these mutational signatures can be leveraged to study cancer etiology. Mutational epidemiology has thus emerged as a novel approach to investigate the potential carcinogenic role of exogenous exposures in cancer development, by leveraging the availability of sequencing data in large numbers of patients and combining epidemiological methods with analysis of mutational signatures, which may reveal a personalized history of causative exposures. Such studies have already yielded discoveries in adult solid tumors, identifying novel risk factors and providing insights into environmental factors that may underlie global variation in cancer incidence. How...