Moderate to high doses of ionizing radiation (IR) are known to increase the risk of cancer, particularly following childhood exposure. Concerns remain regarding risks from lower doses and the role of cancer-predisposing factors (CPF; genetic disorders, immunodeficiency, mutations/variants in DNA damage detection or repair genes) on radiation-induced cancer (RIC) risk. We conducted a systematic review of evidence that CPFs modify RIC risk in young people. Searches were performed in PubMed, Scopus, Web of Science, and EMBASE for epidemiologic studies of cancer risk in humans (<25 years) with a CPF, exposed to low-moderate IR. Risk of bias was considered. Fifteen articles focusing on leukemia, lymphoma, breast, brain, and thyroid cancers were included. We found inadequate evidence that CPFs modify the risk of radiation-induced leukemia, lymphoma, brain/central nervous system, and thyroid cancers and limited evidence that BRCA mutations modify radiation-induced breast cancer risk. Heterogeneity was observed across studies regarding exposure measures, and the numbers of subjects with CPFs other than BRCA mutations were very small. Further studies with more appropriate study designs are needed to elucidate the impact of CPFs on RIC. They should focus either on populations of carriers of specific gene mutations or on common susceptible variants using polygenic risk scores.
©2022 The Authors; Published by the American Association for Cancer Research.