Abstract:
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.
摘要:
已知中等至高剂量的电离辐射(IR)会增加患癌症的风险,特别是在童年暴露之后。关于低剂量的风险和癌症易感因素(CPF;遗传性疾病,免疫缺陷,DNA损伤检测或修复基因中的突变/变异)对辐射诱导的癌症(RIC)风险的影响。我们对CPF改变年轻人RIC风险的证据进行了系统评价。在PubMed中进行搜索,Scopus,WebofScience,和EMBASE用于CPF的人类癌症风险流行病学研究(25年),暴露于低-中度IR。考虑了偏倚风险。15篇关注白血病的文章,淋巴瘤乳房,大脑,甲状腺癌也包括在内。我们发现,没有足够的证据表明CPFs可以改变辐射诱导的白血病的风险,淋巴瘤大脑/中枢神经系统,和甲状腺癌和有限的证据表明BRCA突变改变辐射诱导的乳腺癌风险。在有关暴露措施的研究中观察到异质性,并且具有BRCA突变以外的CPFs的受试者数量很少。需要更适当的研究设计的进一步研究来阐明CPFs对RIC的影响。他们应该关注特定基因突变的携带者群体或使用多基因风险评分的常见易感变体。