第二恶性肿瘤（SMN）是儿童癌症幸存者（CCS）最严重的长期风险之一，显着影响患者的长期生存。虽然放疗和化疗是已知的危险因素，但观察到的个体间变异表明遗传因素会导致 SMN 风险。本文旨在对 CCS 中与 SMN 风险相关的遗传因素进行系统评价。在 PubMed、Scopus 和 Web of Sciences 中进行检索。其中包括十八项研究（十一项候选基因研究、三项全基因组关联研究和四项全外显子组/基因组测序研究）。纳入的研究基于不同类型的第一癌症，调查任何或特定类型的 SMN，并主要关注参与药物代谢和 DNA 修复途径的基因。研究设计和用于表征遗传变异的方法的这些差异限制了结果的范围，并凸显了进一步广泛和标准化研究的必要性。然而，这篇综述提供了 SMN 风险相关变异和基因的有价值的汇编，促进了有效复制并加深了我们对 CCS 这一主要风险的遗传基础的理解。

Second malignant neoplasm (SMN) is one of the most severe long-term risks for childhood cancer survivors (CCS), significantly impacting long-term patient survival. While radiotherapy and chemotherapy are known risk factors, the observed inter-individual variability suggests a genetic component contributing to the risk of SMN. This article aims to conduct a systematic review of genetic factors implicated in the SMN risk among CCS. Searches were performed in PubMed, Scopus, and Web of Sciences. Eighteen studies were included (eleven candidate gene studies, three genome-wide association studies, and four whole exome/genome sequencing studies). The included studies were based on different types of first cancers, investigated any or specific types of SMN, and focused mainly on genes involved in drug metabolism and DNA repair pathways. These differences in study design and methods used to characterize genetic variants limit the scope of the results and highlight the need for further extensive and standardized investigations. However, this review provides a valuable compilation of SMN risk-associated variants and genes, facilitating efficient replication and advancing our understanding of the genetic basis for this major risk for CCS.