Diabetes in childhood cancer survivors: emerging concepts in pathophysiology and future directions.
Diabetes in childhood cancer survivors: emerging concepts in pathophysiology and future directions.
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DOI：
10.3389/fmed.2023.1206071
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发表时间：
2023
影响因子：
3.9
通讯作者：
Mostoufi-Moab, Sogol
中科院分区：
文献类型：
--
作者：
Bhandari, Rusha;Armenian, Saro H.;Mccormack, Shana;Natarajan, Rama;Mostoufi-Moab, Sogol
随着癌症治疗和支持性护理的进步，越来越多的儿童癌症幸存者面临着与年轻时接受癌症治疗相关的合并症的沉重负担。尽管在过去几十年里，儿童癌症幸存者大多数慢性健康状况的发病率总体有所下降，但某些后期影响，特别是糖尿病（DM）的累积发病率却有所增加。其意义重大，因为糖尿病是心血管疾病的一个关键危险因素，而心血管疾病是儿童癌症幸存者过早死亡的主要原因。癌症幸存者 DM 的潜在病理生理学是多因素的。与对照组相比，幸存者患糖尿病的年龄更小，这可能反映了这些个体的“加速衰老”表型。增加儿童癌症幸存者患糖尿病风险的治疗相关暴露（即化疗、放疗）可能与已确定的糖尿病风险因素（例如年龄较大、肥胖、种族和民族）相加。新兴研究还指出了与衰老和癌症治疗相关的糖尿病相关的细胞过程的相似之处。尽管如此，糖尿病风险仍然存在明显的个体差异，这不能仅用人口和治疗风险因素来解释。最近的研究强调了生殖系遗传风险因素和表观遗传修饰的作用，这些因素与普通人群和肿瘤人群中的 DM 风险相关。这篇综述总结了我们目前对儿童癌症幸存者中公认的糖尿病危险因素的理解，以帮助为疾病筛查、预防和治疗的有针对性的方法提供信息。此外，它强调了在理解个体治疗暴露的相对贡献以及它们发挥作用的机制方面现有的科学差距，这些作用使该人群在癌症治疗后独特地容易患上糖尿病。
With advancements in cancer treatment and supportive care, there is a growing population of childhood cancer survivors who experience a substantial burden of comorbidities related to having received cancer treatment at a young age. Despite an overall reduction in the incidence of most chronic health conditions in childhood cancer survivors over the past several decades, the cumulative incidence of certain late effects, in particular diabetes mellitus (DM), has increased. The implications are significant, because DM is a key risk factor for cardiovascular disease, a leading cause of premature death in childhood cancer survivors. The underlying pathophysiology of DM in cancer survivors is multifactorial. DM develops at younger ages in survivors compared to controls, which may reflect an “accelerated aging” phenotype in these individuals. The treatment-related exposures (i.e., chemotherapy, radiation) that increase risk for DM in childhood cancer survivors may be more than additive with established DM risk factors (e.g., older age, obesity, race, and ethnicity). Emerging research also points to parallels in cellular processes implicated in aging- and cancer treatment-related DM. Still, there remains marked inter-individual variability regarding risk of DM that is not explained by demographic and therapeutic risk factors alone. Recent studies have highlighted the role of germline genetic risk factors and epigenetic modifications that are associated with risk of DM in both the general and oncology populations. This review summarizes our current understanding of recognized risk factors for DM in childhood cancer survivors to help inform targeted approaches for disease screening, prevention, and treatment. Furthermore, it highlights the existing scientific gaps in understanding the relative contributions of individual therapeutic exposures and the mechanisms by which they exert their effects that uniquely predispose this population to DM following cancer treatment.
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