The rise in cancer survival rates has raised concerns about the long-term adverse effects of cancer treatment, including neurocognitive impairment. Neurocognitive deficits such as attention and processing speed are frequently observed and can have a profound, lifelong impact in daily life of cancer patients. Interestingly, large interpatient variability exists in cognitive outcomes. Emerging evidence indicates that such differences may be related to genetic variation. The aim of our review was to systematically summarize the current literature on the modulatory effects of germline genetic polymorphisms on cancer treatment-induced cognitive changes and the potential age-dependent impact in cancer survivors. The PubMed/Medline database was screened using an extensive search string focusing on four components: “cancer”, “cancer treatment”, “neurocognitive outcome” and “germline genetic variation”. Seventeen studies meeting predefined eligibility criteria were analyzed, including sixteen candidate gene studies and one genome-wide association study. 38 polymorphisms in 15 genes across proposed pathophysiological pathways, including (1) neural plasticity and repair, (2) neuroinflammation and defenses against oxidative stress, (3) neurotransmission, and (4) folate metabolism pathway, were reported to be significantly associated with treatment-related neurocognitive dysfunction or neuroimaging abnormalities. Still, some study results remained discordant, partly due to the methodological heterogeneity (i.e. in test assessments, age, cancer-type populations). Future large-scale, (epi-)genome studies integrating neurocognitive assessments and advanced neuroimaging techniques, are recommended in order to investigate neurotoxicity throughout the lifespan. Hence, adverse neurodevelopmental problems during childhood and neurodegenerative processes later in life could be minimized based on genetic risk classifications.

中文翻译：

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在整个生命周期中癌症患者神经认知发育的遗传调控：系统评价。

癌症存活率的上升引起了人们对癌症治疗的长期不利影响的担忧，包括神经认知障碍。经常观察到诸如注意力和处理速度之类的神经认知缺陷，这些缺陷会对癌症患者的日常生活产生深远的，终生的影响。有趣的是，认知结果中存在较大的患者间差异。越来越多的证据表明，这种差异可能与遗传变异有关。我们综述的目的是系统地总结有关种系遗传多态性对癌症治疗引起的认知变化以及癌症幸存者潜在的年龄依赖性影响的调节作用的现有文献。使用广泛的搜索字符串筛选了PubMed / Medline数据库，该搜索字符串着重于四个组成部分：“癌症”，“癌症治疗”，“ “神经认知结果”和“种系遗传变异”。分析了符合预定资格标准的十七项研究，包括十六项候选基因研究和一项全基因组关联研究。据报道，拟议中的病理生理学途径中有15个基因的38个多态性，包括（1）神经可塑性和修复，（2）神经炎​​症和抗氧化应激的防御，（3）神经传递和（4）叶酸代谢途径，与治疗显着相关。相关的神经认知功能障碍或神经影像异常。尽管如此，一些研究结果仍然不一致，部分是由于方法的异质性（即在测试评估，年龄，癌症类型人群中）。结合神经认知评估和先进的神经成像技术的未来大规模（epi-）基因组研究，为了研究整个生命周期的神经毒性，建议使用。因此，根据遗传风险分类，可以将儿童期和生命后期神经退行性过程中不利的神经发育问题减至最少。