a Unit for Psychooncology and Health Psychology, Department of Oncology, Aarhus University Hospital, and Department of Psychology and Behavioural Sciences , Aarhus University , Aarhus , Denmark.
b The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH , Copenhagen , Denmark.
Acta Oncol. 2019 May;58(5):537-547. doi: 10.1080/0284186X.2019.1578410. Epub 2019 Mar 1.
Cancer-related cognitive impairment (CRCI) is a commonly reported complaint among non-CNS cancer patients. Even subtle CRCI may have detrimental effects on quality of life and identifying patients at increased risk for CRCI to improve survivorship care is important. In the present paper, we systematically reviewed available studies of possible genetic risk factors for developing CRCI. Keyword-based systematic searches were undertaken on 24 July 2018 in PubMed, Web of Science, The Cochrane Library, and CINAHL. Three authors independently evaluated full-texts of identified papers and excluded studies with registration of reasons. Seventeen studies reporting results from 14 independent samples were included for review. Two authors independently quality assessed the included studies. The review was preregistered with PROSPERO (CRD42018107689). Ten studies investigated apolipoprotein E (APOE), with four studies reporting that carrying at least one risk allele (APOE4 (ε4)) was associated with CRCI, while six studies found no association. The remaining identified genetic risk variants associated with CRCI located in: , four DNA repair genes, five oxidative stress genes, 22 genes related to breast cancer phenotype, and . No associations were found between CRCI and genes coding for interleukin-6 (), tumor necrosis factor alpha (), interleukin 1 beta (), and brain-derived neurotropic factor (). With the exception of , the genetic risk factors had only been investigated in one or two studies each. Overall, the available evidence of possible genetic risk factors for CRCI is limited. While some research suggests a role for the ε4 allele, the literature is generally inconsistent, and the currently available evidence does not allow clear-cut conclusions regarding the role of genetic factors in the development of CRCI. Larger genetic studies and studies investigating additional genetic variants are needed to uncover genetic risk factors for CRCI.
癌症相关认知障碍（CRCI）是一种常见的非中枢神经系统癌症患者报告的抱怨。即使是轻微的 CRCI 也可能对生活质量产生不利影响，确定有发生 CRCI 风险的患者以改善生存护理非常重要。在本论文中，我们系统地回顾了可能发生 CRCI 的遗传风险因素的现有研究。2018 年 7 月 24 日，我们在 PubMed、Web of Science、The Cochrane Library 和 CINAHL 上进行了基于关键词的系统搜索。三位作者独立评估了确定论文的全文，并排除了有注册原因的研究。有 17 项研究报告了 14 个独立样本的结果，包括审查。两位作者独立评估了纳入研究的质量。该综述已在 PROSPERO（CRD42018107689）上预先注册。有 10 项研究调查了载脂蛋白 E（APOE），其中 4 项研究报告称，携带至少一个风险等位基因（APOE4（ε4））与 CRCI 相关，而 6 项研究没有发现关联。其余确定的与 CRCI 相关的遗传风险变异位于：、四个 DNA 修复基因、五个氧化应激基因、22 个与乳腺癌表型相关的基因和。在 CRCI 与编码白细胞介素-6（）、肿瘤坏死因子-α（）、白细胞介素 1β（）和脑源性神经营养因子（）的基因之间没有发现关联。除了以外，这些遗传风险因素每个都只在一项或两项研究中进行了调查。
总的来说，CRCI 可能的遗传风险因素的现有证据是有限的。虽然一些研究表明 ε4 等位基因起作用，但文献普遍不一致，目前的证据不允许对遗传因素在 CRCI 发展中的作用得出明确的结论。需要更大的遗传研究和研究调查其他遗传变异，以发现 CRCI 的遗传风险因素。
