Impact of TNF-α (rs1800629) and IL-6 (rs1800795) Polymorphisms on Cognitive Impairment in Asian Breast Cancer Patients.
Impact of TNF-α (rs1800629) and IL-6 (rs1800795) Polymorphisms on Cognitive Impairment in Asian Breast Cancer Patients.
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DOI：
10.1371/journal.pone.0164204
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chan A
中科院分区：
文献类型：
--
作者：
Chae JW;Ng T;Yeo HL;Shwe M;Gan YX;Ho HK;Chan A
促炎性细胞因子基因启动子区的单核苷酸多态性（SNP）影响促炎性细胞因子的表达，并且细胞因子与化疗后认知损害的发生相关。因此，本研究的目的是评估亚洲早期乳腺癌患者中两种常见的促炎细胞因子基因多态性，即IL 6 -174（rs 1800795 G>C）和TNF-308（rs 1800629 G>A）与化疗相关认知障碍（CACI）之间的关联。此外，还评估了这些SNP对血浆IL-6和TNF-α水平的差异效应，以及血浆IL-6和TNF-α水平与CACI的相关性。从新加坡的两个癌症中心前瞻性招募接受化疗的亚洲早期乳腺癌患者（I期至III期）。使用经验证的FACT-Cog（版本）纵向评估患者的认知功能。3)和客观计算机化组合，Headminder™。采用多重免疫分析法分析血浆IL-6和TNF-α水平，并采用桑格测序法进行基因分型。采用回归分析和广义估计方程进行统计分析。共纳入125例患者（平均年龄：50.3岁;中国人：80.8%;绝经后：48.0%; 68.0%接受了基于蒽环类药物的化疗）。36.8%的患者经历过自我感知的认知障碍，主要表现在记忆（32.8%）和注意力（34.2%）领域。焦虑（p<0.001）和失眠（p = 0.003）水平较高的患者也报告了更多的自我感知认知障碍。较高的IL-6血浆浓度与自我感知的认知障碍的严重程度相关（p = 0.001）。细胞因子基因多态性与血浆细胞因子的表达无关。目前的研究结果进一步有助于越来越多的证据支持促炎细胞因子IL-6在化疗后认知障碍发生中的作用。然而，这些细胞因子的遗传多态性在该队列中的细胞因子波动以及认知障碍中没有发挥主要作用。随着越来越多的证据支持细胞因子假说，未来的研究应该调查抗炎药在减轻化疗相关的认知障碍中的作用。
Expression of pro-inflammatory cytokines is influenced by single nucleotide polymorphisms (SNPs) in the promoter regions of the pro-inflammatory cytokine genes, and cytokines are associated with the occurrence of post-chemotherapy cognitive impairment. Hence, the aim of this study was to evaluate the associations between two common pro-inflammatory cytokine gene polymorphisms namely, IL6-174 (rs1800795 G>C) and TNF-308 (rs1800629 G>A), and chemotherapy-associated cognitive impairment (CACI) among Asian early-stage breast cancer patients. In addition, the differential effect of these SNPs on plasma IL-6 and TNF-α levels, and the associations of plasma IL-6 and TNF-α levels with CACI were also assessed. Asian early-stage breast cancer patients (Stage I to III) receiving chemotherapy were prospectively recruited from two cancer centers in Singapore. Patients' cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) and an objective computerized battery, Headminder™ at three-time points. Plasma IL-6 and TNF-α levels were analyzed using the multiplex immunoassay, and genotyping was performed using Sanger sequencing. Regression analyses and generalized estimating equation were utilized for statistical analysis. A total of 125 patients were included (mean age: 50.3; Chinese: 80.8%; post-menopausal: 48.0%; 68.0% received anthracycline-based chemotherapy). 36.8% patients experienced self-perceived cognitive impairment, detected in memory (32.8%) and attention (34.2%) domains. Patients with higher levels of anxiety (p<0.001) and insomnia (p = 0.003) also reported more self-perceived cognitive impairment. Higher plasma concentrations of IL-6 were associated with greater severity of self-perceived cognitive impairment (p = 0.001). Polymorphisms of cytokine genes were not associated with expression of plasma cytokines. Present findings further contribute to the growing evidence that supports the role of the pro-inflammatory cytokine IL-6 in the occurrence of cognitive impairment post-chemotherapy. However, genetic polymorphism of these cytokines did not play a major role to the cytokine fluctuations as well as cognitive impairment in this cohort. With an increasing evidence to support the cytokine hypothesis, future studies should investigate the role of anti-inflammatory agents in mitigating the cognitive impairment associated with chemotherapy.
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影响因子：
45.3
作者：
Bower, Julienne E.;Ganz, Patricia A.;Cole, Steven W.
通讯作者：
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影响因子：
--
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作者：
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