Cytokine Genetic Variations and Fatigue Among Patients With Breast Cancer
Cytokine Genetic Variations and Fatigue Among Patients With Breast Cancer
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DOI：
10.1200/jco.2012.46.2143
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发表时间：
2013-05-01
影响因子：
45.3
通讯作者：
Cole, Steven W.
中科院分区：
文献类型：
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作者：
Bower, Julienne E.;Ganz, Patricia A.;Cole, Steven W.
疲劳是癌症治疗的常见副作用，可能在治疗结束后持续数年。然而，治疗后疲劳的风险因素尚未确定。在提示疲劳的炎症基础的研究的基础上，本研究检验了促炎细胞因子基因的表达调节多态性将预测乳腺癌幸存者治疗后疲劳的假设。患者和方法诊断为早期乳腺癌的妇女（n = 171）完成问卷调查，以评估疲劳和其他行为症状（即抑郁症状，记忆投诉，睡眠障碍），并在主要治疗后3个月内提供血液进行基因分型。从外周血白细胞中提取基因组DNA，并分析三种细胞因子基因启动子区的单核苷酸多态性（SNP）：ILB-511 C>T（rs 16944）、IL-6 - 174 G > C（rs 1800795）和TNF-308 G > A（rs 1800629）。一个添加剂的遗传风险评分计算通过总结所有三个polymorphism.ResultsThe遗传风险指数的高表达等位基因（零，一，或两个）的数量与疲劳显着相关;随着高表达等位基因的数量增加，自我报告的疲劳严重程度（P = .002）。对单个SNP的分析显示，TNF-308和IL-6 - 174与疲劳独立相关（P = 0.032）。遗传风险指数还与抑郁症状（P = 0.007）和记忆投诉（P = 0.016）相关。结论这些发现进一步暗示炎症过程是癌症相关疲劳的促成因素，并提出了一种新的策略，用于识别和治疗有这种症状风险的患者基于促炎细胞因子基因的遗传变异。J Clin Oncol 31：1656-1661. (C)2013年美国临床肿瘤学会
PurposeFatigue is a common adverse effect of cancer treatment and may persist for years after treatment completion. However, risk factors for post-treatment fatigue have not been determined. On the basis of studies suggesting an inflammatory basis for fatigue, this study tested the hypothesis that expression-regulating polymorphisms in proinflammatory cytokine genes would predict post-treatment fatigue in breast cancer survivors.Patients and MethodsWomen diagnosed with early-stage breast cancer (n = 171) completed questionnaires to assess fatigue and other behavioral symptoms (ie, depressive symptoms, memory complaints, sleep disturbance) and provided blood for genotyping within 3 months after primary treatment. Genomic DNA was extracted from peripheral-blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in the promoter regions of three cytokine genes: ILB -511 C>T (rs16944), IL6 -174 G > C (rs1800795), and TNF -308 G > A (rs1800629). An additive genetic risk score was computed by summing the number of high-expression alleles (zero, one, or two) across all three polymorphisms.ResultsThe genetic risk index was significantly associated with fatigue; as the number of high-expression alleles increased, so did self-reported fatigue severity (P = .002). Analyses of individual SNPs showed that TNF -308 and IL6 - 174 were independently associated with fatigue (P = .032). The genetic risk index was also associated with depressive symptoms (P = .007) and memory complaints (P = .016).ConclusionThese findings further implicate inflammatory processes as contributors to cancer-related fatigue and suggest a new strategy for identifying and treating patients at risk for this symptom based on genetic variants in proinflammatory cytokine genes. J Clin Oncol 31: 1656-1661. (C) 2013 by American Society of Clinical Oncology