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Cytokine genetic variations and fatigue among patients with breast cancer.

ABSTRACT: Fatigue 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.Women 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.The 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).These 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.

SUBMITTER: Bower JE

PROVIDER: S-EPMC3635681 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Cytokine genetic variations and fatigue among patients with breast cancer.

Bower Julienne E JE Ganz Patricia A PA Irwin Michael R MR Castellon Steven S Arevalo Jesusa J Cole Steven W SW

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130325 13

<h4>Purpose</h4>Fatigue 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.<h4>Patients and methods</h4>Women diagnosed with early-st ...[more]

PMID: 23530106

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Project description:PurposeThe randomized controlled OptiTrain trial showed beneficial effects on fatigue after a 16-wk exercise intervention in patients with breast cancer undergoing adjuvant chemotherapy. We hypothesize that exercise alters systemic inflammation and that this partially mediates the beneficial effects of exercise on fatigue.MethodsTwo hundred and forty women scheduled for chemotherapy were randomized to 16 wk of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). In the current mechanistic analyses, we included all participants with >60% attendance and a random selection of controls (RT-HIIT = 30, AT-HIIT = 27, UC = 29). Fatigue (Piper Fatigue Scale) and 92 markers (e.g., interleukin-6 [IL-6] and tumor necrosis factor ? [TNF-?]) were assessed at baseline and postintervention. Mediation analyses were conducted to explore whether changes in inflammation markers mediated the effect of exercise on fatigue.ResultsOverall, chemotherapy led to an increase in inflammation. The increases in IL-6 (pleiotropic cytokine) and CD8a (T-cell surface glycoprotein) were however significantly less pronounced after RT-HIIT compared with UC (-0.47, 95% confidence interval = -0.87 to -0.07, and -0.28, 95% confidence interval = -0.57 to 0.004, respectively). Changes in IL-6 and CD8a significantly mediated the exercise effects on both general and physical fatigue by 32.0% and 27.7%, and 31.2% and 26.4%, respectively. No significant between-group differences in inflammatory markers at 16 wk were found between AT-HIIT and UC.ConclusionsThis study is the first showing that supervised RT-HIIT partially counteracted the increase in inflammation during chemotherapy, i.e., IL-6 and soluble CD8a, which resulted in lower fatigue levels postintervention. Exercise, including both resistance and high-intensity aerobic training, might be put forward as an effective treatment to reduce chemotherapy-induced inflammation and subsequent fatigue.

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Cytokine genetic variations and fatigue among patients with breast cancer.

Publications

Cytokine genetic variations and fatigue among patients with breast cancer.

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