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J Clin Oncol. 2013 May 1;31(13):1656-61. doi: 10.1200/JCO.2012.46.2143. Epub 2013 Mar 25.

Cytokine genetic variations and fatigue among patients with breast cancer.

Author information

1
Department of Psychology, University of California, Los Angeles, CA 90095-1563, USA. jbower@ucla.edu

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

PMID:
23530106
PMCID:
PMC3635681
DOI:
10.1200/JCO.2012.46.2143
[Indexed for MEDLINE]
Free PMC Article
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