Cytokine genetic variations and fatigue among patients with breast cancer.
|Title||Cytokine genetic variations and fatigue among patients with breast cancer.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Bower JE, Ganz PA, Irwin MR, Castellon S, Arevalo J, Cole SW|
|Journal||J Clin Oncol|
|Date Published||2013 May 1|
|Keywords||Adult, Aged, Breast Neoplasms, Cytokines, Fatigue, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Middle Aged, Neoplasm Staging, Polymorphism, Single Nucleotide|
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.
|Alternate Journal||J. Clin. Oncol.|
|PubMed Central ID||PMC3635681|
|Grant List||P30 AG028748 / AG / NIA NIH HHS / United States |
P30-AG028748 / AG / NIA NIH HHS / United States
R01-AG026364 / AG / NIA NIH HHS / United States
R01-AG034588 / AG / NIA NIH HHS / United States
R01-CA109650 / CA / NCI NIH HHS / United States
R01-CA116778 / CA / NCI NIH HHS / United States
R01-DA032922-01 / DA / NIDA NIH HHS / United States
R01-HL095799 / HL / NHLBI NIH HHS / United States