Genetic predictors of fatigue in prostate cancer patients treated with androgen deprivation therapy: Preliminary findings

摘要

Background: Fatigue is a common and distressing side effect of androgen deprivation therapy (ADT) for prostate cancer. The goal of the current study was to examine the relationship between changes in fatigue following initiation of ADT and single nucleotide polymorphisms (SNPs) in three pro-inflammatory cytokine genes: interleukin-1 beta (IL1B), interleukin-6 (IL6), and tumor necrosis factor alpha (TNFA). Methods: As part of a larger study, men with prostate cancer (n=53) were recruited prior to initiation of ADT. Fatigue was assessed at recruitment and 6. months after initiation of ADT. DNA was extracted from blood drawn at baseline. Results: Patients with the IL6-174 (rs1800795) G/C or C/C genotype displayed greater increases in fatigue intrusiveness, frequency, and duration than the G/G genotype (p values ≤0.05), although inclusion of age, race, and baseline depressive symptomatology in the model attenuated these relationships (p values ≤0.09). Patients with the TNFA-308 (rs1800629) G/A genotype showed greater increases in fatigue severity than the G/G genotype (p=0.02). IL1B-511 (rs16944) genotype did not significantly predict changes in fatigue (p values >0.46). Patients with higher numbers of variants displayed greater increases in fatigue duration and interference (p values ≤0.02) than patients with lower numbers of variants. Conclusions: Prostate cancer patients treated with ADT who carry variant alleles of the IL6 and TNFA genes are susceptible to heightened fatigue. These preliminary data lend support for the role of genetic variation in the development of cancer-related fatigue secondary to ADT. Findings are relevant to attempts to develop personalized approaches to cancer treatment.