Preliminary Evidence of a Genetic Association Between Tumor Necrosis Factor Alpha and the Severity of Sleep Disturbance and Morning Fatigue

Abstract

Although fatigue and sleep disturbance are prevalent symptoms in oncology patients and their family caregivers, little is known about the factors that contribute to interindividual variability in symptom severity ratings as well as in their underlying biological mechanisms. In this study, we sought to determine whether a functional genetic variation in a prominent proinflammatory cytokine, tumor necrosis factor-alpha (TNFA-308G>A [rs1800629] promoter polymorphism) was associated with overall ratings of sleep disturbance and fatigue as well as with the trajectories of these symptoms. Over 6 months, participants completed standardized measures of sleep disturbance and fatigue. Multiple linear regression was used to assess the effect of the TNFA genotype and other covariates on mean sleep disturbance and fatigue scores. Hierarchical linear modeling was used to determine the effect of TNFA genotype on the trajectories of these symptoms. Common allele homozygotes reported higher levels of sleep disturbance (p=.09) and morning fatigue (p=.02) than minor allele carriers. Multivariate analyses demonstrated that age and genotype were predictors of both mean symptom scores and the trajectories of these symptoms. Findings provide preliminary evidence of an association between a functional promoter polymorphism in the TNFA gene and the severity of sleep disturbance and morning fatigue in oncology patients and their family caregivers.