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Identification of Genetic Markers Associated With Self-Reported Attentional Function

  • Author(s): Merriman, John D.
  • Advisor(s): Miaskowski, Christine
  • et al.
Abstract

Subgroups of individuals may be at greater risk for changes in attentional function before, during, and after cancer treatment. Proposed mechanisms for these changes may include genetic predisposition to cytokine and neurotransmitter dysregulation. The purposes of this dissertation research were to identify subgroups of individuals with distinct trajectories of attentional function and to evaluate for phenotypic and genotypic (i.e., variations in cytokine and neurotransmission genes) differences among these subgroups. Self-reported attentional function was evaluated in two independent samples using the Attentional Function Index. In the first sample of 167 oncology patients receiving radiation therapy and their 85 family caregivers, three latent classes were identified using growth mixture modeling: high (15.5%), moderate-to-high (48.0%), and moderate (36.5%) attentional function. Participants in the moderate class were younger, with more comorbidities and lower functional status. Multivariable models controlled for phenotypic differences among classes, population stratification due to race/ethnicity, and other genetic variations in the same gene. A cytokine gene variation (i.e., IL6 rs1800795) remained a significant genotypic predictor of latent class membership in multivariable models. In addition, two catecholaminergic gene variations (i.e., ADRA1D rs4815675, SLC6A3 rs37022), a gamma-aminobutyric acid (GABA)-ergic gene variation (i.e., SLC6A1 rs2697138), and two serotonergic gene variations (i.e., HTR2A rs2296972, rs9534496) remained significant predictors of latent class membership. In the second sample of 397 patients with breast cancer, three latent classes were identified: high (41.6%), moderate (25.4%), and low-moderate (33.0%) attentional function. Patients in the low-moderate class were younger than those in the high class, with more comorbidities and lower functional status than the other two classes. Controlling for phenotypic differences among classes, population stratification due to race/ethnicity, and other genetic variations in the same gene, a cytokine gene variation (i.e., IL1R1 rs949963) remained a significant genotypic predictor of latent class membership. Findings provide evidence of subgroups of individuals with distinct trajectories of attentional function and of genetic associations with subgroup membership. These findings suggest that variations in genes that encode for inflammatory cytokines and for three distinct but related neurotransmission systems are involved in attentional function.

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