Identification of Genetic Markers Associated With Attentional Fatigue

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DESCRIPTION (provided by applicant): The direction of attention (i.e., purposeful concentration) during demanding situations, like the diagnosis and treatment of breast cancer, results in attentional fatigue. This symptom is experienced as a decreased ability to concentrate and to maintain purposeful activity at a time when attentional demands are high. Approximately 22% of women with breast cancer report high levels of attentional fatigue before treatment. However, very little longitudinal data are available on this symptom before, during, and after breast cancer treatment. No studies have attempted to link genetic markers with the severity or trajectories of self-reported attentional fatigue. Cognitive changes, including attentional fatigue, may occur when the production of proinflammatory cytokines is disregulated. Therefore, it is possible that SNPs in the genes that code for proinflammatory cytokines influence inter-individual differences in the severity of attentional fatigue in women with breast cancer. Therefore, the specific aims of this study, in a sample of women who were recruited prior to surgery for breast cancer and were followed at monthly intervals for six months, are to: (1) determine how self-ratings of attentional fatigue change over time; (2) determine which personal, health and illness, and environmental variables predict inter-individual differences in initial levels of attentional fatigue and/or the trajectories of attentional fatigue; and (3) determine whether specific candidate genes associated with proinflammatory cytokine regulation contribute to inter-individual differences in initial levels of attentional fatigue and/or the trajectories of attentional fatigue. Four hundred ten women who underwent surgery for breast cancer completed a number of instruments that included the Attentional Function Index (AFI) before surgery and each month after surgery for six months, and 318 of these women provided blood samples. Candidate genes for three proinflammatory cytokines (IL-1beta, IL-6, TNFA) will be screened using a custom SNP genotyping array (Illumina Inc., San Diego, CA). Attentional fatigue ratings and genotypes will be evaluated using G2 analyses, analysis of variance, and hierarchical linear modeling (HLM) to answer the specific aims of this study. An investigation of changes in attentional fatigue, as well as the associations between attentional fatigue and genomic markers, may provide information about potential mechanisms that underlie the development of the symptom, lead to the identification of women at greatest risk, and identify new therapeutic targets to decrease attentional fatigue. PUBLIC HEALTH RELEVANCE: The American Cancer Society estimates that 254,650 women were diagnosed with breast cancer in 2009. For women with breast cancer, attentional fatigue may be experienced as difficulty concentrating and completing tasks when there are many competing demands. This study, which examines patient characteristics and genetic (inherited) factors that contribute to attentional fatigue, may provide information about the causes of this symptom, which women are at greatest risk, and identify new treatment approaches to be used to decrease attentional fatigue.