Identification of Genetic Markers Associated With Attentional Fatigue

描述（由申请人提供）：在要求很高的情况下，如乳腺癌的诊断和治疗，注意力的方向（即有目的的集中）会导致注意力疲劳。这种症状表现为当注意力要求很高时，注意力集中和维持有目的活动的能力下降。大约22%的乳腺癌患者在治疗前报告有高度的注意力疲劳。然而，在乳腺癌治疗之前、期间和之后，很少有关于这种症状的纵向数据。没有研究试图将遗传标记与自我报告的注意力疲劳的严重程度或轨迹联系起来。当促炎细胞因子的产生失调时，可能会发生认知变化，包括注意力疲劳。因此，编码促炎细胞因子的基因中的snp可能影响乳腺癌女性注意力疲劳严重程度的个体间差异。因此，本研究的具体目的是，在乳腺癌手术前招募的女性样本中，每月随访六个月，(1)确定注意力疲劳的自我评分如何随时间变化；(2)确定哪些个人、健康和疾病以及环境变量可以预测注意疲劳初始水平和/或注意疲劳轨迹的个体间差异；(3)确定与促炎细胞因子调节相关的特定候选基因是否导致了注意疲劳初始水平和/或注意疲劳轨迹的个体间差异。410名接受乳腺癌手术的女性在手术前和术后6个月内完成了包括注意力功能指数（AFI）在内的一系列测试，其中318名女性提供了血液样本。将使用定制的SNP基因分型阵列（Illumina Inc., San Diego， CA）筛选三种促炎细胞因子（il -1 β, IL-6， TNFA）的候选基因。注意力疲劳评分和基因型将使用G2分析、方差分析和层次线性模型（HLM）来评估，以回答本研究的具体目的。对注意力疲劳变化的调查，以及注意力疲劳与基因组标记之间的关联，可能会提供关于症状发展的潜在机制的信息，导致识别风险最大的女性，并确定新的治疗靶点来减少注意力疲劳。

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.