Identification of Genetic Markers Associated With Attentional Fatigue

描述(由申请人提供)：在要求苛刻的情况下，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。这种症状表现为在注意力需求很高的时候，集中注意力和保持有目的的活动的能力下降。大约22%的乳腺癌患者报告在治疗前存在高度的注意力疲劳。然而，关于乳腺癌治疗前、治疗中和治疗后这一症状的纵向数据很少。还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控时，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SNPs可能会影响乳腺癌女性患者注意力疲劳严重程度的个体差异。因此，这项研究的具体目标是，在乳腺癌手术前招募的女性样本中，每隔6个月每月跟踪一次：(1)确定注意力疲劳的自我评级如何随着时间的推移而变化；(2)确定哪些个人、健康、疾病和环境变量预测注意力疲劳初始水平和/或注意力疲劳轨迹的个体间差异；以及(3)确定与促炎细胞因子调节相关的特定候选基因是否有助于初始注意力疲劳水平和/或注意力疲劳轨迹的个体间差异。410名接受乳腺癌手术的女性在六个月的时间里完成了一系列仪器，包括手术前和手术后每个月的注意力功能指数(AFI)，其中318名女性提供了血样。将使用定制的SNP基因分型阵列(加利福尼亚州圣地亚哥Illumina Inc.)筛选三种致炎细胞因子(IL-1β、IL-6、TNFA)的候选基因。注意力疲劳等级和基因类型将使用G2分析、方差分析和分层线性建模(HLM)来评估，以回答本研究的具体目标。研究注意力疲劳的变化，以及注意力疲劳与基因组标志物之间的关系，可能会提供有关症状发生的潜在机制的信息，有助于识别处于最高风险的女性，并确定新的治疗靶点以减少注意力疲劳。

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.