Apolipoprotein E Genotype and Cognitive Performance in Breast Cancer Survivors

乳腺癌幸存者的载脂蛋白 E 基因型和认知表现

• 批准号: 7278630
• 负责人: BRENT John SMALL
• 金额: $ 5.95万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7278630
• 关键词: Address; Adjuvant; Adjuvant Chemotherapy; Adverse effects; Aftercare; Alleles; Alzheimer' s Disease; Apolipoprotein E; Attention; Breast; Cancer Patient; Cancer Survivor; Cardiovascular Diseases; Characteristics; Classification; Cognition; Cognitive; Cognitive deficits; Complex; Dementia; Diagnosis; Disadvantaged; Episodic memory; Exhibits; Genetic; Genotype; Impaired cognition; Language; Life; Link; Malignant Neoplasms; Measurement; Motor; Outcome; Participant; Performance; Persons; Physiological; Public Health; Quality of life; Rate; Recording of previous events; Relative (related person); Research; Review Literature; Risk; Risk Factors; Role; Sampling; Severities; Speed; Staging; Testing; Treatment-Related Cancer; United States; Woman; cancer therapy; cardiovascular risk factor; chemotherapy; cognitive control; cognitive function; experience; genetic risk factor; healthy aging; indexing; interest; malignant breast neoplasm; psychologic; survivorship

DESCRIPTION (provided by applicant): In recent years there has been considerable interest in the e4 allele of Apolipoprotein E (APOE), a genetic risk factor for Alzheimer's disease, as a risk factor for cognitive impairment in healthy aging. Recently, there has been growing recognition that women diagnosed with early stage breast cancer may experience cognitive problems as a consequence of adjuvant chemotherapy. In addition, research suggests that the presence of the e4 allele of APOE may also convey a disadvantage to the cognitive performance of breast cancer survivors. In the current proposal we examine cross-sectional differences and longitudinal changes in the cognitive functioning of a sample of breast cancer survivors and healthy controls as a function of APOE- e4 genotype. Specifically, we will assess APOE genotype of a group of breast cancer survivors who have been examined for over 3 years since the inception of treatment, as well as a matched sample of healthy controls who have been examined at a single measurement point. The specific aims are: 1) To compare cross-sectional differences in the cognitive performance of breast cancer survivors and healthy controls as a function of APOE-e4 genotype; 2) To examine longitudinal changes in cognitive performance among breast cancer survivors as a function of APOE-e4 genotype; and 3) To examine the role of cancer treatment-related and cardiovascular disease factors in the presence and severity of APOE-e4-related changes in cognitive performance among breast cancer survivors. Cognitive performance is indexed with multiple tests of episodic memory, attention, complex cognition, motor speed, and language. We predict that relative to healthy controls, the cognitive performance of breast cancer survivors will be poorer and breast cancer survivors who are APOE-e4 positive will perform most poorly. In terms of longitudinal changes, we predict that breast cancer survivors who are APOE-e4 positive will exhibit greater declines longitudinally, relative to non-e4 carriers. The results of the current proposal are relevant to attempts to describe factors that may predispose cancer survivors to negative cognitive outcomes after treatment. Identifying factors that may increase a person's risk of cognitive impairment following treatment for cancer is a great concern to public health. In the current proposal, we examine the potential of APOE-e4 genotype, known risk factor for Alzheimer's disease, to predispose breast cancer survivors for poor cognitive outcomes.

描述（由申请人提供）：近年来，人们对载脂蛋白E（APOE）的e4等位基因（一种阿尔茨海默病的遗传风险因素）以及作为健康老龄化认知障碍的风险因素产生了相当大的兴趣。最近，人们越来越认识到，诊断为早期乳腺癌的女性可能会因辅助化疗而出现认知问题。此外，研究表明 APOE e4 等位基因的存在也可能对乳腺癌幸存者的认知表现产生不利影响。在当前的提案中，我们研究了乳腺癌幸存者和健康对照样本认知功能的横截面差异和纵向变化，作为 APOE-e4 基因型的函数。具体来说，我们将评估一组自治疗开始以来已接受检查超过 3 年的乳腺癌幸存者的 APOE 基因型，以及在单个测量点接受检查的健康对照的匹配样本。具体目标是： 1) 比较乳腺癌幸存者和健康对照者认知表现的横截面差异，作为 APOE-e4 基因型的函数； 2) 检查乳腺癌幸存者认知能力的纵向变化作为 APOE-e4 基因型的函数； 3) 研究癌症治疗相关因素和心血管疾病因素对乳腺癌幸存者认知能力中 APOE-e4 相关变化的存在及其严重程度的影响。认知表现通过情景记忆、注意力、复杂认知、运动速度和语言的多项测试来衡量。我们预测，相对于健康对照，乳腺癌幸存者的认知表现会较差，而 APOE-e4 阳性的乳腺癌幸存者表现最差。就纵向变化而言，我们预测，相对于非 e4 携带者，APOE-e4 阳性的乳腺癌幸存者将表现出更大的纵向下降。当前提案的结果与描述可能使癌症幸存者在治疗后出现负面认知结果的因素的尝试相关。确定癌症治疗后可能增加患者认知障碍风险的因素是公众健康关注的焦点。在当前的提案中，我们研究了 APOE-e4 基因型（阿尔茨海默病的已知危险因素）使乳腺癌幸存者容易出现认知结果不佳的可能性。