MULTIPLE RISKS, DECISIONS & BEHAVIORS IN THE GENOMIC ERA

描述（由申请人提供）：本提案旨在为Karen Hurley博士提供高级培训和指导研究，使其成为遗传性癌症风险的独立行为研究者。它解决了基因组革命带来的两个挑战：1)在同一个人中考虑多个相互关联的降低风险的行为结果，以及2)考虑预测变量和行为结果之间关系的个体差异。遗传综合征通常会同时给几个器官带来风险，但研究通常一次评估一种筛查结果。同样，社会心理因素经常作为独立的预测因素进行分析；然而，在一个特定的人身上，他们是相互依存的。开发新的评估和统计策略，以了解患者如何处理复杂信息，并分析相互关联的行为结果，将提高研究结果的准确性和临床实用性。研究1将评估HNPCC患者对综合多器官筛查指南的纵向依从性（全部、部分或无）。聚类分析将产生感知/风险担忧类型的分类（例如，对一种癌症的选择性担忧与普遍担忧），这将用于预测随时间推移的坚持轨迹。在研究2中，BRCA1/2携带者将接受两个低外显率癌症风险等位基因（RAD51放大brca相关风险；APCI1307K表示结肠癌风险）的计算机遗传教育。我们将评估基因检测的吸收水平，并利用自动相互作用检测（AID）探索预测变量之间的关系模式。我们的目的是确定具有不同咨询需求的患者群体，并检查咨询对这些群体的满意度、痛苦和对降低风险的依从性的不同影响。该培训计划通过癌症遗传学、遗传流行病学、分子生物学和高级统计学（潜在类分析、生长曲线分析、层次线性模型和自动相互作用检测）的课程来支持拟议的研究。长期目标是通过提高高危人群对健康保护行为的依从性，促进遗传性癌症综合征的癌症预防和控制工作；然而，这里开发的研究方法可能适用于接受多种筛查建议的平均风险个体（例如，50岁以上接受常规乳腺癌、结直肠癌、宫颈癌和皮肤癌监测的女性）。

DESCRIPTION (provided by applicant): This proposal is for advanced training and mentored research for Dr. Karen Hurley to become an independent behavioral investigator in hereditary cancer risk. It addresses two challenges posed by the genomic revolution: 1) accounting for multiple, interrelated risk-reducing behavior outcomes in the same person, and 2) accounting for individual variation in the relations between predictor variables and behavioral outcomes. Hereditary syndromes often confer risk to several organs at once, yet studies usually assess one screening outcome at a time. Similarly, psychosocial factors are often analyzed as independent predictors; yet within a given person they are interdependent. Developing new assessment and statistical strategies to understand how patients process complex information, and to analyze interrelated behavioral outcomes, will enhance the accuracy and clinical utility of research findings. Study 1 will assess longitudinal patterns of adherence (full, partial or none) to comprehensive, multi-organ screening guidelines in HNPCC patients. Cluster analysis will yield a taxonomy of perceived/risk worry types (e.g., selective worry about one type of cancer vs. pervasive worry) that will be used to predict trajectories of adherence over time. In Study 2, BRCA1/2 carriers will be offered computer-based genetic education for two low penetrance cancer risk alleles (RAD51 amplifies BRCA-related risk; APCI1307K indicates colon cancer risk). We will assess genetic testing uptake levels, and explore patterns of relations between predictor variables using automatic interaction detection (AID). We aim to identify groups of patients with different counseling needs, and to examine the differential impact of counseling on satisfaction, distress, and adherence to risk reduction in these groups. The training plan supports the proposed research with coursework in cancer genetics, genetic epidemiology, molecular biology and advanced statistics (latent class analysis, growth curve analysis, hierarchical linear models, and automatic interaction detection). The long-term goal is promote cancer prevention and control efforts in hereditary cancer syndromes by increasing adherence to health-protective behaviors in high risk individuals; however, the research methods developed here may be applied to average risk individuals who receive multiple recommendations for screening (e.g., women over 50 undergoing routine breast, colorectal, cervical, and skin cancer surveillance).