MULTIPLE RISKS, DECISIONS & BEHAVIORS IN THE GENOMIC ERA

描述(由申请人提供)：该提案旨在为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方面的独立行为调查员。它解决了基因组革命带来的两个挑战：1)解释同一个人的多个相互关联的降低风险的行为结果，2)解释预测变量和行为结果之间的关系中的个体差异。遗传综合征通常会同时给几个器官带来风险，但研究通常一次只评估一个筛查结果。同样，心理社会因素通常被分析为独立的预测因素；然而，在一个特定的人内部，它们是相互依赖的。开发新的评估和统计策略以了解患者如何处理复杂的信息，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患者遵守全面、多器官筛查指南的纵向模式(完全、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)，该分类将用于预测随着时间的推移坚持的轨迹。在研究2中，BRCA1/2携带者将接受两个低外显性癌症风险等位基因的计算机遗传教育(RAD51放大BRCA相关风险；APCI1307K指示结肠癌风险)。我们将评估基因检测的摄取水平，并使用自动交互检测(AID)探索预测变量之间的关系模式。我们的目标是确定具有不同咨询需求的患者组，并检查咨询对这些组的满意度、苦恼和对降低风险的坚持的不同影响。培训计划支持拟议的研究，课程包括癌症遗传学、遗传流行病学、分子生物学和高级统计学(潜伏期分析、生长曲线分析、分层线性模型和自动相互作用检测)。长期目标是通过增加高危个体对健康保护行为的坚持，促进遗传性癌症综合征的癌症预防和控制努力；然而，这里开发的研究方法可能适用于收到多项筛查建议的中等风险个体(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妇女)。

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).