Translational Approaches to Melanoma Prevention in Children at High Genetic Risk

 描述（由申请人提供）：概述：这个职业发展奖的目标是为叶莲娜吴博士提供培训和指导的研究经验，这将有助于她过渡到成为一个独立的研究者在高危儿童癌症预防。她的长期目标是成为将遗传风险沟通技术整合到以家庭为中心的行为干预措施中的专家，这些干预措施针对癌症遗传风险高的儿童，以促进癌症预防，早期发现和临床结果预测。研究：黑色素瘤是一种常见的癌症，与显著的发病率和死亡率相关。遗传学和基因检测的进步现在使我们能够识别出患黑色素瘤风险特别高的个体。具体来说，我们现在可以识别携带CDKN 2A/p16基因突变的儿童，这种突变使他们患黑色素瘤的风险增加了70倍，并且易于在更早的年龄发展。虽然遗传风险无法改变，但儿童患黑色素瘤的风险可以通过实施预防行为来减轻，这些行为可以最大限度地减少严重晒伤，这是黑色素瘤的主要风险因素，并建立终身习惯，包括皮肤自我检查以促进早期发现。不幸的是，包括儿童在内的黑色素瘤遗传风险高的个体对预防和筛查行为的依从性不佳，例如定期使用防晒霜或物理屏障以及进行皮肤自我检查。此外，目前还没有转化和综合的行为干预措施，将高危儿童的基因检测结果纳入其中，并针对这些儿童坚持多种黑色素瘤预防行为。这项拟议的研究将导致开发一种以家庭为中心的行为干预措施，以提高黑色素瘤遗传风险高的儿童对黑色素瘤预防行为的依从性。拟议的研究将包括三项研究。研究1（分析来自儿童和青少年黑色素瘤基因检测的第一项前瞻性纵向研究的新获得数据）和研究2（焦点组）将确定影响高危儿童和父母黑色素瘤预防行为的可改变因素，这些因素可能是干预的目标。研究3将涉及以家庭为中心的行为干预的迭代开发和试点测试，该干预包括遗传风险沟通，旨在提高对黑色素瘤预防行为的依从性。将利用研究1和2的结果优化干预措施的内容和形式。主要结果将是干预的可行性和可接受性，以及儿童的预防行为的遵守。将使用自我报告和客观方法，在干预前、干预后和一次随访评估中评估预防行为依从性。紫外线辐射暴露的客观测量将包括紫外线辐射剂量测定法和反射光谱法。这些研究的结果可以为遗传风险信息与癌症高危儿童的预防行为建议的整合提供信息。这项拟议的研究将为吴博士申请R级资金做好准备，以进一步研究基因检测的影响以及与儿童及其父母的风险沟通，并对通过K 07开发的行为干预进行全面测试。这个职业发展奖将使吴博士成为少数几个高危儿童癌症预防行为专家之一，指导这一领域的临床护理。职业发展计划：吴博士是一位儿科心理学家，在儿科坚持医疗方案和对目前患病儿童实施行为干预方面有着坚实的基础。K 07课程，有针对性的培训，研讨会出席和指导的研究经验将提供吴博士需要成为癌症风险沟通和预防遗传风险家庭的独立调查员的技能和经验。在为期5年的培训期间，吴博士将获得癌症遗传学，遗传风险沟通与家庭应用和决策方面的新内容领域知识。她还将获得定性，以患者为中心的方法来设计预防性行为干预的新技能。吴博士与她的导师们一起组建了一支经验丰富、国际认可的导师团队。指导小组成员将在基因检测、遗传风险沟通、黑色素瘤易感性、行为肿瘤学临床试验、定性方法学和癌症预防行为干预措施的开发等补充领域提供指导。亨斯迈癌症研究所，一个国家癌症研究所指定的癌症中心，和犹他州大学提供了一流的环境，为初级教师的职业发展和无与伦比的机会，多学科研究合作在癌症遗传学。独特的现场资源将用于吴博士的K 07培训和研究，包括亨斯迈癌症研究所的遗传咨询共享资源和犹他州大学遗传科学学习中心。

 DESCRIPTION (provided by applicant): Overview: The goal of this career development award is to provide Yelena Wu, PhD, with training and mentored research experiences that will facilitate her transition into being an independent investigator in cancer prevention among high-risk children. Her long-term goal is to become an expert in integrating genetic risk communication techniques into family-focused behavioral interventions targeting children at high hereditary risk for cancer in order to advance cancer prevention, early detection, and prediction of clinical outcomes. Research: Melanoma is a common form of cancer that is associated with significant morbidity and mortality. Advances in genetics and genetic testing now allow us to identify individuals who are at particularly high risk for developing melanoma. Specifically, we can now identify children who carry the CDKN2A/p16 genetic mutation that places them at up to a 70-fold increased risk for melanoma and a predisposition to developing it at an earlier age. While genetic risk cannot be altered, children's risk for melanoma can be mitigated by implementing preventive behaviors that minimize severe sunburns, a primary risk factor for melanoma, and creating lifelong habits that include skin self-examinations to promote early detection. Unfortunately, individuals at high hereditary risk for melanoma, including children, have suboptimal adherence to preventive and screening behaviors, such as regular use of sunscreen or physical barriers and performance of skin self- examinations. Furthermore, there are no translational and comprehensive behavioral interventions that incorporate genetic testing results for at-risk children and target adherence to multiple melanoma preventive behaviors among these children. The proposed research will lead to the development of a family-focused behavioral intervention to improve adherence to melanoma preventive behaviors among children at high hereditary risk for melanoma. The proposed research will include three studies. Study 1 (analysis of newly- available data from the first prospective, longitudinal study of melanoma genetic testing of children and adolescents) and Study 2 (focus groups) will identify modifiable factors that influence melanoma preventive behaviors among high-risk children and parents that can be targets of intervention. Study 3 will involve the iterative development and pilot-testing of a family-focused behavioral intervention that incorporates genetic risk communication and aims to improve adherence to melanoma preventive behaviors. The content and format of the intervention will be optimized using the findings of Studies 1 and 2. The primary outcomes will be the intervention's feasibility and acceptability, as well as children's preventive behavior adherence. Preventive behavior adherence will be assessed pre-intervention, post-intervention, and at one follow-up assessment using both self-report and objective methods. Objective measures of ultraviolet radiation exposure will include ultraviolet radiation dosimetry and reflectance spectroscopy. Findings from these studies could inform the integration of genetic risk information with preventive behavior recommendations to children at high risk for cancer. The proposed research will prepare Dr. Wu to apply for R-level funding to further examine the impact of genetic testing and risk communication with children and their parents and to conduct a fully powered test of the behavioral intervention developed through this K07. This career development award will enable Dr. Wu to become one of the few behavioral experts in cancer prevention among high-risk children to guide this area of clinical care. Career Development Plan: Dr. Wu is a pediatric psychologist with a strong foundation in pediatric adherence to medical regimens and implementation of behavioral interventions for children who are currently ill. The K07 coursework, targeted training, seminar attendance, and mentored research experiences will provide the skills and experiences Dr. Wu needs to become an independent investigator in cancer risk communication and prevention in genetically at-risk families. During the 5-year training period, Dr. Wu will acquire new content area knowledge in cancer genetics, genetic risk communication with application to families, and decision- making. She will also gain new skills in qualitative, patient-centered approaches to designing preventive behavioral interventions. Together with her co-mentors, Dr. Wu has assembled a highly experienced and internationally-recognized mentoring team. The mentoring team members will provide guidance in the complementary areas of genetic testing, genetic risk communication, melanoma predisposition, behavioral oncology clinical trials, qualitative methodology, and development of behavioral interventions for cancer prevention. The Huntsman Cancer Institute, an NCI-designated Cancer Center, and the University of Utah provide superb environments for the career development of junior faculty and unparalleled opportunities for multidisciplinary research collaborations in cancer genetics. Unique, on-site resources that will be used for Dr. Wu's K07 training and research include the Huntsman Cancer Institute's Genetic Counseling Shared Resource and the University of Utah Genetic Science Learning Center.