Precision Assessment and Delivery of Cancer Risks in BRCA 1/2 Mutation Cancers

BRCA 1/2 突变癌症的癌症风险的精确评估和传递

基本信息

批准号：
9567099
负责人：
Jinbo Chen
金额：
$ 64.23万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-18 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9567099
关键词：
Affect Age Age of Onset BRCA1 gene Biological Process Characteristics Clinical Contraceptive Usage Counseling Data Decision Aid Decision Making Disease Exposure to Family history of Fertility Future General Population Generic Drugs Genes Goals Health In Vitro Individual Inherited Intervention Malignant Neoplasms Malignant neoplasm of ovary Menopause Methods Modeling Morbidity - disease rate Mutation Operative Surgical Procedures Oral Contraceptives Pattern Population Prevention approach Prevention strategy Preventive Preventive measure Probability Publishing Recommendation Relative Risks Reporting Reproductive History Risk Risk Assessment Risk Estimate Risk Factors Risk Reduction Salpingo-Oophorectomy Specific qualifier value Subgroup Testing Time Translating Woman Work base cancer prevention cancer risk clinically relevant improved individualized prevention malignant breast neoplasm mortality mutation carrier preference risk minimization translational approach translational impact web-based tool

项目摘要

Project Summary In current risk assessment and counseling practices, all women who test positive for a deleterious BRCA1/2 mutation are quoted the same general range of ovarian cancer risk and are given the same recommendation regarding utilization of risk reducing salpingo- oophorectomy (RRSO) and other preventive measures. We have recently published a model that reports substantial and clinically relevant differences in risk depending on the specific mutation a woman has inherited. In particular, we have recently shown that specific mutations confer an increased risk or earlier age of onset for breast or ovarian cancer compared with the generic risk estimates made for any BRCA1/2 mutation. In addition, risk estimates that consider previous exposure to important risk factors (e.g., reproductive history, oral contraceptive use, or preventive surgery use) may have a large impact on cancer risk estimates in this population. More precise risk information could be critical for optimal decision-making for women who are considering cancer prevention strategies. Based on these initial observations, we propose to develop precision absolute risk models that incorporate information about mutation risk group, to apply in vitro methods to identify new clinically relevant BRCA1/2 mutations and validate their capacity to cause disease, and to gain a better understanding of how personal values affect how individual women interpret and act on risk estimates, for use in a future decision aid intervention. Thus, this proposal will develop a “precision prevention” approach to BRCA1/2-associated cancer risk to lower the chances a woman will die from ovarian cancer, and will have immediate translational impact for women with BRCA1/2 mutations.

项目摘要在当前的风险评估和咨询实践中，所有测试阳性的女性有害的BRCA1/2突变引用了相同的一般癌症风险范围和给出了相同的建议，以降低风险的利用来降低Salpingo- 卵形切除术（RRSO）和其他预防措施。该报告报告了风险的实质性和临床相关差异，具体取决于特定突变女性已经继承了。与乳腺癌或卵巢癌发病年龄的风险增加或更早对任何BRCA1/2突变进行的通用风险估计。以前接触重要的危险因素（例如，复制历史，口服避孕药使用，或或或或或或预防手术的使用）可能会对该人群中的癌症风险估计产生很大影响。更精确的风险信息可能是对最佳决策的批评考虑预防癌症策略。根据最初的观察，我们建议开发精确的绝对风险结合有关突变风险组的信息的模型，将体外方法应用于确定新的临床相关的BRCA1/2突变，并验证其Capace引起疾病，并更好地了解个人价值观如何影响单个女性的解释方式并根据风险估计行动，用于未来的决策援助干预措施。开发了一种用于降低BRCA1/2的癌症风险的“精确预防”方法。可能会有一个女性威利安癌的女性，并会立即进行翻译患有BRCA1/2突变的女性。