Improving the Estimation and Communication of Ovarian Cancer Risk Among BRCA1/2 C

改善 BRCA1/2 C 人群卵巢癌风险的评估和沟通

基本信息

批准号：
8380816
负责人：
MARY Beryl DALY
金额：
$ 34.36万
依托单位：
FOX CHASE CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8380816
关键词：
Age Age of Onset BRCA1 gene BRCA2 gene Breast Communication Complement DNA Damage Decision Aid Decision Making Development Diagnosis Epidemiology Evaluation Family General Population Genes Genetic Genetic Counseling Genotype Germ-Line Mutation Goals Hereditary Breast and Ovarian Cancer Syndrome Incidence Individual Inherited Instruction Malignant Neoplasms Malignant neoplasm of ovary Menopause Modality Modeling Morbidity - disease rate Mutation Nature Online Systems Operative Surgical Procedures Oral Contraceptives Ovariectomy Pathway interactions Patients Pattern Penetrance Population Prevalence Prevention strategy Process Relative (related person)Risk Risk Estimate Risk Factors Risk Management Risk Reduction Role Salpingo-Oophorectomy Screening procedure Site Testing Time Translating Uncertainty Woman base cancer prevention cancer risk cancer site child bearing cost improved malignant breast neoplasm mutation carrier non-genetic ovarian cancer prevention prophylactic repaired reproductive

项目摘要

Germline mutations in the BRCA1/2 genes are associated with significant risk of developing ovarian cancer. However, there is substantial interindividual variability in both the incidence rates and age at diagnosis in BRCA1/2 mutation carriers, implying that while germline mutations in BRCA1/2 may be necessary to explain the Mendelian pattern of cancer in some families, they may not be sufficient to completely describe interindividual variability in cancer risk. Although there is a wealth of epidemiologic information about exposure-related risk modifiers of ovarian cancer in the general population, their role in hereditary ovarian cancer is not well defined. Our current model of hereditary ovarian cancer risk prediction is based on prevalence estimates derived from small, selective populations, which compromises our ability to personalize ovarian cancer prevention strategies. Currently risk reducing salpingo-oophorectomy (RRSO) offers the highest degree of risk reduction (70-95%). Because of the younger age of onset of ovarian cancer in women with BRCA1/2 mutations, RRSO is recommended at age 35 or when childbearing is complete, often inducing surgical menopause and its associated short- and long-term morbidities. Without more specific estimates of the individual risk of developing ovarian cancer or the age of onset, women considering RRSO must weigh the pros and cons of undergoing surgery and consider the optimal timing of RRSO in the face of uncertainty, leading to significant numbers of women who choose not to undergo RRSO, or who delay the decision until they reach menopause. Evidence suggests that additional modifying factors influence cancer penetrance among BRCA1/2 mutation carriers. A better understanding of the pathways that modify both ovarian cancer incidence and its timing could lessen the uncertainty associated with ovarian cancer risk estimates and translate into more specific cancer prevention strategies for individual women, based on their personal modifier profile. We propose an enhancement of the current prevalence model through: 1) identification and quantification of reproductive and exposure-related risk factors involved in DNA damage recognition and repair pathways that influence 8RCA ¿//2-associated ovarian cancer risk; 2) exploration of their interaction with genotypes at other loci; and 3) development and evaluation of a web-based patient decision aid (PtDA) to complement the genetic counseling session and facilitate decision-making regarding hereditary ovarian cancer risk management. RELEVANCE (See instructions): Prophylactic oophorectomy offers the greatest degree of protection from ovarian cancer in women with mutations in BRCA1/2. However, the decision to undergo surgery is challenged by the uncertainties of individual risk and the adverse short- and long-term consequences of the surgery. The goal of this project is to investigate genetic and non-genetic factors which might provide more precise estimates of risk, and incorporate this personalized risk information into a decision aid to complement the testing process.

BRCA1/2基因中的种系突变与发生卵巢的重大风险有关癌症。 BRCA1/2突变载体中的诊断，这意味着虽然BRCA1/2中的种系突变可能为要解释躯体中癌症的孟德尔癌模式所必需的，它们可能不是附加图完全描述癌症风险的个体变异性。有关普通人群中与暴露有关风险改性剂卵巢癌的信息，它们在遗传性卵巢癌不是为了定义。是基于源自小的，选择性普及的流行率估计值，这会损害我们的能力个性化卵巢癌预防策略。（RRSO）提供最高的风险风险操作（70-95％）。 BRCA1/2突变女性的卵巢癌在35岁时推荐RRSO或生育是完整的，通常会引起手术更年期ATS与短期相关病毒性。优胜者，同意RSO的妇女必须加重接受手术的专业人士和统一面对不确定性，RRSO的最佳时机，导致大量选择的女性不要经历RRSO，或者谁将决定延迟到更年期。其他修饰因素会影响BRCA1/2突变携带者之间的癌症了解修改卵巢取消和时机的途径可能会使您与卵巢癌风险估计相关的不确定性并转化为更具体的癌症我们根据其个人修饰符的个人资料提出了ANN的预防策略通过以下方式增强当前患病率模型：1）鉴定和定量生殖 DNA损伤识别途径涉及的与暴露有关的风险因素 8RCA¿ // 2-相关的卵巢癌风险； 2）探索其与其他基因座的相互作用； 3）开发和评估基于网络的患者决策援助（PTDA）以编译遗传咨询会议并促进有关风险管理的决策。相关性（请参阅教学）：预防性卵巢切除术在有患有卵巢癌的卵巢癌中提供了最大程度的保护。 BRCA1/2中的突变。个人风险和手术的短期和长期后果。是研究遗传和非遗传因素，这些因素可能会提供更精确的风险和风险估计。将此个性化风险信息纳入用于补充测试过程的Adecision援助中。