Genetic Testing For Men From Hereditary Cancer Families

 描述(申请人提供)：BRCA1和BRCA2突变的遗传咨询和检测现在是有乳腺癌和卵巢癌家族史的妇女的常规临床护理的一部分。携带BRCA突变的女性患乳腺癌和卵巢癌的风险极高。与BRCA突变携带者有血缘关系的男性与他们的女性亲属一样有可能携带突变，并显著增加患乳腺癌的风险。 胰腺癌，特别是前列腺癌。除了患前列腺癌的风险增加外，携带BRCA1/2突变的男性往往比没有突变的男性患上一种更具侵袭性的前列腺癌。尽管风险增加，来自BRCA阳性家庭的男性很少参加遗传咨询和检测。遗传咨询参与率低可能是因为男性低估了检测与个人健康的相关性，缺乏医生推荐，以及与携带家族突变的女性亲属的沟通水平较低。指南建议对BRCA阳性家庭的男性和女性进行遗传咨询转介，咨询和检测参与率较低限制了男性使用BRCA检测结果为其医疗决策提供信息的机会。针对男性BRCA携带者的管理指南建议，从35-40岁开始进行乳腺癌和前列腺癌筛查，非携带者可以通过避免这些测试而受益，而大多数男性不建议进行这些测试。 到目前为止，很少有研究关注BRCA在男性中的咨询和测试。该项目的主要目标是开发和试点一种简短、低成本的干预措施，教育男性关于BRCA遗传咨询和测试的个人相关性，以促进知情决策。我们的次要目标是前瞻性地评估BRCA咨询和测试的结果。我们将对来自已发现BRCA突变的家庭的男性进行形成性研究，以开发基于网络的健康教育干预(WI)。我们将在与常规护理(UC)的随机试验中测试WI。利用我们建立的700多名BRCA突变携带者的登记，我们将从BRCA阳性家族中招募375名男性(自然减员后N=318)，他们有25%-50%的机会携带突变，并将他们随机分配到WI或UC。所有参与者都将获得免费的遗传咨询。我们将在随机化后的2周和6个月进行随访调查。主要结果是：接受遗传咨询和检测以及决策满意度。次要结果是前列腺癌和乳腺癌的筛查和痛苦。这项由渥太华决策支持框架和知情选择模型指导的研究，将通过开发和评估针对突变风险最高的男性的干预措施，具有实际临床意义，可能会改善这一未被研究的群体的癌症控制结果。

 DESCRIPTION (provided by applicant): Genetic counseling and testing for BRCA1 and BRCA2 mutations is now part of routine clinical care for women with a strong family history of breast and ovarian cancer. Women who carry a BRCA mutation are at extremely high risk for breast and ovarian cancer. Men who are related to BRCA mutation carriers are just as likely to harbor a mutation as their female relatives and are significantly increased risk for breast cancer, pancreatic cancer and particularly prostate cancer. In addition to being at increased risk for developing prostate cancer, men who carry a BRCA1/2 mutation tend to develop a much more aggressive form of prostate cancer than men who do not carry a mutation. Despite this elevated risk, men from BRCA positive families rarely participate in genetic counseling and testing. Low participation in genetic counseling is likely due to men's underestimation of the personal health relevance of testing, lack of physician referral and lower levels of communication with their female relatives who carry the familial mutation. Guidelines recommend genetic counseling referral for men and women from BRCA positive families and low counseling and testing participation limits men's opportunities to use BRCA test results to inform their healthcare decisions. Management guidelines for male BRCA carriers recommend breast and prostate cancer screening beginning at age 35-40 and non-carriers can benefit by avoiding these tests, which are not recommended for most men. To date, little research has focused on BRCA counseling and testing among men. The primary goal of this project is to develop and pilot a brief, low cost intervention to educate men about th personal relevance of BRCA genetic counseling and testing in order to facilitate informed decisions. Our secondary goal is to prospectively evaluate the outcomes of BRCA counseling and testing. We will conduct formative research with men from families in which a BRCA mutation has been identified in order to develop a web-based health education intervention (WI). We will test the WI in a randomized trial against usual care (UC). Using our established registry of over 700 BRCA mutation carriers, we will recruit 375 men (N=318 after attrition) from BRCA positive families who have a 25-50% chance of carrying a mutation and randomize them to WI or UC. All participants will be offered free genetic counseling. We will conduct follow-up surveys at 2-weeks and 6-months following randomization. Primary outcomes are: uptake of genetic counseling and testing and decision satisfaction. Secondary outcomes are prostate and breast cancer screening and distress. This investigation, which is guided by the Ottawa Decision Support Framework and the Informed Choice Model, will have practical clinical significance through the development and evaluation of an intervention for men at the highest level of mutation risk, potentially yielding improved cancer control outcomes for this understudied group.