OVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERS

这个K 07职业奖培训的目标是获得分子和遗传癌症流行病学研究所需学科的专业知识，重点是女性癌症。将进行两个相互关联的研究领域。 首先，一系列的独立研究，实验室项目和研讨会/会议将提供遗传流行病学研究中采用的实验室技术，女性癌症的基础生物学，以及遗传流行病学研究的临床相关性的理解。 其次，流行病学和生物统计学研究将确保研究设计、管理和分析技能的发展。 这项培训的基石将是一项研究，调查BRCA 1/2突变携带者的卵巢癌风险和生存率。 由于卵巢癌的病死率非常高，许多医生建议这些高危女性从事两种最能有效预防卵巢癌的行为：使用口服避孕药（OCs）和多生孩子。 虽然最近的一项研究确实发现OCs对BRCA 1/2携带者有保护作用，但对研究设计的担忧质疑其有效性。 此外，一份报告表明，对于BRCA 1/2突变携带者，OC的使用大大增加了乳腺癌的风险。 另一项研究表明，生更多的孩子会增加（而不是减少）这些女性患卵巢癌的风险。 关于BRCA 1/2相关卵巢癌患者的生存率也有相互矛盾的发现。因此，迫切需要一项设计良好的研究，调查OC使用和产次对BRCA 1/2携带者卵巢癌风险和生存率的影响。 我们将使用仅病例研究来确定携带BRCA 1/2突变的女性与不携带这些突变的女性之间的OCs和产次对卵巢癌的保护作用，我们将确定两组之间是否存在生存差异。 我们将从宾夕法尼亚州、俄亥俄州、纽约和佛罗里达的肿瘤登记处确定的约400名患有卵巢癌的德系犹太妇女或参加NIH赞助的研究的妇女的库存组织标本中获得BRCA 1/2突变状态。 我们将把这些结果与OC使用和奇偶校验的信息联系起来。 然后将比较BRCA 1/2突变携带者与非携带者之间OC使用和产次提供的保护。 将从国家死亡指数中获得生存状态，并比较两组之间的生存差异。本研究的信息将对临床实践和临床试验的设计产生直接影响。此外，该培训将提供成为女性癌症分子和遗传流行病学独立研究人员所需的技能和经验。

The goal of this K07 Career Award training is to acquire expertise in the requisite disciplines for molecular and genetic cancer epidemiology research, with an emphasis on femal cancers. Two interlocking areas of study will be pursued. First, a series of independent studies, laboratory projects and seminars/conferences will provide an understanding of the laboratory techniques employed in genetic epidemiology studies, the underlying biology of female cancers, and the clinical relevance of genetic epidemiology research. Second, studies in epidemiology and biostatistics will ensure the development of study design, management and analysis skills. The cornerstone of this training will be a study investigating ovarian cancer risks and survival among BRCA1/2 mutation carriers. Because the case fatality rate of ovarian cancer is so high, many doctors advise these high-risk women to engage in the two behaviors that most strongly prevent ovarian cancer: using oral contraceptives (Ocs) and bearing more children. While one recent study did find Ocs to be protective for BRCA1/2 carriers, concerns about the study's design question its validity. Moreover, one report suggests that for BRCA1/2 mutation carriers, OC use substantially increases breast cancer risk. Another study suggests that having more children increases (rather than decreases) ovarian cancer risk in these women. There are also contradictory findings on the survival of BRCA1/2-associated ovarian cancer patients. Therefore, a well-designed study investigating the effect of OC use and parity on ovarian cancer risk and survival in BRCA1/2 carriers is urgently needed. We will use a case-only study to determine the protectiveness of Ocs and parity against ovarian cancer among women carrying BRCA1/2 mutations versus among women not carrying these mutations, and we will determine whether there is a survival difference between the two groups. We will obtain BRCA1/2 mutation status from banked tissue specimens of about 400 Ashkenazi Jewish women with ovarian cancer identified from tumor registries in Pennsylvania, Ohio, New York and Florida or who participated in an NIH-sponsored study. We will link these results to information on OC use and parity. The protection afforded by OC use and parity will then be compared among BRCA1/2 mutation carriers versus among non-carriers. Survival status will be obtained from the National Death Index and the differences in survival between the two groups will be compared. The information from this study will have immediate implications for clinical practice and for the design of clinical trials. Additionally, this training will provide the skills and experience needed to become an independent researcher in the molecular and genetic epidemiology of female cancers.