OVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERS

本次K07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。将进行两个相互联系的研究领域。首先，一系列独立研究、实验室项目和研讨会/会议将提供对遗传流行病学研究中使用的实验室技术、女性癌症的潜在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的研究将确保研究设计、管理和分析技能的发展。本次培训的基础将是一项调查BRCA1/2突变携带者卵巢癌风险和生存率的研究。由于卵巢癌的致死率很高，许多医生建议这些高危妇女采取两种最能有效预防卵巢癌的行为：服用口服避孕药和多生孩子。虽然最近的一项研究确实发现Ocs对BRCA1/2携带者有保护作用，但对该研究设计的担忧质疑其有效性。此外，一份报告表明，对于BRCA1/2突变携带者，使用OC会大大增加患乳腺癌的风险。另一项研究表明，生育更多的孩子会增加（而不是降低）这些女性患卵巢癌的风险。关于brca1 /2相关卵巢癌患者的生存率也有相互矛盾的发现。因此，迫切需要一项精心设计的研究，调查卵巢癌使用和胎次对BRCA1/2携带者卵巢癌风险和生存的影响。我们将使用一项仅限病例的研究来确定携带BRCA1/2突变的女性与不携带这些突变的女性之间Ocs和胎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。我们将从大约400名患有卵巢癌的德系犹太妇女的组织样本中获得BRCA1/2突变状态，这些样本来自宾夕法尼亚州、俄亥俄州、纽约州和佛罗里达州的肿瘤登记处，或参加了美国国立卫生研究所赞助的研究。我们将把这些结果与有关OC使用和奇偶校验的信息联系起来。然后将使用OC和胎次所提供的保护在BRCA1/2突变携带者与非携带者之间进行比较。通过国家死亡指数获取生存状态，比较两组患者的生存差异。这项研究的信息将对临床实践和临床试验的设计产生直接的影响。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.