Breast Cancer Risk Modifiers in BRCA Mutation Carriers

描述（申请人提供）：BRCA 1和BRCA 2基因突变携带者的终生乳腺癌风险估计为40- 80%。因此，大约20-60%的携带者活到了老年而没有患上这种疾病，这表明其他基因或个人属性可能会改变携带者的风险。然而，目前，标题是已知的这种个人特征。迫切需要确定哪些（如果有的话）可改变的生活方式特征可能会改变携带者患乳腺癌的风险，以帮助她对预防性乳房切除术等预防性选择做出理性、知情的选择。我们建议使用从年轻（年龄< 50岁）病例（N=425）和对照（N=352）有害BRCA 1或BRCA 2突变携带者中统一收集的数据来评估乳腺癌风险与5个可改变特征之间的关联。这些措施是：口服避孕药使用史、诊断前诊断性或治疗性胸部照射史、饮酒、吸烟以及青春期、青年期和中年期的体力活动模式。我们将重点关注在诊断（病例）或访谈（对照）时年龄在50岁以下的携带者，他们参加了国际乳腺癌研究合作家庭登记（CFRBCS）以及在纽约、安大略和澳大利亚的临床研究。我们将使用非条件logistic回归来估计这些属性与乳腺癌风险相关的比值比，同时控制潜在的混杂因素，并使用稳健的方差估计来解释相关携带者属性中存在的任何相关性。这些来自一大群年轻BRCA 1或BRCA 2突变携带者的可改变特征的数据代表了一种独特的资源，可用于提高我们对绝经前高危女性乳腺癌预防的认识。拟议的分析将提供新的信息替代乳房切除术作为预防战略，这些妇女。

DESCRIPTION (provided by applicant): Lifetime breast cancer risks among carriers of mutations of the genes BRCA1 and BRCA2 have been estimated at 40-80%. Thus some 20-60% of carriers live to advanced ages without developing the disease, which suggests that other genes or personal attributes may modify carriers' risks. At present however, title is known about such personal characteristics. There is urgent need to determine which, if any, modifiable lifestyle characteristics may alter a carrier's risk of developing breast cancer, to assist her in making rational, informed choices about such preventive options as prophylactic mastectomy. We propose to use uniformly collected data from young (aged < 50 years) case (N=425) and control (N=352) carriers of deleterious BRCA1 or BRCA2 mutations to evaluate associations between breast cancer risk and five modifiable characteristics. These are: history of oral contraceptive use, history of diagnostic or therapeutic chest irradiation prior to diagnosis, alcohol consumption, cigarette smoking, and physical activity patterns during puberty, young adulthood and middle age. We will focus on carriers under age 50 years at diagnosis (cases) or interview (controls) who have participated in an international Collaborative Family Registry for Breast Cancer Studies (CFRBCS) and in clinical studies in New York, Ontario and Australia. We will use unconditional logistic regression to estimate odds-ratios relating these attributes to breast cancer risk while controlling for potential confounders, and use robust variance estimators to account for any correlation present in attributes of related carriers. These data on modifiable characteristics from a large group of young carriers of BRCA1 or BRCA2 mutations represent a unique resource for advancing our knowledge about breast cancer prevention in premenopausal women at high risk for the disease. The proposed analysis will provide new information on alternatives to mastectomy as a preventive strategy for these women.