Breast Cancer Risk Modifiers in BRCA Mutation Carriers

BRCA 突变携带者的乳腺癌风险调节因素

• 批准号: 6680657
• 负责人: Alice Whittemore
• 金额: $ 33.88万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-20 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6680657
• 关键词: alcoholic beverage consumption; behavioral /social science research tag; body physical activity; brca gene; breast neoplasm /cancer diagnosis; breast neoplasms; cancer risk; clinical research; gene environment interaction; gene mutation; genetic susceptibility; human data; lifestyle; neoplasm /cancer radiation therapy; oral contraceptives; radiation genetics; smoking; statistics /biometry; tobacco abuse; women's health

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.

描述（由申请人提供）：BRCA1 和 BRCA2 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% 的携带者活到高龄却没有患上这种疾病，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，有关此类个人特征的头衔已为人所知。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选择做出合理、明智的选择。我们建议使用从有害 BRCA1 或 BRCA2 突变的年轻（年龄 < 50 岁）病例 (N=425) 和对照 (N=352) 携带者中统一收集的数据来评估乳腺癌风险与五种可改变特征之间的关联。这些是：口服避孕药的使用史、诊断前的诊断或治疗性胸部照射史、饮酒、吸烟以及青春期、青年期和中年期间的体力活动模式。我们将重点关注诊断（病例）或访谈（对照）时年龄在 50 岁以下的携带者，他们参加过国际乳腺癌研究合作家庭登记处 (CFRBCS) 以及纽约、安大略和澳大利亚的临床研究。我们将使用无条件逻辑回归来估计这些属性与乳腺癌风险相关的优势比，同时控制潜在的混杂因素，并使用稳健的方差估计器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 BRCA1 或 BRCA2 突变携带者的可改变特征的数据代表了一种独特的资源，可以提高我们对绝经前高风险女性乳腺癌预防的了解。拟议的分析将提供有关乳房切除术替代方案的新信息，作为这些妇女的预防策略。