GENETIC EPIDEMIOLOGY OF BREAST CANCER--BRCA1 AND BRCA2

乳腺癌的遗传流行病学--BRCA1和BRCA2

• 批准号: 6164238
• 负责人: Susan L. Neuhausen
• 金额: $ 44.23万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6164238
• 关键词: African American; SDS polyacrylamide gel electrophoresis; age at pregnancy; age difference; brca gene; breast neoplasms; cancer risk; caucasian American; clinical research; disease /disorder onset; family genetics; female; gene environment interaction; gene mutation; genetic susceptibility; hormone therapy; human puberty; human subject; longitudinal human study; menopause; neoplasm /cancer epidemiology; neoplasm /cancer genetics; oral contraceptives; ovary neoplasms; parity

DESCRIPTION: (Adapted from the Investigator's Abstract) Many environmental, reproductive, and genetic factors have been associated with an increased risk of breast and ovarian cancers. A family history of breast cancer has been identified as a major risk factor for the development of the disease. A genetic predisposition likely accounts for 5 to 10 percent of breast cancer and ovarian cancer. Approximately 80 percent of inherited early onset breast cancer is attributed to the breast cancer genes, BRCA1 and BRCA2. Among families with the same BRCA1 (BRCA2) mutations, there are differences in age-specific penetrance, lifetime penetrance, proportions of breast and ovarian cancer, and risks of other cancers. This variability suggests there are environmental and genetic factors interacting with the BRCA1 and BRCA2 genes. The identification of predictors of phenotypic expression, not only in terms of type of cancer but also in modulating age at onset, has implications for screening and prevention strategies for women at significantly increased risk of breast and ovarian cancers due to the BRCA1 and BRCA2 genes. This is a proposal to examine the effects of reproductive and genetic factors which may modulate the incidence by age and overall incidence of breast and ovarian cancers in individuals with BRCA1 and BRCA2 mutations. The cohort is composed of Caucasian and African American BRCA1 and BRCA2 mutation carriers. We have already sampled 215 BRCA1 and 141 BRCA2 mutations carriers in our Utah kindreds and will continue to sample within these families to identify all mutation carriers. Little information is available regarding prevalence of BRCA1 and BRCA2 in African Americans, although for women less than 44 years of age, their incidence of breast cancer is higher than for Caucasians. With collaborators in Dallas and Chicago, we propose to contact African American families with a history of breast and/or ovarian cancer, to identify BRCA1 and BRCA2 mutations, and sample within those families to identify all mutations carriers. The cofactors to be examined in this cohort include ages at menarche and menopause, parity, age at first pregnancy, use of oral contraceptives, and hormone replacement therapy. The genetic factors to be investigated include the h-RAS VNTR and carcinogen metabolizing genes GSTT1, GSTM1, CYP2D6, CYP1A1, and EPHX. Survival analysis models will be used to estimate cumulative incidence by age and overall incidence for breast and ovarian cancers stratified by the hormone, reproductive, and genetic factors.

描述：（改编自研究者的摘要）许多环境、 生殖和遗传因素与增加有关 乳腺癌和卵巢癌的风险。 有乳腺癌家族史 已被确定为该疾病发生的主要危险因素。 遗传倾向可能占乳房的 5% 到 10% 癌症和卵巢癌。 大约80%是早期遗传的 乳腺癌的发病归因于乳腺癌基因 BRCA1 和 BRCA2。 在具有相同 BRCA1 (BRCA2) 突变的家族中，有 年龄别外显率、终生外显率、比例的差异 乳腺癌和卵巢癌，以及其他癌症的风险。 这种可变性 表明环境和遗传因素与 BRCA1 和 BRCA2 基因。 表型预测因子的鉴定 表达，不仅在癌症类型方面，而且在调节年龄方面 首先，对妇女的筛查和预防策略产生影响 由于以下原因，患乳腺癌和卵巢癌的风险显着增加 BRCA1 和 BRCA2 基因。 这是一项检查生殖和遗传影响的提案 可能通过年龄和总体发病率调节发病率的因素 具有 BRCA1 和 BRCA2 突变的个体的乳腺癌和卵巢癌。 该队列由白种人和非裔美国人 BRCA1 和 BRCA2 组成 突变携带者。 我们已经采样了 215 个 BRCA1 和 141 个 BRCA2 我们犹他州亲属中的突变携带者，并将继续在 这些家族能够识别出所有突变携带者。 资料很少是 有关非裔美国人中 BRCA1 和 BRCA2 患病率的信息， 尽管对于 44 岁以下的女性来说，她们的乳腺癌发病率 癌症发病率高于白种人。 与达拉斯的合作者 芝加哥，我们建议联系有历史的非裔美国家庭 乳腺癌和/或卵巢癌，以确定 BRCA1 和 BRCA2 突变，以及 在这些家族中进行样本识别所有突变携带者。 这 该队列中要检查的辅助因素包括初潮年龄和 更年期、产次、首次怀孕年龄、口服避孕药的使用，以及 激素替代疗法。 需要研究的遗传因素包括 h-RAS VNTR 和致癌物代谢基因 GSTT1、GSTM1、CYP2D6、 CYP1A1 和 EPHX。 生存分析模型将用于估计 按年龄划分的累积发病率以及乳腺癌和卵巢的总体发病率 癌症按激素、生殖和遗传因素分层。