GENETIC EPIDEMIOLOGY OF BREAST CANCER--BRCA1 AND BRCA2

描述：(改编自《调查者摘要》)许多环境， 生殖和遗传因素与增加的 患乳腺癌和卵巢癌的风险。有乳腺癌家族史的人 已被确定为该病发展的主要风险因素。 遗传倾向可能占乳房的5%到10% 癌症和卵巢癌。约80%的人过早遗传 乳腺癌的发病归因于乳腺癌基因BRCA1和 BRCA2.在具有相同BRCA1(BRCA2)突变的家庭中，有 不同年龄的外显率、终生外显率、 乳腺癌和卵巢癌，以及其他癌症的风险。这种可变性 表明有环境和遗传因素与 BRCA1和BRCA2基因。表型预测因子的识别 表达，不仅在癌症类型方面，而且在调节年龄方面 一开始，对妇女的筛查和预防策略有影响 乳腺癌和卵巢癌的风险显著增加，原因是 BRCA1和BRCA2基因。 这是一项研究生殖和遗传影响的提案。 可按年龄和总体发病率调整发病率的因素 BRCA1和BRCA2突变个体的乳腺癌和卵巢癌。 该队列由高加索人和非裔美国人BRCA1和BRCA2组成 突变携带者。我们已经采集了215个BRCA1和141个BRCA2 我们犹他州家族中的突变携带者，并将继续在 这些家系要识别所有突变携带者。很少的信息是 关于BRCA1和BRCA2在非裔美国人中的流行情况， 虽然对于44岁以下的女性来说，她们的乳房发病率 癌症比高加索人高。与达拉斯的合作者和 芝加哥，我们建议联系有 乳腺癌和/或卵巢癌，以确定BRCA1和BRCA2突变，以及 这些家系内的样本以确定所有突变携带者。这个 在这个队列中要检查的辅助因素包括月经初潮年龄和 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。待调查的遗传因素包括 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 按年龄分列的累计发病率和乳房和卵巢的总发病率 按荷尔蒙、生殖和遗传因素分层的癌症。

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.