ORAL CONTRACEPTIVES, HORMONAL RISK FACTORS AND BRCA1

描述：（申请人描述）项目C：口服避孕药， 激素风险因素和BRCA 1。乳腺癌中的突变 易感基因BRCA 1可能与相当数量的乳腺癌相关， 早期诊断的癌症。然而，患乳腺癌的年龄 发生的情况似乎有很大的不同，即使是在同一个家庭的妇女， 相同的突变。这表明其他遗传或非遗传因素 在BRCA 1女性是否或何时发生乳腺癌中发挥作用 突变 流行病学证据表明，口服避孕药（OC）的使用在早期 年龄可能会增加患乳腺癌的风险。此外，OC的使用可能特别 对有家族史的女性有害。一些环境风险 外源性激素使用以外的因素也可能通过激素发挥作用。 机制;这些包括第一次生育的年龄，产次，可能的堕胎， 体育锻炼。所有这些因素都可以被操纵，因此， 对预防的影响。这些“荷尔蒙”风险因素似乎 不同的，如果不是相反的，影响妇女与家族史比， 没有这样的历史。原因不明。BRCA1 在实验研究中，表达似乎受激素调节。 此外，有家族史的女性更容易发生BRCA 1突变。 因此，有可能通过家庭的表观效应修改 历史是由BRCA 1状态引起的。 我们建议进行一项基于人群的研究，调查是否 特定BRCA 1突变的存在改变1）口服 避孕药具的使用，2）“荷尔蒙”风险因素的影响，如年龄 第一次生育，怀孕次数和堕胎次数，以及3） 体育锻炼对乳腺癌风险的保护作用。此外，本发明还提供了一种方法， 这项研究将提供关于这些突变频率的信息， 年轻乳腺癌患者，我们将探讨 BRCA 1状态和其他乳腺癌风险因素，如乳房X线检查 密度 这项研究将提供有价值的流行病学信息的作用 BRCA 1在乳腺癌病因学中的作用，并可能在以下方面产生重要结果： 制定干预方案和适当的咨询妇女与 BRCA 1突变。

Description: (Applicant's Description) Project C: Oral Contraceptives, Hormonal Risk Factors, and BRCA1. Mutations in the breast cancer susceptibility gene BRCA1 may be involved in a substantial number of breast cancers diagnosed at an early age. However, the age at which breast cancer occurs appears to vary substantially, even in women from the same family with the same mutation. This suggests that other, genetic or non-genetic, factors play a role in whether or when breast cancer occurs in women with a BRCA1 mutation. Epidemiological evidence suggests that oral contraceptive (OC) use at an early age may increase risk of breast cancer. Further, OC use may be particularly detrimental in women with a family history. A number of environmental risk factors other than exogenous hormone use probably also work through a hormonal mechanism; these include age at first birth, parity, possibly abortion, and physical exercise. All these factors can be manipulated, and therefore have implications for prevention. These "hormonal" risk factors appear to have different, if not opposite, effects in women with a family history than in women with no such history. The reason for this is unknown. However, BRCA1 expression appears to be regulated by hormones in experimental studies. Further, women with a family history are more likely to have a BRCA1 mutation. It is therefore possible that the apparent effect modification by family history is caused by BRCA1 status. We propose to conduct a population-based study that investigates whether the presence of specific BRCA1 mutations modify 1) the effects of oral contraceptive use, 2) the effects of "hormonal" risk factors such as age at first birth, number of pregnancies, and number of abortions, and 3) the protective effect of physical exercise, on breast cancer risk. In addition, this study will provide information as to the frequency of these mutations in younger breast cancer patients, and we will explore the associations between BRCA1 status and other breast cancer risk factors such as mammographic densities. This study will provide valuable epidemiologic information regarding the role of BRCA1 in breast cancer etiology, and could yield important results in developing intervention regimens and appropriate counseling for women with a BRCA1 mutation.