BRCA1, ORAL CONTRACEPTIVES, AND HORMONAL RISK FACTORS

乳腺癌易感基因BRCA1的突变可能与大量早期诊断的乳腺癌有关。然而，发生乳腺癌的年龄似乎差异很大，即使是来自同一家庭的女性也有相同的突变。 最近的进一步证据表明，BRCA1突变携带者患乳腺癌的风险远低于先前报道的85%。这表明其他遗传或非遗传因素在BRCA1突变女性是否或何时发生乳腺癌中发挥作用。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的使用似乎特别。 对于有家族史的年轻女性来说是有害的。 我们有初步的数据表明BRCA 1突变携带者与OC使用相关的风险比非携带者高得多。 在BRCA1突变携带者中使用OC的这种不利影响可能是由于这些妇女的乳腺细胞增殖增加。 实验证据表明，BRCA 1可能是一种神经诱导的负性生长调节因子。我们建议进行一项以人群为基础的研究，以确定BRCA1突变携带者与OC使用相关的乳腺癌相对风险的比例，以及非携带者与OC使用相关的乳腺癌相对风险。 这些信息随后可用于确定BRCA1突变携带者中与OC使用相关的乳腺癌相对风险。 本研究的次要目的是确定其他激素风险因素（如选定的生殖因素和体育锻炼）是否对BRCA 1突变携带者和非携带者的乳腺癌风险有不同的影响，以确定BRCA 1突变携带者是否具有与携带者不同的乳腺摄影密度特征，并确定乳腺摄影密度是否受OC使用的影响，BRCA1突变携带者与非携带者之间存在差异。这项研究将提供有关BRCA1在乳腺癌病因学中的作用的有价值的流行病学信息，并可能在为BRCA1突变的妇女制定干预方案和适当的咨询方面产生重要结果。

Mutations in the breast cancer susceptibility gene BRCA1 may be involved in a substantial number of breast cancer 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. Further recent evidence suggests that breast cancer risk in BRCA1 mutation carriers is much lower than the previously reported 85%. 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 appears to be particularly. Detrimental in young women with a family history. We have preliminary data suggesting that BRCA1 mutation carriers have a much higher risk associated with OC use than non- carriers. Such a detrimental effect of OC use in BRCA1 mutation carriers could be due to increased breast cell proliferation in these women. Experimental evidence suggests that BRCA1 may be a hormonally induced negative growth regulator. We propose to conduct a population-based study to determine the ration of relative risk of breast cancer associated with OC use in BRCA1 mutation carriers and the relative risk of breast cancer associated with OC use in non-carriers. This information can subsequently be used to determine the relative risk of breast cancer associated with OC use in BRCA1 mutation carriers. The secondary aims of this study are to determine whether other hormonal risk factors such as selected reproductive factors and physical exercise differentially affects breast cancer risk in BRCA1 mutation carriers and non-carriers, to determine whether BRCA1 mutation carriers have different mammographic density profiles that on carriers, and to determine whether mammographic densities are affected by OC use differentially in BRCA1 mutation carriers than non-carriers. 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.