文章：

遗传性乳腺癌和卵巢癌风险的修饰因子

Modifiers of risk of hereditary breast and ovarian cancer

原文发布日期：2002-02-01

DOI: 10.1038/nrc726

类型: Review Article

开放获取: 否

要点：

1. Most, but not all, women who carry deleterious mutations in BRCA1 or BRCA2 will develop breast or ovarian cancer. The risk of cancer among mutation carriers varies between families and countries. Several study designs can be used to estimate disease penetrance and modifiers of penetrance.
2. Reasons for variation include different mutations in the same gene (allelic variation) and the effect of modifying genes.
3. Genetic modifiers of breast cancer risk include the androgen receptor, the steroid-hormone receptor coactivator NCOA3 and possibly the DNA-repair gene RAD51.
4. Genetic modifiers of ovarian cancer risk include the HRAS1 oncogene and, possibly, the androgen receptor.
5. Preventive oophorectomy, a non-genetic modifier, reduces the risk of ovarian cancer and of breast cancer in BRCA1-mutation carriers.
6. Non-genetic modifiers of breast cancer risk include tamoxifen and reproductive history (such as parity and breastfeeding).
7. Non-genetic modifiers of ovarian cancer risk include oral contraceptives and (in BRCA1-mutation carriers) tubal ligation.

要点翻译：

1. 大多数（但非全部）携带BRCA1或BRCA2有害突变的女性会发展为乳腺癌或卵巢癌。突变携带者的癌症风险因家族和国家而异。可采用多种研究设计评估疾病外显率及其修饰因素。
2. 风险差异的成因包括同一基因的不同突变（等位基因变异）以及修饰基因的影响。
3. 乳腺癌风险的遗传修饰因子包括雄激素受体、类固醇激素受体共激活因子NCOA3，可能还包括DNA修复基因RAD51。
4. 卵巢癌风险的遗传修饰因子包含HRAS1癌基因，可能还涉及雄激素受体。
5. 预防性卵巢切除术（非遗传修饰因子）可降低BRCA1突变携带者的卵巢癌和乳腺癌风险。
6. 乳腺癌的非遗传修饰因素包括他莫昔芬药物和生育史（如产次和哺乳史）。
7. 卵巢癌的非遗传修饰因素则涵盖口服避孕药及（针对BRCA1突变携带者的）输卵管结扎术。

英文摘要：

Hereditary breast and ovarian cancer is among the most commonly encountered adult genetic disease, and it is increasingly important that geneticists, oncologists, surgeons and gynaecologists are aware of the issues regarding risk assessment, prevention and management of women with inherited susceptibility to cancer. Genetic risk can be modified by external factors, but what are these factors, and how might our knowledge of them help us to better define the risks for individual women and to develop strategies for cancer prevention?

摘要翻译： 

遗传性乳腺癌和卵巢癌是最常见的成人遗传病之一，遗传学家、肿瘤科医生、外科医生和妇科医生必须熟悉风险评估、预防以及管理具有癌症遗传易感性的女性所涉及的问题。遗传风险可受外部因素修饰，但这些因素是什么？我们对其了解又如何有助于更准确地界定个体女性的风险，并制定癌症预防策略？

原文链接：

Modifiers of risk of hereditary breast and ovarian cancer