Department of Preventive Medicine and Public Health, Creighton University, Omaha.
Ann Oncol. 2013 Nov;24 Suppl 8:viii83-viii95. doi: 10.1093/annonc/mdt313.
An autosomal-dominant inherited trait predisposing women to both breast cancer (BC) and ovarian cancer (OC) was first described in 1971. Subsequent strides were made in identifying mutations in the eventually cloned genes BRCA1 and BRCA2 as being responsible for hereditary BC and OC (HBOC) in many women with early-onset HBOC. More recently, modifiers of BC risk have also been identified and are under study. The biological and molecular genetic pathways for malignant transformation in OC (ovarian epithelium and/or epithelium of the fallopian tube or, possibly, the endometrium and endocervix) remain elusive. The answer to the question 'What have we learned?' which is part of our chapter title unfortunately remains incomplete. However, intensive worldwide research indicates that its malignant transformation is the product of a multi-step process where there is an array of mutations which account for three or more classes of genes, inclusive of proto-oncogenes, tumor suppressor genes and mutator genes. This causal uncertainty heralds an enormous clinical-pathology dilemma, given the fact that epithelial OC, together with related Müllerian duct carcinoma, harbor the highest fatality rates of all gynecologic malignancies.
1971 年首次描述了一种常染色体显性遗传特征，使女性易患乳腺癌（BC）和卵巢癌（OC）。随后，在最终克隆的 BRCA1 和 BRCA2 基因中发现了突变，这些突变被认为是许多早发性 HBOC 女性中遗传性 BC 和 OC（HBOC）的原因。最近，还发现了 BC 风险的修饰因子，并正在进行研究。OC（卵巢上皮和/或输卵管上皮，或者可能是子宫内膜和宫颈）恶性转化的生物学和分子遗传途径仍然难以捉摸。我们章节标题中的问题“我们学到了什么？”的答案不幸仍然不完整。然而，全球范围内的密集研究表明，其恶性转化是一个多步骤过程的产物，其中存在一系列突变，这些突变涉及三个或更多类别的基因，包括原癌基因、肿瘤抑制基因和突变基因。鉴于上皮性 OC 与相关的 Müllerian 导管癌一起是所有妇科恶性肿瘤中死亡率最高的，这种因果不确定性带来了巨大的临床病理困境。
