Lynch Henry T, Casey Murray Joseph, Snyder Carrie L, Bewtra Chhanda, Lynch Jane F, Butts Matthew, Godwin Andrew K
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA.
Mol Oncol. 2009 Apr;3(2):97-137. doi: 10.1016/j.molonc.2009.02.004. Epub 2009 Feb 21.
Hereditary ovarian cancer accounts for at least 5% of the estimated 22,000 new cases of this disease during 2009. During this same time, over 15,000 will die from malignancy ascribed to ovarian origin. The bulk of these hereditary cases fits the hereditary breast-ovarian cancer syndrome, while virtually all of the remainder will be consonant with the Lynch syndrome, disorders which are autosomal dominantly inherited. Advances in molecular genetics have led to the identification of BRCA1 and BRCA2 gene mutations which predispose to the hereditary breast-ovarian cancer syndrome, and mutations in mismatch repair genes, the most common of which are MSH2 and MLH1, which predispose to Lynch syndrome. These discoveries enable relatively certain diagnosis, limited only by their variable penetrance, so that identification of mutation carriers through a comprehensive cancer family history might be possible. This paper reviews the subject of hereditary ovarian cancer, with particular attention to its molecular genetic basis, its pathology, and its phenotypic/genotypic heterogeneity.
2009年,估计有22000例卵巢癌新发病例,其中遗传性卵巢癌至少占5%。同年,超过15000人将死于卵巢原发性恶性肿瘤。这些遗传性病例大多符合遗传性乳腺癌-卵巢癌综合征,而几乎所有其余病例都与林奇综合征相符,这两种疾病都是常染色体显性遗传疾病。分子遗传学的进展已导致发现了易患遗传性乳腺癌-卵巢癌综合征的BRCA1和BRCA2基因突变,以及易患林奇综合征的错配修复基因突变,其中最常见的是MSH2和MLH1。这些发现使得相对确切的诊断成为可能,只是受其可变外显率的限制,因此通过全面的癌症家族史来识别突变携带者或许可行。本文综述了遗传性卵巢癌这一主题,尤其关注其分子遗传学基础、病理学以及表型/基因型异质性。
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