Hereditary breast cancer: Part I. Diagnosing hereditary breast cancer syndromes
Hereditary breast cancer: Part I. Diagnosing hereditary breast cancer syndromes
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DOI：
10.1111/j.1524-4741.2007.00515.x
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发表时间：
2008-01-01
期刊：
影响因子：
2.1
通讯作者：
Lynch, Jane F.
中科院分区：
文献类型：
--
作者：
Lynch, Henry T.;Silva, Edibaldo;Lynch, Jane F.
遗传性乳腺癌 (HBC) 占 BC 总负担的 10% 之多。大多数此类病例将被发现是由于 BRCA 种系突变所致。据估计，另外 15-20% 的 BC 患者将有一名或多名患有 BC 的一级和/或二级亲属。因此，当这些数字合并时，家族性 BC 风险约占 BC 总负担的 20-25%。然而，由于 BC 病因评估中有关家族史的信息通常有限，因此这可能被低估。鉴于 HBC 与多种不同癌症综合征的关联，混杂因素包括其表型和基因型异质性。最常见的情况是与卵巢癌相关，即所谓的遗传性乳腺癌-卵巢癌综合征，由 BRCA1 和 BRCA2 突变引起。更罕见的是，它发生在由 p53 种系突变引起的 Li-Fraumeni 综合征中，其中发现明显早发的 BC 与脑肿瘤、肉瘤、白血病、淋巴瘤、恶性黑色素瘤和肾上腺皮质癌有关。重要的是，与 2002 年确定的发病率相比，2003 年美国女性中年龄调整后的 BC 发病率急剧下降，下降了 6.7%。我们假设，对 BC 遗传学了解的增加可能部分有助于识别高风险患者，从而使这些患者从早期诊断中获益匪浅。
Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC burden. Most of these cases will be found to be due to a BRCA germline mutation. An estimated additional 15-20% of those affected with BC will have one or more first- and/or second-degree relatives with BC. Therefore, when these numbers are combined, familial BC risk accounts for approximately 20-25% of the total BC burden. However, because of the often limited information on family history in the etiologic assessment of BC, this may be an underestimate. Confounding factors include its phenotypic and genotypic heterogeneity, given the association of HBC with a plethora of differing cancer syndromes. Its most common occurrence is its association with ovarian cancer in the so-called hereditary breast-ovarian cancer syndrome due to BRCA1 and BRCA2 mutations. More rarely, it occurs in the Li-Fraumeni syndrome, caused by a p53 germline mutation, in which markedly early-onset BC is found in association with brain tumors, sarcomas, leukemia, lymphoma, malignant melanoma, and adrenal cortical carcinoma. Importantly, the age-adjusted incidence of BC in women in the United States fell sharply, by 6.7%, in 2003, when compared with the rate identified in 2002. We postulate that increasing knowledge about the genetics of BC may have partially contributed to the identification of high-risk patients who thereby may have benefited significantly from early diagnosis.