Eeles R A, Stratton M R, Goldgar D E, Easton D F
CRC Academic Unit of Radiotherapy and Oncology, Royal Marsden Hospital, Sutton, Surrey, U.K.
Eur J Cancer. 1994;30A(9):1383-90. doi: 10.1016/0959-8049(94)90190-2.
A small proportion of breast cancer (perhaps about 5%) and a higher proportion of early onset cases are due to the inheritance of mutations in dominant susceptibility genes which confer a high lifetime risk of the disease. This would equate to about 1250 cases per year in the U.K. and 9000 in the U.S.A. Even within these cases, there is genetic heterogeneity, i.e. there are several genes involved, each giving rise to different patterns of other cancers associated with the familial breast cancer. One such gene (p53) has been identified and a second (BRCA1) has been precisely mapped in the human genome, but further breast cancer predisposition genes remain to be identified. In addition, there are other genes which confer a lower risk of the disease, but may account for a larger proportion of cases, the most important example to date being ataxia telangiectasia. The identification of these genes will enable the entity of familial breast cancer to be more precisely defined and has implications for management of gene carriers with breast cancer and their relatives who are at risk. A major consideration in this new area of cancer genetics is that the identification of gene carriers may become possible on a large scale and this raises ethical and social issues.
一小部分乳腺癌（可能约5%）以及较高比例的早发病例是由于显性易感基因突变的遗传，这些突变会使患该疾病的终生风险很高。这相当于英国每年约有1250例病例，美国每年有9000例。即使在这些病例中，也存在基因异质性，即涉及多个基因，每个基因都会引发与家族性乳腺癌相关的不同其他癌症模式。其中一个这样的基因（p53）已被确定，第二个基因（BRCA1）已在人类基因组中精确定位，但仍有待确定更多的乳腺癌易感基因。此外，还有其他一些基因会使患该病的风险较低，但可能占病例的比例更大，迄今为止最重要的例子是共济失调毛细血管扩张症。这些基因的鉴定将使家族性乳腺癌的实体能够得到更精确的定义，并对患有乳腺癌的基因携带者及其有风险的亲属的管理产生影响。癌症遗传学这一新领域的一个主要考虑因素是，大规模识别基因携带者可能成为现实，这引发了伦理和社会问题。
