Bergthorsson J T, Ejlertsen B, Olsen J H, Borg A, Nielsen K V, Barkardottir R B, Klausen S, Mouridsen H T, Winther K, Fenger K, Niebuhr A, Harboe T L, Niebuhr E
Department of Medical Genetics, Institute for Medical Biochemistry and Genetics, Panum Institute, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
J Med Genet. 2001 Jun;38(6):361-8. doi: 10.1136/jmg.38.6.361.
A small fraction of breast cancer is the result of germline mutations in the BRCA1 and BRCA2 cancer susceptibility genes. Mutation carriers frequently have a positive family history of breast and ovarian cancer, are often diagnosed at a young age, and may have a higher incidence of double or multiple primary breast tumours than breast cancer patients in general.
To estimate the prevalence and spectrum of BRCA1 and BRCA2 mutations in young Danish patients affected with bilateral or multifocal breast cancer and to determine the relationship of mutation status to family history of cancer.
From the files of the Danish Breast Cancer Cooperative Group (DBCG), we selected 119 breast cancer patients diagnosed before the age of 46 years with either bilateral (n=59) or multifocal (n=61) disease.
DNA from the subjects was screened for BRCA1 and BRCA2 mutations using single strand conformation analysis (SSCA) and the protein truncation test (PTT). Observed and expected cancer incidence in first degree relatives of the patients was estimated using data from the Danish Cancer Registry.
Twenty four mutation carriers were identified (20%), of whom 13 had a BRCA1 mutation and 11 carried a BRCA2 mutation. Two mutations in BRCA1 were found repeatedly in the material and accounted for seven of the 24 (29%) mutation carriers. The mutation frequency was about equal in patients with bilateral (22%) and multifocal breast cancer (18%). The incidence of breast and ovarian cancer was greatly increased in first degree relatives of BRCA1 and BRCA2 mutation carriers, but to a much lesser degree in relatives of non-carriers. An increased risk of cancer was also noted in brothers of non-carriers.
A relatively broad spectrum of germline mutations was observed in BRCA1 and BRCA2 and most of the mutations are present in other populations. Our results indicate that a diagnosis of bilateral and multifocal breast cancer is predictive of BRCA1 and BRCA2 mutation status, particularly when combined with information on the patients' age at diagnosis and family history of breast/ovarian cancer.
一小部分乳腺癌是由乳腺癌易感基因BRCA1和BRCA2的种系突变引起的。突变携带者通常有乳腺癌和卵巢癌的阳性家族史，常被诊断为年轻患者，并且与一般乳腺癌患者相比，可能有更高的双侧或多发原发性乳腺肿瘤发生率。
估计丹麦年轻双侧或多灶性乳腺癌患者中BRCA1和BRCA2突变的患病率和谱，并确定突变状态与癌症家族史的关系。
从丹麦乳腺癌合作组（DBCG）的档案中，我们选择了119例46岁之前诊断为双侧（n = 59）或多灶性（n = 61）疾病的乳腺癌患者。
使用单链构象分析（SSCA）和蛋白质截短试验（PTT）对受试者的DNA进行BRCA1和BRCA2突变筛查。使用丹麦癌症登记处的数据估计患者一级亲属中观察到的和预期的癌症发病率。
鉴定出24名突变携带者（20%），其中13名有BRCA1突变，11名携带BRCA2突变。在材料中反复发现BRCA1的两个突变，占24名（29%）突变携带者中的7名。双侧（22%）和多灶性乳腺癌患者的突变频率大致相等。BRCA1和BRCA2突变携带者的一级亲属中乳腺癌和卵巢癌的发病率大大增加，但在非携带者的亲属中程度要小得多。在非携带者的兄弟中也注意到癌症风险增加。
在BRCA1和BRCA2中观察到相对广泛的种系突变谱，并且大多数突变存在于其他人群中。我们的结果表明，双侧和多灶性乳腺癌的诊断可预测BRCA1和BRCA2突变状态，特别是与患者诊断时的年龄和乳腺癌/卵巢癌家族史信息相结合时。
