Górski Bohdan, Debniak Tadeusz, Masojć Bartlomiej, Mierzejewski Marek, Medrek Krzysztof, Cybulski Cezary, Jakubowska Anna, Kurzawski Grzegorz, Chosia Maria, Scott Rodney, Lubiński Jan
Department of Genetics and Pathology, Pomeranian Academy of Medicine, Szczecin 70-111, Al. Powst. Wlkp. 72, Poland.
Int J Cancer. 2003 Sep 1;106(3):379-81. doi: 10.1002/ijc.11231.
In this report the proportion of consecutive and familial breast cancer cases harboring the 657del5 of exon 6 of the NBS1 gene was determined to assess whether it is associated with the increased risk of breast cancer development. The study consisted of 3 groups of patients: a series of consecutive 150 patients with histologically confirmed breast cancer, diagnosed under the age of 50 in the city of Szczecin; a series of 80 breast cancer patients with a family history of breast cancer in their first-degree relatives; and a series of 530 consecutive individuals without the diagnosis of breast cancer selected at random by family doctors from the city of Szczecin. Molecular examination included allele-specific PCR assay for the common Slavic NBS1 mutation (657del5), LOH analysis using denucleotide CA repeat microsatellite markers, haplotype analysis and sequencing. The NBS1 founder mutation was detected in 2 of 150 (1.3%) consecutive breast cancer cases diagnosed under the age of 50 years; in 3 of 80 familial breast cancer cases (3.7%); and in 3 of 530 individuals (0.6%) from the general population. Examination of tumor DNA from patients with the NBS1 mutation (groups A and B) revealed loss of heterozygosity (LOH) in all cases. Additional haplotype analysis revealed that allelic loss affects specifically wild-type alleles. The majority of probands with breast cancer and the NBS1 mutation had a positive family history of breast cancer in their first-degree relatives. It appears that the 657del5 mutation in exon 6 of the NBS1 gene is responsible for the occurrence of a small but significant proportion of familial breast cancer patients.
在本报告中，确定了携带NBS1基因第6外显子657del5突变的连续性和家族性乳腺癌病例的比例，以评估其是否与乳腺癌发生风险增加相关。该研究包括3组患者：一组是在什切青市确诊的150例组织学确诊的乳腺癌患者，年龄在50岁以下；一组是80例一级亲属中有乳腺癌家族史的乳腺癌患者；还有一组是什切青市的家庭医生随机挑选的530例未诊断出乳腺癌的连续个体。分子检测包括针对常见的斯拉夫NBS1突变（657del5）的等位基因特异性PCR检测、使用二核苷酸CA重复微卫星标记的杂合性缺失（LOH）分析、单倍型分析和测序。在150例50岁以下确诊的连续性乳腺癌病例中有2例（1.3%）检测到NBS1奠基者突变；在80例家族性乳腺癌病例中有3例（3.7%）；在普通人群的530例个体中有3例（0.6%）。对NBS1突变患者（A组和B组）的肿瘤DNA检测显示，所有病例均有杂合性缺失（LOH）。进一步的单倍型分析表明，等位基因缺失特异性地影响野生型等位基因。大多数患有乳腺癌且携带NBS1突变的先证者一级亲属中有乳腺癌家族史。看来NBS1基因第6外显子的657del5突变导致了一小部分但比例显著的家族性乳腺癌患者的发病。
