Roznowski Krzysztof, Januszkiewicz-Lewandowska Danuta, Mosor Maria, Pernak Monika, Litwiniuk Maria, Nowak Jerzy
Klinika Onkologii, University School of Medical Sciences, Poznan, Poland.
Breast Cancer Res Treat. 2008 Jul;110(2):343-8. doi: 10.1007/s10549-007-9734-1. Epub 2007 Sep 26.
Nijmegen Breakage Syndrome (NBS) is a rare autosomal, recessive disease caused by homozygous mutations in the NBS1 gene. The most common deletion of 5 bp (657del5) in exon 6, which affects mostly the population of Central Europe is observed. Among the typical features of this disorder is that NBS patients experience a high incidence of lymphoid malignancies as well. An increased risk of solid tumors development for 657del5 carriers was the reason to investigate the role of NBS1 gene as a susceptible one for the breast cancer. The purpose of this work is to identify mutations in all 16 exons of the NBS1 gene in the group of the patients with diagnosed breast cancer and the control group of healthy individuals. In the group of 270 women with breast cancer, seven cases of mutated NBS1 gene were revealed. In the subgroup presenting mutated NBS1 gene, the mutation I171V in 5th exon occurred in five cases. It is the first such a discovery concerning breast cancer patients because this mutation had been previously observed only in the course of lymphoid or hematological malignancies. The rate of I171V mutation in the group of breast cancer patients was significantly higher than in the controls (OR: 9.42; 95% CI: 1.09-81.05; P = 0.02). The conclusion is that heterozygous germline mutation I171V in NBS1 gene is a significant risk factor for breast cancer development. It concerns especially the women whose first degree relatives had a previously diagnosed breast cancer (OR: 6.00; 95% CI: 0.98-38.07; P = 0.04). The histopathological and clinical features of breast cancer with I171V mutation suggest accumulation of the negative prognostic factors. The treatment's results however were unexpectedly satisfactory, that is why further investigations are necessary to assess the role of I171V mutation in NBS1 gene as a prognostic and predictive factor for breast cancer.
奈梅亨断裂综合征（NBS）是一种罕见的常染色体隐性疾病，由NBS1基因的纯合突变引起。观察到外显子6中最常见的5个碱基对缺失（657del5），主要影响中欧人群。这种疾病的典型特征之一是NBS患者也有很高的淋巴系统恶性肿瘤发病率。657del5携带者实体瘤发生风险增加，这是研究NBS1基因作为乳腺癌易感基因作用的原因。这项工作的目的是在已确诊乳腺癌的患者组和健康个体对照组中鉴定NBS1基因所有16个外显子中的突变。在270名乳腺癌女性患者组中，发现7例NBS1基因突变。在呈现NBS1基因突变的亚组中，第5外显子的I171V突变出现了5例。这是关于乳腺癌患者的首次此类发现，因为该突变此前仅在淋巴或血液系统恶性肿瘤病程中观察到。乳腺癌患者组中I171V突变率显著高于对照组（比值比：9.42；95%可信区间：1.09 - 81.05；P = 0.02）。结论是NBS1基因中的杂合种系突变I171V是乳腺癌发生的重要危险因素。这尤其涉及一级亲属曾被诊断患有乳腺癌的女性（比值比：6.00；95%可信区间：0.98 - 38.07；P = 0.04）。具有I171V突变的乳腺癌的组织病理学和临床特征提示不良预后因素的积累。然而治疗结果出人意料地令人满意，这就是为什么有必要进一步研究以评估NBS1基因中的I171V突变作为乳腺癌预后和预测因素的作用。
