Nowak Jerzy, Mosor Maria, Ziółkowska Iwona, Wierzbicka Malgorzta, Pernak-Schwarz Monika, Przyborska Marta, Roznowski Krzysztof, Pławski Andrzej, Słomski Ryszard, Januszkiewicz Danuta
Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań Strzeszyńska 32, Poland.
Eur J Cancer. 2008 Mar;44(4):627-30. doi: 10.1016/j.ejca.2008.01.006. Epub 2008 Feb 15.
Homozygous mutation 657del5 within the NBS1 gene is responsible for the majority of Nijmegen breakage syndrome (NBS) cases. NBS patients are characterised by increased susceptibility to malignancies mainly of lymphoid origin. Recently it has been postulated that heterozygous carriers of 657del5 NBS1 mutation are at higher risk of cancer development. The aim of the study was to analyse the frequency of I171V mutation in NBS1 gene in 270 women with breast cancer, 176 patients with larynx cancer, 81 with second primary tumours of head and neck, 131 with colorectal carcinoma and 600 healthy individuals. I171V mutation was present in 17 cancer patients compared with only one in healthy individuals. This constitutes 2.58% in studied patients with malignancies and 0.17% in the control group (P=0.0002; relative risk 1.827; odds ratio 15.886; 95% confidence interval 2.107-119.8). Since DNA was isolated from non malignant cells, all mutations found in cancer patients appeared to be of germinal origin. It can be concluded that NBS1 allele I171V may be a general susceptibility gene in solid tumours.
NBS1基因内的纯合突变657del5是大多数尼曼-匹克氏症候群（NBS）病例的病因。NBS患者的特征是对主要源于淋巴的恶性肿瘤易感性增加。最近有人提出，NBS1基因657del5突变的杂合携带者患癌症的风险更高。本研究的目的是分析270例乳腺癌女性、176例喉癌患者、81例头颈部第二原发性肿瘤患者、131例结直肠癌患者和600名健康个体中NBS1基因I171V突变的频率。17例癌症患者存在I171V突变，而健康个体中只有1例。这在研究的恶性肿瘤患者中占2.58%，在对照组中占0.17%（P = 0.0002；相对风险1.827；优势比15.886；95%置信区间2.107 - 119.8）。由于DNA是从非恶性细胞中分离出来的，癌症患者中发现的所有突变似乎都源于生殖细胞。可以得出结论，NBS1等位基因I171V可能是实体瘤中的一个普遍易感基因。
