Ziólkowska Iwona, Mosor Maria, Wierzbicka Malgorzata, Rydzanicz Malgorzata, Pernak-Schwarz Monika, Nowak Jerzy
Department of Molecular Pathology, Institute of Human Genetics, Polish Academy of Sciences, Strzeszyñska St 32, Poznan 60-479, Poland.
Cancer Sci. 2007 Nov;98(11):1701-5. doi: 10.1111/j.1349-7006.2007.00594.x.
The high incidence of multiple primary tumors (MPT) is a significant problem in head and neck tumor treatment. Recent studies suggest that carriers of heterozygous mutations in the NBS1 gene have an increased risk of malignant tumor development. The aim of our research was to assess the frequency of NBS1 mutations in patients with larynx cancer only (LC) and with MPT. The MPT group consisted of patients with one cancer localized to the larynx (primary or second) and another at another site. DNA from 175 patients with LC and 93 patients with MPT was analyzed using the single-strand conformation polymorphism method and direct sequencing. We found nine carriers of the I171V mutation among these 268 cancer patients and only one carrier among 500 population controls (0.2%). Four carriers of the I171V mutation were detected among 175 LC patients (2.3%) and five among 93 patients with MPT (5.4%). The frequencies of the I171V mutation carriers in LC and MPT patients were significantly higher than in controls (odds ratio [OR] = 11.7, confidence interval [CI] 1.3-105.2, P = 0.0175 and OR = 28.35, CI 3.27-245.7, P = 0.0005, respectively). In one individual with LC, a novel molecular variant, c.1222 A > G (p.K408E), was identified. No carriers of R215W or 657del5 NBS1 mutations were found in the present study. These findings imply that heterozygous carriers of the I171V mutation are prone to the development of larynx cancer and may, in addition, display an increased risk of second tumors at other sites.
多原发性肿瘤（MPT）的高发病率是头颈肿瘤治疗中的一个重大问题。最近的研究表明，NBS1基因杂合突变携带者发生恶性肿瘤的风险增加。我们研究的目的是评估仅患有喉癌（LC）的患者和患有MPT的患者中NBS1突变的频率。MPT组由一名癌症位于喉部（原发或继发）而另一名癌症位于其他部位的患者组成。使用单链构象多态性方法和直接测序对175例LC患者和93例MPT患者的DNA进行了分析。我们在这268例癌症患者中发现了9名I171V突变携带者，而在500名人群对照中仅发现1名携带者（0.2%）。在175例LC患者中检测到4名I171V突变携带者（2.3%），在93例MPT患者中检测到5名（5.4%）。LC和MPT患者中I171V突变携带者的频率显著高于对照组（优势比[OR]=11.7，置信区间[CI]1.3 - 105.2，P = 0.0175；OR = 28.35，CI 3.27 - 245.7，P = 0.0005）。在一名LC患者中，鉴定出一种新的分子变异，即c.1222 A > G（p.K408E）。在本研究中未发现R215W或657del5 NBS1突变的携带者。这些发现表明，I171V突变的杂合携带者易于发生喉癌，此外，可能还表现出在其他部位发生第二肿瘤的风险增加。
