Matthias C, Branigan K, Jahnke V, Leder K, Haas J, Heighway J, Jones P W, Strange R C, Fryer A A, Hoban P R
Department of Otorhinolaryngology, Charite-Hospital, Humboldt-University, Berlin, Germany.
Clin Cancer Res. 1998 Oct;4(10):2411-8.
We have examined the correlation of a frequent A/G polymorphism within exon 4 of the cyclin D1 gene (CCND1) with genetic susceptibility and clinical outcome in 384 patients with squamous cell carcinoma (SCC) of the head and neck. CCND1 genotype frequencies were similar in the cases and 191 controls. Furthermore, the CCND1 genotype was not associated with susceptibility to SCC of the larynx, pharynx, or oral cavity. The influence of the CCND1 genotype on clinical outcome was also assessed. We found no correlation between genotype and tumor size (T1-T4), the involvement of nodes at presentation, or patient age and gender. However, the distribution of CCND1 genotypes in cases with poorly differentiated tumors was significantly different to that in patients with well-/moderately differentiated tumors (P = 0.016; chi2(2) = 8.71). Homozygosity for CCND1*G (GG genotype) was associated with poorly differentiated tumors (G3). We used Cox's proportional hazards model to investigate the influence of the CCND1 genotype on disease-free interval. CCND1 GG was associated with reduced disease-free interval [P = 0.001; hazard ratio (HR) = 2.95; 95% confidence interval (CI) = 1.54-5.63]. This remained significant after correction for tumor differentiation (P = 0.013; HR = 2.34; 95% CI = 1.2-4.6) and tumor stage (P = 0.005; HR = 2.64; 95% CI = 1.34-5.19). Analysis of the data from patients with tumors at different sites showed that the CCND1 GG genotype was associated with reduced disease-free interval in laryngeal (P = 0.004; HR = 3.63; 95% CI = 1.44-8.83) and pharyngeal (P = 0.006; HR = 3.48; 95% CI = 1.43-8.46) tumors. This is the first report of an association between CCND1 polymorphism and prognosis in SCC of the head and neck. These data show that the CCND1 GG genotype is an independent prognostic indicator of disease-free interval and supports initial observations in non-small cell lung cancer, that polymorphism within CCND1 influences tumor behavior.
我们检测了细胞周期蛋白D1基因（CCND1）第4外显子常见的A/G多态性与384例头颈部鳞状细胞癌（SCC）患者遗传易感性及临床预后的相关性。CCND1基因型频率在病例组和191例对照组中相似。此外，CCND1基因型与喉、咽或口腔SCC的易感性无关。我们还评估了CCND1基因型对临床预后的影响。我们发现基因型与肿瘤大小（T1 - T4）、初诊时淋巴结受累情况、患者年龄及性别之间无相关性。然而，CCND1基因型在低分化肿瘤患者中的分布与高分化/中分化肿瘤患者显著不同（P = 0.016；卡方值(2)= 8.71）。CCND1*G纯合子（GG基因型）与低分化肿瘤（G3）相关。我们使用Cox比例风险模型研究CCND1基因型对无病生存期的影响。CCND1 GG基因型与无病生存期缩短相关[P = 0.001；风险比（HR）= 2.95；95%置信区间（CI）= 1.54 - 5.63]。在对肿瘤分化程度（P = 0.013；HR = 2.34；95% CI = 1.2 - 4.6）和肿瘤分期（P = 0.005；HR = 2.64；95% CI = 1.34 - 5.19）进行校正后，该相关性仍具有显著性。对不同部位肿瘤患者的数据分析表明，CCND1 GG基因型与喉癌（P = 0.004；HR = 3.63；95% CI = 1.44 - 8.83）和咽癌（P = 0.006；HR = 3.48；95% CI = 1.43 - 8.46）患者的无病生存期缩短相关。这是关于CCND1多态性与头颈部SCC预后相关性的首次报道。这些数据表明，CCND1 GG基因型是无病生存期的独立预后指标，并支持在非小细胞肺癌中的初步观察结果，即CCND1内的多态性影响肿瘤行为。
