POLYMORPHISM WITHIN THE CYCLIN D1 GENE IS ASSOCIATED WITH PROGNOSIS IN PATIENTS WITH SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

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 cas es and 191 controls. Furthermore, the CCND1 genotype was not associate d with susceptibility to SCC of the larynx, pharynx, or oral cavity, T he influence of the CCND1 genotype on clinical outcome was also assess ed. We found no correlation between genotype and tumor size (T-1-T-4), the involvement of nodes at presentation, or patient age and gender, However, the distribution of CCND1 genotypes in cases with poorly diff erentiated tumors was significantly different to that in patients with well-/moderately differentiated tumors (P = 0.016; chi(2)(2) = 8.71), Homozygosity for CCND1G (GG genotype) was associated with poorly dif ferentiated tumors (G3), We used Cox's proportional hazards model to i nvestigate the influence of the CCND1 genotype on disease-free interva l. CCND1 GG was associated with reduced disease-free interval [P = 0.0 01; hazard ratio (HR) = 2.95; 95% confidence interval (CI) = 1.54-5.63 ], This remained significant after correction for tumor differentiatio n (P = 0.013; HR = 2.34; 95% CI = 1.24.6) and tumor stage (P = 0.005; HR = 2.64; 95% CI = 1.34-5.19). Analysis of the data from patients wit h tumors at different sites showed that the CCND1 GG genotype was asso ciated 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 bet ween CCND1 polymorphism and prognosis in SCC of the head and neck. The se data show that the CCND1 GG genotype is an independent prognostic i ndicator of disease-free interval and supports initial observations in non-small cell lung cancer, that polymorphism within CCND1 influences tumor behavior.