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 cases and 191 controls....

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Bibliographic Details
Published in:Clinical cancer research 1998-10, Vol.4 (10), p.2411-2418
Main Authors: MATTHIAS, C, BRANIGAN, K, JAHNKE, V, LEDER, K, HAAS, J, HEIGHWAY, J, JONES, P. W, STRANGE, R. C, FRYER, A. A, HOBAN, P. R
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - mortality
Carcinoma, Squamous Cell - pathology
Cyclin D1 - genetics
Female
Genotype
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - mortality
Head and Neck Neoplasms - pathology
Humans
Male
Medical sciences
Middle Aged
Neoplasm Recurrence, Local
Otorhinolaryngology (head neck, general aspects and miscellaneous)
Otorhinolaryngology. Stomatology
Polymorphism, Genetic
Prognosis
Tumors
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Summary: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.
ISSN:1078-0432
1557-3265