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Cyclin D1, Glutathione S-Transferase, and Cytochrome P450 Genotypes and Outcome in Patients with Upper Aerodigestive Tract Cancers: Assessment of the Importance of Individual Genes Using Multivariate Analysis¹

Department of Otorhinolaryngology, Virchow-Klinikum, Humboldt-University, Berlin, 10098 Germany [C. M., V. J.]; Department of Mathematics [P. W. J.] and Centre for Cell and Molecular Medicine, School of Postgraduate Medicine [P. R. H., J. E. A., S. F. W., A. A. F., R. C. S.], Keele University, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire, England ST4 7QB

GST, CYP, and CCND1 genotypes have been associated with outcome in several cancers. Accordingly, we have examined, in patients with one squamous cell carcinoma (SCC) of the head and neck, associations between GSTM1, GSTT1, GSTM3, GSTP1, CYP2D6, CYP1A1, CYP2E1, and CCND1 genotypes and the outcome parameters, tumor extension, histological grade, and presence of nodes. We used logistic regression to study, first, each gene individually and, second, in a step-wise model that included all of the genes. Different genes were associated with each outcome parameter. Thus, GSTT1 null was associated with T3/T4 lesions in the oral cavity/pharyngeal (P = 0.029), but not laryngeal, SCC cases. GSTT1 null was also associated with histological differentiation (G3) in the oral cavity/pharyngeal, but not laryngeal, SCC cases, although this association only approached significance (P = 0.069). CCND1 GG was associated with G3 tumors in the oral cavity/pharyngeal (P = 0.011), but not laryngeal, SCC cases. The combination of GSTT1 null/CCND1 GG was also associated with G3 tumors. CYP2D6 PM and HET were associated with lymph node involvement in the laryngeal, but not oral/pharynx, SCC cases. Genes that were individually associated with outcome were also associated with the parameter in the step-wise routine. The GSTT1 null frequency was greater in 39 patients with second primary tumors than in those with one lesion (P = 0.014). The data demonstrate site-dependent associations between GSTT1 null, CCND1 GG, and CYP2D6 PM and tumor extension, differentiation, and nodes.

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