Cyclin D1, glutathione S-transferase, and cytochrome P450 genotypes and outcome in patients with upper aerodigestive tract cancers: Assessment of theimportance of individual genes using multivariate analysis

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, GS TM3, GSTP1, CYP2D6, CYP1A1, CYP2E1, and CCND1 genotypes and the outcome par ameters, tumor extension, histological grade, and presence of nodes. We use d logistic regression to study, first, each gene individually and, second, in a step-wise model that included all of the genes. Different genes were a ssociated 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 differentiati on (G3) in the oral cavity/pharyngeal, but not laryngeal, SCC cases, althou gh this association only approached significance (P = 0.069). CCND1 GG was associated with G3 tumors in the oral cavity/pharyngeal (P = 0.011), but no t laryngeal, SCC cases. The combination of GSTT1 null/CCND1 GG was also ass ociated with G3 tumors. CYP2D6 PM and HET were associated with lymph node i nvolvement in the laryngeal, but not oral/pharynx, SCC cases. Genes that we re individually associated with outcome were also associated with the param eter in the step-wise routine. The GSTT1 null frequency was greater in 39 p atients with second primary tumors than in those with one lesion (P = 0.014 ). The data demonstrate site-dependent associations between GSTT1 null, CCN D1 GG, and CYP2D6 PIM and tumor extension, differentiation, and nodes.