Influence of glutathione s-transferase and cytochrome p450 polymorphisms on prognosis of head and neck cancer

Abstract

The polymorphic gene loci of the detoxifying enzymes GST and CYP are susceptibility factors for head and neck cancer. Recently, they have been associated with outcome in several cancers. Accordingly, we have examined, in patients with squamous cell carcinoma (SCC) of the head and neck, associations between GSTM1, GSTT1, GSTM3, GSTP1, CYP2D6, CYP1A1 and CYP2E1 genotypes and outcome parameters, tumor extension, histological grade, presence of lymph nodes, and recurrence free survival over 5 years. Genotypes were determined by PCR; logistic regression and a step-wise model were used to investigate the influence of the individual genes. GSTT1 0 was associated with T3/T4 tumor lesions in the pharynx and oral cavity (p = 0.029), but not laryngeal SCC cases. GSTT1 0 was also associated with histological differentiation (G3) in the oral cavity /pharynx, but not laryngeal SCC cases, although this association only approached significance (p = 0.069). CYP2D6 PM and HET were associated with lymph node involvement in the laryngeal SCC cases. The data demonstrate site-dependent associations between GSTT1 null and CYP2D6 PM and tumor extension and lymph node involvement in SCC of the head and neck.