Abstract 885: GSTM1 CNV and promoter SNPs are associated with REC/SPT and survival after Retinoid Acid treatment for head and neck cancer

Abstract

Abstract Purpose: This study sought to determine if copy number variant (CNV) combined with other genetic variants in the glutatione S-transferase Mu class1 (GSTM1) promoter have an important impact on recurrence and overall survival in head and neck cancer patients after retinoid acid treatment. Experimental Method: This study included 441 head and neck patients treated with retinoid acid. Among these cases, 133 experienced recurrence of disease and/or a second primary tumor, while 308 have single primary disease. TaqMan real-time PCR and direct sequencing were used to determine genetic variants in GSTM1. Recurrence and secondary primary tumor (REC/SPT) were evaluated by logistic regression modeling and overall survival was estimated by Kaplan-Meier analysis using STATA. Results: Regression analysis revealed significantly decreased REC/SPT and increased overall survival in subjects with at least 2 copies of GSTM1 (OR=0.57; 95%CI=0.35-0.95) but not in those with 1 copy of the gene. Kaplan-Meier survival analysis also revealed longer overall survival in patients with at least 2 copies of GSTM1. Allele frequency analysis showed −498 C>G, −426 A>G, −339 C>T polymorphisms were significantly associated with REC/SPT in head and neck cancer patients a(OR 0.12 (0.02-0.87), 0.30 (0.11-0.80) and 1.87 (1.00-3.51), respectively. Further survival analysis demonstrated that the −498G, −426G and −339C alleles significantly increased the overall survival in head and neck cancer subjects. Conclusion: These results suggest the GSTM1 CNV combined with single nucleotide polymorphisms is a better predictor of REC/SPT and overall survival of head and neck cancer after retinoic acid treatment than just measuring the presence/absence of GSTM1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 885.