GSTM1 copy number and promoter haplotype as predictors for risk of recurrence and/or second primary tumor in patients with head and neck cancer

• DOI: 10.2147/pgpm.s35949
• Publication Date: 2013-03-01T15:08:50Z
• Authors: Susan Kadlubar; Zhang; Xifeng Wu; Lin; Yu; Fan; Ning; Huang
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Pharmacogenomics and Personalized Medicine; Therapeutics. Pharmacology; RM1-950; Original Research; 3. Good health

The objective of this study was to determine copy number variant (CNV) and promoter genetic variants in glutathione S-transferase Mu class 1 (GSTM1) the risk recurrence (REC)/second primary tumor (SPT) patients with previously diagnosed early stage head neck cancer. Among 441 subjects, 133 experienced REC and/or an SPT, while 308 had single disease. TaqMan real-time polymerase chain reaction used measure exact GSTM1 direct sequencing region. Multivariate Cox regression analysis performed estimate hazard ratios (HRs) 95% confidence intervals (95% CIs) associated variants. REC/SPT-free survival times were compared by constructing Kaplan-Meier curves differences between tested logrank test. Results showed a significantly decreased REC/SPT (HR = 0.57; CI 0.35-0.95) longer subjects at least two copies homozygous deletion, but not those one GSTM1. -498G, -426G, -339T alleles REC/SPT, HRs 0.11 (0.02-0.85), 0.28 (0.11-0.74) 2.02 (1.07-3.82), respectively. that -339C also increased survival. Further haplotype P(-498G--426G--339C) carriers HR 0.09 0.01-0.71) P(-498C--426A--339T). P(-498C--426A--339T)-containing reporter construct luciferase expression. These results suggest CNV are better predictors REC/SPTs cancer than just measuring presence/absence