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Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer.
Cancer. 2006 Jun 15; 106(12):2636-44.C

Abstract

BACKGROUND

The objective of this study was to evaluate the effects of polymorphisms in 2 genes in the glutathione S-transferase (GST) family and the mutagen-sensitivity phenotype on the risk of second primary tumors (SPTs) in patients with previously diagnosed early-stage head and neck squamous cell carcinoma. Data were available for 303 patients who were enrolled in a placebo-controlled chemoprevention trial of low-dose 13-cis-retinoic acid to reduce the occurrence of SPTs.

METHODS

A Cox proportional hazards model and survival tree analysis were used to evaluate the association between specified genetic variations and the development of SPTs. The average number of bleomycin-induced chromatid breaks per cell was used to quantify mutagen sensitivity as an individual patient's degree of sensitivity to genotoxicity.

RESULTS

The GST-M1 null genotype was associated with an increased risk for any SPTs (hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.11-3.56) and for tobacco-related SPTs (HR, 2.16; 95% CI, 1.01-4.62) after adjusting for covariates. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with a statistically significant increased risk for SPTs or tobacco-related SPTs after similar adjustment. Simultaneous nonnull status for both GST genotypes was associated with a decreased risk for any SPTs (HR, 0.52; 95% CI, 0.28-0.96) and tobacco-related SPTs (HR, 0.50; 95% CI, 0.22-1.11) compared with null status for GST-M1 accompanied by nonnull status for GST-T1.

CONCLUSIONS

An association was observed between the development of SPTs and the GST-M1 null genotype after successful treatment for early-stage head and neck squamous cell carcinoma. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with an increased risk, and no significant interactions were identified.

Authors+Show Affiliations

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16703596

Citation

Minard, Charles G., et al. "Evaluation of Glutathione S-transferase Polymorphisms and Mutagen Sensitivity as Risk Factors for the Development of Second Primary Tumors in Patients Previously Diagnosed With Early-stage Head and Neck Cancer." Cancer, vol. 106, no. 12, 2006, pp. 2636-44.
Minard CG, Spitz MR, Wu X, et al. Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer. Cancer. 2006;106(12):2636-44.
Minard, C. G., Spitz, M. R., Wu, X., Hong, W. K., & Etzel, C. J. (2006). Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer. Cancer, 106(12), 2636-44.
Minard CG, et al. Evaluation of Glutathione S-transferase Polymorphisms and Mutagen Sensitivity as Risk Factors for the Development of Second Primary Tumors in Patients Previously Diagnosed With Early-stage Head and Neck Cancer. Cancer. 2006 Jun 15;106(12):2636-44. PubMed PMID: 16703596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer. AU - Minard,Charles G, AU - Spitz,Margaret R, AU - Wu,Xifeng, AU - Hong,Waun Ki, AU - Etzel,Carol J, PY - 2006/5/17/pubmed PY - 2006/7/19/medline PY - 2006/5/17/entrez SP - 2636 EP - 44 JF - Cancer JO - Cancer VL - 106 IS - 12 N2 - BACKGROUND: The objective of this study was to evaluate the effects of polymorphisms in 2 genes in the glutathione S-transferase (GST) family and the mutagen-sensitivity phenotype on the risk of second primary tumors (SPTs) in patients with previously diagnosed early-stage head and neck squamous cell carcinoma. Data were available for 303 patients who were enrolled in a placebo-controlled chemoprevention trial of low-dose 13-cis-retinoic acid to reduce the occurrence of SPTs. METHODS: A Cox proportional hazards model and survival tree analysis were used to evaluate the association between specified genetic variations and the development of SPTs. The average number of bleomycin-induced chromatid breaks per cell was used to quantify mutagen sensitivity as an individual patient's degree of sensitivity to genotoxicity. RESULTS: The GST-M1 null genotype was associated with an increased risk for any SPTs (hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.11-3.56) and for tobacco-related SPTs (HR, 2.16; 95% CI, 1.01-4.62) after adjusting for covariates. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with a statistically significant increased risk for SPTs or tobacco-related SPTs after similar adjustment. Simultaneous nonnull status for both GST genotypes was associated with a decreased risk for any SPTs (HR, 0.52; 95% CI, 0.28-0.96) and tobacco-related SPTs (HR, 0.50; 95% CI, 0.22-1.11) compared with null status for GST-M1 accompanied by nonnull status for GST-T1. CONCLUSIONS: An association was observed between the development of SPTs and the GST-M1 null genotype after successful treatment for early-stage head and neck squamous cell carcinoma. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with an increased risk, and no significant interactions were identified. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/16703596/Evaluation_of_glutathione_S_transferase_polymorphisms_and_mutagen_sensitivity_as_risk_factors_for_the_development_of_second_primary_tumors_in_patients_previously_diagnosed_with_early_stage_head_and_neck_cancer_ L2 - https://doi.org/10.1002/cncr.21928 DB - PRIME DP - Unbound Medicine ER -