Glutathione S-transferase T1 null polymorphism and the risk for head and neck cancer

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Abstract
Inter-regional differences in the distribution of genetic polymorphisms in glutathione S-transferases (GSTs) exist, which may have significant effect on the outcome of other GST polymorphism studies. The GSTT1 null genotype appears to be involved in modulation of the risk for head and neck squamous cell carcinoma (HNSCC). The risk of HNSCC is strongly associated with smoking of cigarettes and consumption of alcohol, resulting in a load of toxins/carcinogens. Detoxification of such exogenous harmful compounds often occurs by phase II enzymes such as GSTs. Proper functioning of these enzymes may be deficient due to the presence of particular genetic polymorphisms in these GSTs, and this may increase the risk for HNSCC. We compared the GSTT1, GSTM1 and GSTP1 genotype frequencies in two groups of healthy blood donors, collected from different but adjacent regions in the Netherlands, with those of a group of patients with HNSCC. The GSTM1,GSTT1 and GSTP1 genotype frequencies in two Dutch Caucasian control populations (n = 207 and n = 285) from different but adjacent geographical regions (Maastricht and Nijmegen; distance, 125 km) and 185 patients with HNSCC from the Maastricht region were determined by PCR-related methods. For the occurrence of the GSTT1 null genotype we found a significant difference (p=0.003) between the two control groups (20.3% vs 33.0% null genotype in the Nijmegen and Maastricht control groups, respectively). Since the HNSCC patients were collected from the Maastricht area, comparison with the Maastricht controls reveals a significant difference for GSTT1 null rates, which are lower in patients vs controls (OR = 0.49, CI = 0.32-0.76).

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