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谷胱甘肽S-转移酶T1基因缺失多态性与头颈癌风险

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

作者信息

Oude Ophuis Michel B, Manni Johannes J, Peters Wilber H M

机构信息

Dept. of Otorhinolaryngology, Head and Neck Surgery, University Hospital Maastricht, The Netherlands.

出版信息

Acta Otolaryngol. 2006 Mar;126(3):311-7. doi: 10.1080/00016480500416355.

Abstract

CONCLUSIONS

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).

BACKGROUND

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.

SUBJECTS AND METHODS

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.

RESULTS

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).

摘要

结论

谷胱甘肽S-转移酶(GSTs)基因多态性分布存在区域间差异,这可能对其他GST多态性研究结果产生重大影响。GSTT1无效基因型似乎参与了头颈部鳞状细胞癌(HNSCC)风险的调节。

背景

HNSCC的风险与吸烟和饮酒密切相关,会导致大量毒素/致癌物。此类外源性有害化合物的解毒通常由II期酶如GSTs完成。由于这些GSTs中存在特定的基因多态性,这些酶的正常功能可能会不足,这可能会增加HNSCC的风险。我们比较了从荷兰不同但相邻地区收集的两组健康献血者与一组HNSCC患者的GSTT1、GSTM1和GSTP1基因型频率。

对象与方法

采用PCR相关方法测定了来自不同但相邻地理区域(马斯特里赫特和奈梅亨;距离125公里)的两组荷兰白种人对照组(n = 207和n = 285)以及来自马斯特里赫特地区的185例HNSCC患者的GSTM1、GSTT1和GSTP1基因型频率。

结果

对于GSTT1无效基因型的出现,我们发现两个对照组之间存在显著差异(p = 0.003)(奈梅亨和马斯特里赫特对照组的无效基因型分别为20.3%和33.0%)。由于HNSCC患者是从马斯特里赫特地区收集的,与马斯特里赫特对照组相比,GSTT1无效率存在显著差异,患者的无效率低于对照组(OR = 0.49,CI = 0.32 - 0.76)。

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