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谷胱甘肽S-转移酶M1和细胞色素P450 1A1基因多态性与头颈癌发生的相关性

Relevance of glutathione S-transferase M1 and cytochrome P450 1A1 genetic polymorphisms to the development of head and neck cancers.

作者信息

Reszka Edyta, Czekaj Piotr, Adamska Jolanta, Wasowicz Wojciech

机构信息

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.

出版信息

Clin Chem Lab Med. 2008;46(8):1090-6. doi: 10.1515/CCLM.2008.227.

Abstract

BACKGROUND

Cytochrome P450 (CYP) and glutathione S-transferase (GST) gene variants have been intensively investigated for their implication in the development of different neoplasms.

METHODS

In the present study, we analyzed genetic polymorphisms of CYP1A1, GSTM1, GSTP1, and GSTT1 in 127 head and neck cancer patients and 151 hospital controls.

RESULTS

No significant increase in risk in patients with the GSTM1 null genotype (OR=1.52, 95% CI: 0.93-2.49) or CYP1A1 462Val alleles (OR=1.60, 95% CI: 0.73-3.52) or GSTP1 105Val alleles (OR=0.97, 95% CI: 0.59-1.58) was observed. The GSTT1 null genotype was found in 30.5% of the controls and 21.3% of the head and neck cancer patients (p=0.15). The estimated head and neck cancer risk for the combination of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with either GSTP1 Ile105Val or Val105Val genotype (OR=2.89, 95% CI: 0.71-11.71) and for the combination of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with GSTT1 null genotype (OR=2.62, 95% CI: 0.64-10.85) suggested the absence of the modifying effect of combined variant alleles on head and neck cancer susceptibility. The joint effect of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with GSTM1 null genotype significantly increased the risk of head and neck cancer (OR=7.15, 95% CI: 1.49-34.32).

CONCLUSIONS

Our findings corroborate metabolic genes interactions, especially for CYP1A1 462Val alleles and GSTM1 homozygous deletion, in the development of head and neck cancer in the investigated population groups in Poland.

摘要

背景

细胞色素P450(CYP)和谷胱甘肽S-转移酶(GST)基因变异对不同肿瘤发生发展的影响已得到深入研究。

方法

在本研究中,我们分析了127例头颈癌患者和151例医院对照者中CYP1A1、GSTM1、GSTP1和GSTT1的基因多态性。

结果

未观察到GSTM1无效基因型患者(比值比=1.52,95%可信区间:0.93 - 2.49)、CYP1A1 462Val等位基因患者(比值比=1.60,95%可信区间:0.73 - 3.52)或GSTP1 105Val等位基因患者(比值比=0.97,95%可信区间:0.59 - 1.58)的风险显著增加。在30.5%的对照者和21.3%的头颈癌患者中发现了GSTT1无效基因型(p = 0.15)。CYP1A1 Ile462Val或CYP1A1 Val462Val基因型与GSTP1 Ile105Val或Val105Val基因型组合(比值比=2.89,95%可信区间:0.71 - 11.71)以及CYP1A1 Ile462Val或CYP1A1 Val462Val基因型与GSTT1无效基因型组合(比值比=2.62,95%可信区间:0.64 - 10.85)的头颈癌风险估计表明,联合变异等位基因对头颈癌易感性不存在修饰作用。CYP1A1 Ile462Val或CYP1A1 Val462Val基因型与GSTM1无效基因型的联合作用显著增加了头颈癌风险(比值比=7.15,95%可信区间:1.49 - 34.32)。

结论

我们的研究结果证实了在波兰被调查人群组中,代谢基因相互作用,特别是CYP1A1 462Val等位基因和GSTM1纯合缺失,在头颈癌发生发展中的作用。

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