一项关于谷胱甘肽转移酶及功能相关多态性与原发性成人脑肿瘤风险的国际病例对照研究。

An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors.

作者信息

Schwartzbaum Judith A, Ahlbom Anders, Lönn Stefan, Warholm Margareta, Rannug Agneta, Auvinen Anssi, Christensen Helle Collatz, Henriksson Roger, Johansen Christoffer, Lindholm Carita, Malmer Beatrice, Salminen Tiina, Schoemaker Minouk J, Swerdlow Anthony J, Feychting Maria

机构信息

Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Starling-Loving Hall, 320 W. Tenth Avenue, Columbus, OH 43210, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):559-65. doi: 10.1158/1055-9965.EPI-06-0918.

DOI:10.1158/1055-9965.EPI-06-0918

PMID:17372252

Abstract

BACKGROUND

Glutathione transferases (GST) detoxify environmental and endogenous compounds and levels of two polymorphic GST proteins, GSTM3 and GSTP1, are high in the brain. Previous studies of GSTM3 and GSTP1 polymorphisms and adult brain tumor risk have produced inconsistent results, whereas the GSTM3 -63 variant is newly identified and, therefore, has not yet been studied in this context. We therefore examined associations between GSTM3 -63, GSTM3 *A/*B, GSTP1 105, and GSTP1 114 variants and adult brain tumor risk and the interaction of the effects of these same polymorphisms with cigarette smoking. In addition, the enzymes NQO1 and CYP1A1 alter susceptibility to oxidative brain damage. Because there is less previous evidence for a role of NQO1, CYP1A1, GSTM1, and GSTT1 variants, we restricted analysis of these variants to a small preliminary study.

METHODS

We genotyped DNA collected for an international population-based case-control study of 725 glioma cases, 329 of which were glioblastoma cases, 546 meningioma cases and 1,612 controls. Study participants were residents of Sweden, southeast England, Denmark, and Finland.

RESULTS

We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking.

CONCLUSIONS

Overall, we observed no strong evidence for an association between GST or related enzyme polymorphisms and adult brain tumor risk.

摘要

背景

谷胱甘肽转移酶（GST）可使环境化合物和内源性化合物解毒，两种多态性GST蛋白GSTM3和GSTP1在大脑中的水平较高。先前关于GSTM3和GSTP1多态性与成人大脑肿瘤风险的研究结果并不一致，而GSTM3 -63变体是新发现的，因此尚未在此背景下进行研究。因此，我们研究了GSTM3 -63、GSTM3 *A/*B、GSTP1 105和GSTP1 114变体与成人大脑肿瘤风险之间的关联，以及这些相同多态性的作用与吸烟之间的相互作用。此外，NQO1和CYP1A1酶会改变对氧化性脑损伤的易感性。由于之前关于NQO1、CYP1A1、GSTM1和GSTT1变体作用的证据较少，我们将这些变体的分析限制在一项小型初步研究中。

方法

我们对为一项基于国际人群的病例对照研究收集的DNA进行基因分型，该研究包括725例胶质瘤病例（其中329例为胶质母细胞瘤病例）、546例脑膜瘤病例和1612例对照。研究参与者为瑞典、英格兰东南部、丹麦和芬兰的居民。

结果

我们发现GSTM3、GSTP1、NQO1、CYP1A1、GSTM1或GSTT1多态性与成人大脑肿瘤风险之间无关联，可能的例外是G-C（Val-Ala）GSTP1 105/114单倍型与胶质瘤之间存在微弱关联[比值比（OR）为0.73；95%置信区间（95%CI）为0.54, 0.99]，GSTM3或GSTP1多态性的作用与吸烟之间也没有相互作用。