An International Case-Control Study of Glutathione Transferase and Functionally Related Polymorphisms and Risk of Primary Adult Brain Tumors

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; Feychting, Maria

doi:10.1158/1055-9965.epi-06-0918

Cited by 52 publications

(35 citation statements)

References 29 publications

(27 reference statements)

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“…Our results do not show an association of GSTM3 with risk of glioma and corroborate previous studies (Hand et al, 1996;Schwartzbaum et al, 2007). However, a large hospital-based case-control study observed an increased risk of glioma (OR = 2.3; 95%CI = 1.0-5.2) associated with the GSTM3 B/B genotype (De Roos et al, 2006).…”

Section: Discussionsupporting

confidence: 87%

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Lack of association between glutathione S-transferase polymorphisms and primary glioma in a case-control study in Rio de Janeiro

Coutinho

Sandim²,

Oliveira³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. The glutathione S-transferases (GSTs), a family of phase II isozymes, detoxify several carcinogens. Genetic variations in GSTs have been associated with increased risk for cancer due to a heritable deficiency in detoxification pathways for environmental carcinogens. Conflicting findings have been reported about the association between constitutive GST polymorphisms and gliomas in different populations. The present case-control study examined 78 patients with primary glioma and 347 controls from Rio de Janeiro. DNA was isolated from whole blood, and four genetic polymorphisms (GSTM1, GSTM3, GSTT1, and GSTP1) were determined by PCR-RFLP. The distributions of the genotypic frequencies of these polymorphisms did not differ significantly between cases and controls and were as expected by Hardy-Weinberg equilibrium (P > 0.05). Risk analysis did not show an association between GSTs and primary glioma, suggesting that these polymorphisms do not influence the risk of primary glioma, at least in this population in Rio de Janeiro, Brazil.

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Section: Discussionsupporting

confidence: 87%

“…However, Schwartzbaum et al (2007) did not find any association between GSTs polymorphisms and adult brain tumor risk in 725 patients and 1612 controls from Europe. Other studies corroborate these findings (De Roos et al, 2003;Butler et al, 2003;Lanciotti et al, 2005), including the present one.…”

Section: Discussionmentioning

confidence: 74%

Lack of association between glutathione S-transferase polymorphisms and primary glioma in a case-control study in Rio de Janeiro

Coutinho

Sandim²,

Oliveira³

et al. 2010

Genet. Mol. Res.

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“…Very few studies have investigated the GSTs enzymes and risk of developing brain cancer with inconsistent results (Schwartzbaum et al, 2007;Salnikova et al, 2010). In this study we evaluated possible associations between expressional pattern of CYP1A1, GSTP1 and the risk of developing brain tumors.…”

Section: Discussionmentioning

confidence: 99%

Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Wahid¹,

Mahjabeen²,

Baig³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Most of the exogenous and endogenous chemical compounds are metabolized by enzymes of xenobiotic processing pathways, including the phase I cytochrome p450 species. Carcinogens and their metabolites are generally detoxified by phase II enzymes like glutathione-S-transferases (GST). The balance of enzymes determines whether metabolic activation of pro-carcinogens or inactivation of carcinogens occurs. Under certain conditions, deregulated expression of xenobiotic enzymes may also convert endogenous substrates to metabolites that can facilitate DNA adduct formation and ultimately lead to cancer development. In this study, we aimed to test the association between deregulation of metabolizing genes and brain tumorigenesis. The expression profile of metabolizing genes CYP1A1 and GSTP1 was therefore studied in a cohort of 36 brain tumor patients and controls using Western blotting. In a second part of the study we analyzed protein expression of GSTs in the same study cohort by ELISA. CYP1A1 expression was found to be significantly high (p<0.001) in brain tumor as compared to the normal tissues, with ~4 fold (OR=4, 95%CI=0.43-37) increase in some cases. In contrast, the expression of GSTP1 was found to be significantly low in brain tumor tissues as compared to the controls (p<0.02). This down regulation was significantly higher (OR=0.05, 95%CI=0.006-0.51; p<0.007) in certain grades of lesions. Furthermore, GSTs levels were significantly down-regulated (p<0.014) in brain tumor patients compared to controls. Statistically significant decrease in GST levels was observed in the more advanced lesions (III-IV, p<0.005) as compared to the early tissue grades (I-II). Thus, altered expression of these xenobiotic metabolizing genes may be involved in brain tumor development in Pakistani population. Investigation of expression of these genes may provide information not only for the prediction of individual cancer risk but also for the prevention of cancer.

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“…Xiu-Tian Sima 1 , Wei-Ying Zhong 1 , Jian-Gang Liu 2 , Chao You 1 * 1998; Kondratieva et al, 2000;Ezer et al, 2002;De Roos et al, 2003;Wrensch et al, 2004;Pinarbasi et al, 2005;Schwartzbaum et al, 2007;Custodio et al, 2010). However, the results were conflicting.…”

Section: Lack Of Association Between Gstm1 and Gstt1 Polymorphisms Anmentioning

confidence: 99%

Lack of Association Between GSTM1 and GSTT1 Polymorphisms and Brain Tumour Risk

Sima

Zhong²,

Liu³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: Glutathione S-transferases (GSTs) are important enzymes that are involved in detoxification of environmental carcinogens. Molecular epidemiological studies have been conducted to investigate the association between GSTM1 and GSTT1 homozygous deletion polymorphisms and brain tumours but results have been conflicting. The aim of this study was to clarify this problem using a meta-analysis. Methods: A total of 9 records were identified by searching the PubMed and Embase databases. Fixed-and random-effects models were performed to estimate the pooled odds ratios. Results: No significant association was found between the GSTM1 and GSTT1 homozygous deletion polymorphisms and risk of brain tumours, including glioma and meningioma. Similar negative results were also observed in both population-based and hospital-based studies. Conclusion: These findings indicate that the GSTM1 and GSTT1 polymorphisms may not be related to the development of brain tumours.

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An International Case-Control Study of Glutathione Transferase and Functionally Related Polymorphisms and Risk of Primary Adult Brain Tumors

Cited by 52 publications

References 29 publications

Lack of association between glutathione S-transferase polymorphisms and primary glioma in a case-control study in Rio de Janeiro

Lack of association between glutathione S-transferase polymorphisms and primary glioma in a case-control study in Rio de Janeiro

Expression of CYP1A1 and GSTP1 in Human Brain Tumor Tissues in Pakistan

Lack of Association Between GSTM1 and GSTT1 Polymorphisms and Brain Tumour Risk

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