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

Coutinho, Paula; Sandim, Vanessa; Oliveira, Juraci Alves de; Alves, Gilda; Hatagima, Ana

doi:10.4238/vol9-1gmr753

Cited by 11 publications

(9 citation statements)

References 16 publications

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“…In addition, a study of 78 patients and 374 controls did not reveal an association between GST polymorphisms and primary glioma risk in Brazilians (Coutinho et al, 2010). In this study, GSTM1 deletion was not significantly correlated (P = 0.19) with the occurrence of malignant glioma in adult Brazilians.…”

Section: Discussioncontrasting

confidence: 73%

Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy

Silva

Fonseca²,

Moura-Neto³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) are critical enzymes for detoxification of endogenous and environmental carcinogens. Constitutive GST gene polymorphisms may be associated with increased risk for cancer development. We made an explorative study of a Brazilian population with malignant glioma to determine whether GSTM1 and GSTT1 genetic polymorphisms influence the response to intranasal administration of perillyl alcohol and the survival rate. Patients were stratified into groups according to clinical presentation, tumor classification, and tumor location. Circulating DNA was extracted from blood plasma or serum, and genotypes were detected by multiplex PCR. The cohort included 95 patients with recurrent malignant glioma included in a Phase I/II clinical trial with perillyl alcohol and 100 matched healthy control subjects. GSTM1 frequency was similar in patients with glioma (44%) and healthy controls (54%), but GSTT1 deletion was found in 11.5% patients, contrasting with 36% in controls. A longer survival rate was associated with a lack of GSTM1 deletion (31 weeks) and a deletion for GSTT1 (28 weeks). A poor survival rate was associated with GSTM1 deletion (23 weeks) and with a lack of a GSTT1 deletion (19 weeks). A significantly lower frequency of GSTT1 deletion in glioma patients compared to healthy controls indicates that GSTT1 deletion may exert a protective role against gliomagenesis, influence therapeutic response to intranasal perillyl alcohol treatment, and increase overall survival, especially considering tumor topography.

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Section: Discussioncontrasting

confidence: 73%

Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy

Silva

Fonseca²,

Moura-Neto³

et al. 2013

Genet. Mol. Res.

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“…Number of female smokers was very less, so it was not possible to compare the results between both the genders. No significant differences were observed between smokers and non-smokers, alcoholic and non-alcoholic individuals, tobacco chewers and non-chewers, carrying homozygous GSTM1/GSTT1/GSTM1T1 null genotype (p>0.05) ( Anantharaman, 2007;Buch et al, 2002;Nair et al, 1999 South Indians c 1744 485 (27.8)** 242 (13.9) 136 (7.8) Naveen et al, 2004;Samson, 2007;Shehnaz et al, 2011;Sreelekha et al, 2001;Suneetha, 2011;Vettriselvi et al, 2006;Vijayalakshmi et al, 2005 East Indians d 67 18(27.0) 9 (13.0) Sikdar et al, 2005 Central Indians e 282 99 (35.1) 37 (13.0) Devi et al, 2008 North Nair et al, 1999;Singh et al, 2009 Blacks b 3008 960 (31.9) 744 (24.9)* 298 (9.9)* Adams et al, 2003;Benzamin et al, 2011;Coutinho et al, 2010;Dandara et al, 2002;Lavender et al, 2009;Masimirembwa et al, 1998;Millikan et al, 2000;Rossini et al, 2002 Caucasians c 2674 1064/2232 (47.7)* 448/2674 (16.7) 31 (9.3) Amer et al, 2011;Baranova et al, 1997;Chen et al, 1996;D'Alo et al, 2004;Gsur et al, 2001;Kargas et al, 2003;Millikan et al, 2000;Mitrunen et al, 2001;Steinhoff et al, 2000;Welfare et al, 1999 Asians 1). The frequency distribution of GSTM1 and GSTT1 alleles were compared between different states of India and other populations all over the world (Table 2 and 3).…”

Section: Resultsmentioning

confidence: 99%

Genetic Polymorphisms of GSTM1 and GSTT1 Genes in Delhi and Comparison with other Indian and Global Populations

Sharma¹,

Pandey²,

Sardana³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an array of environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to interindividual variation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphisms were analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequency of individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and 54(10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1simultaneously. The studied population was compared with reported frequencies from other neighbouring state populations, as well as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygous null GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. The frequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believe that due to large number of individuals in this study, our results are reliable estimates of the frequencies of the GSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining to susceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.

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“…Therefore, based on the latest statistics from GST-related studies after 2005, we expect further studies can involve more samples detected by different GST genotypes simultaneously in order to find out whether there were synergy effect among them. A third potentially important finding was that, in our assessment of the association between a GSTT1-null genotype and adults with gliomas, two independent studies by Coutinho et al (2010) and Ezer et al (2002) with weight contributions of 7.82% and 8.39% respectively, were statistically analyzed to determine that patients who carried the GSTT1 null genotype had no increased risk of developing gliomas (Figure 6). In addition, a similar phenomenon was not observed in the GSTM1 and GSTP1 polymorphism analysis.…”

Section: Discussionmentioning

confidence: 99%

“…As shown in Figure 6, sensitivity analyses of GST polymorphisms indicated that two independent studies by Coutinho et al (2010) and Ezer et al (2002), with weight contributions of 7.82% and 8.39%, respectively, were the main origin of the lack of significance in the analysis of association between a GSTT1-null genotype and adult gliomas. If these two studies were excluded, an association between a GSTT1-null genotype and glioma risk would be observed (pooled OR, 1.415; 95% CI, 1.121-1.786; P heterogeneity, 0.076; I square, 45.4%).…”

Section: Sensitivity Analysismentioning

confidence: 96%

“…Recently, many studies of adult brain tumors have reported that an association exists between susceptibility to brain tumors and the presence of GST variants in patients (Elexpuru et al,1995;Hand et al, 1996;Wiencke et al, 1997;Trizna et al, 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;Coutinho et al, 2010;Custódio et al, 2010). In contrast, Lai et al (2005) conducted a meta-analysis of the association between genetic polymorphisms of GSTs and the risk of adult brain tumors (Lai et al, 2005), and their results did not suggest any relationship between those two.…”

Section: An Updated Pooled Analysis Of Glutathione S-transferase Genomentioning

confidence: 99%

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An Updated Pooled Analysis of Glutathione S-transferase Genotype Polymorphisms and Risk of Adult Gliomas

Yao¹,

Ji²,

Gu³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using χ 2 -based Q statistic and the I 2 statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.

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

Cited by 11 publications

References 16 publications

Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy

Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy

Genetic Polymorphisms of GSTM1 and GSTT1 Genes in Delhi and Comparison with other Indian and Global Populations

An Updated Pooled Analysis of Glutathione S-transferase Genotype Polymorphisms and Risk of Adult Gliomas

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