Ethnic Differences in Distributions of GSTM1 and GSTT1 Homozygous &amp;quot;Null&amp;quot; Genotypes in India

Roy, Bidyut; Majumder, Partha P.; Dey, Badal; Chakraborty, Madan; Banerjee, Sumilan; Roy, Mervyn; Mukherjee, N.; Sil, Samir Kumar

doi:10.1353/hub.2001.0040

Cited by 30 publications

(18 citation statements)

References 15 publications

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“…The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are surprisingly high in most human populations, and noticeable differences between ethnic groups exist. Nelson et al (1995) reported that the GSTM1 null or deletion genotype was present in about 50% of Caucasians, 33% of African Americans and 45% of Japanese, which is in accordance with the studies of Roy et al (2001). Similar results were obtained in a few other studies (Persson et al 1999;Chan et al 2004).…”

Section: Discussionsupporting

confidence: 82%

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

et al. 2005

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Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. As the incidence of lung cancer is known to differ according to ethnicity, we have conducted a case-control study of 146 South Indian lung cancer patients along with 146 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of lung cancer in our population. The current weight of evidence from our study indicated that the frequency of CYP1A1 MspI homozygous variant alleles was significantly higher in cases (OR=3.178). We observed a considerable difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=2.472, 95% CI: 1.191-5.094, P=0.014). There was no relative risk in GSTM1 null genotype when analysed singly (P=0.453). Considering genotype combinations, risk of lung cancer increased remarkably significantly in individuals having one variant allele of CYP1A1, GSTM1, or GSTT1, suggesting gene-gene interactions. Rare genotypic combinations (such as CYP1A1 wild GSTM1 or GSTT1 either null; CYP1A1 variant both GSTM1 and GSTT1 present; CYP1A1 variant GSTM1 or GSTT1 either null), were at higher risk compared to the reference group. Moreover, patients who had smoked <20 pack years and harboured the CYP1A1 variant allele or the GSTT1 null genotype also had a significant risk of lung cancer. Hence our study-the first to analyse a South Indian population-suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.

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Section: Discussionsupporting

confidence: 82%

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

et al. 2005

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“…The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are surprisingly high in most human populations, and noticeable differences between ethnic groups exist (Nelson et al, 1995). GSTM1 null genotype was present in about 50% of Caucasians, 33% of African Americans and 45% of Japanese (Persson et al, 1999;Roy et al, 2001;Chan-Yeung et al, 2004) and various studies have shown an increased Lung cancer risk for GSTM1 null genotype independent of ethnic background (Chen et al, 1996;Gao and Zhang, 1999). GSTT1 null genotype was present in 64% of Chinese, 60% of Koreans, 28% of Caucasians and 22% of African Americans (Nelson et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population

Shukla

Tilak²,

Kumar³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.

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“…The polymorphic form of GSTT1 results in a partial or complete deletion of the gene, which has been found to cause deficiency in enzyme activity ( Hallier et al, 1993). Varied results have been reported on the GSTM1 and GSTT1 null genotype and its association to CML in different ethnic populations ( Weber , 1999;Roy et al, 2001;Mondal et al, 2005;Lourenco et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

Bhat

Bhat²,

Wani³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelated non-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

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Ethnic Differences in Distributions of GSTM1 and GSTT1 Homozygous "Null" Genotypes in India

Cited by 30 publications

References 15 publications

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population

Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

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