Role of GSTM1 and GSTT1 Polymorphism: Susceptibility to Oral Submucous Fibrosis in the North Indian Population

Agrawal, Deepika; Gupta, Shalini; Agarwal, Devisha; Gupta, O. P.; Agarwal, Mohit

doi:10.1159/000318533

Cited by 22 publications

(11 citation statements)

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“…Although a meta-analysis of 19 studies reported no association between the GSTM1-null genotype and oral and pharyngeal cancers [18], 2 recent metaanalyses of more than 27 case-control studies suggested that the GSTM1-null genotype was associated with a higher risk of oral cancer in Asians but not Caucasians [19,20]. For OPMD, 5 studies reported an increased risk [27,[35][36][37][38], and 5 showed no association [32][33][34]39,40]. In this study, the GSTM1null genotype was a risk factor for OPMD (mainly for leukoplakia), especially for heavy smokers.…”

Section: Discussionmentioning

confidence: 99%

“…Activation overexpression or detoxification failure of metabolizing enzymes for chemical carcinogens may increase cancer risk. Although no study has examined the risk conferred by the combination of multiple metabolizing genes, 3 studies on gene-gene interactions have shown that the simultaneous presence of both GSTM1 and GSTT1 deletions is associated with an increased risk of developing oral leukoplakia [27,35,38]. These findings demonstrate that the simultaneous presence of more unfavorable genotypes of xenobiotic-metabolizing genes may increase susceptibility to OPMD.…”

Section: Discussionmentioning

confidence: 99%

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Interactions between Cigarette Smoking and Polymorphisms of Xenobiotic-Metabolizing Genes: The Risk of Oral Leukoplakia

Sung

Tsai

et al. 2013

Disease Markers

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Background: This case-control study investigates the role of xenobiotic-metabolizing genes, including glutathione S-transferases (GSTs) and cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), in the susceptibility to oral potentially malignant disorders (OPMDs).Methods: The genotypes of GSTM1, GSTT1, GSTP1, CYP1A1∗2C, and CYP2E1 PstI/RsaI polymorphisms were determined for 217 OPMD cases and 492 age- and sex-matched controls from a Taiwanese penitentiary.Results: Compared to the GSTM1-present genotype, the GSTM1-null genotype was significantly associated with increased risk of leukoplakia (odds ratio [OR]=1.46, 95% l [CI]=1.01–2.10). Similarly, compared to the CYP1A1∗2C A/G+G/G genotype, the CYP1A1∗2C A/A genotype was significantly associated with increased risk of leukoplakia (OR=1.64, 95% CI=1.12–2.40), particularly for smokers consuming > 13 pack-years of cigarettes (OR=2.40, 95% CI=1.40–4.11) (Interaction P=0.039). In addition, participants with 4–5 risk genotypes (OR > 1) experienced higher risks for leukoplakia than those with 0-1 risk genotypes (OR=3.19, 95% CI=1.65–6.15) (Trend test P=0.001).Conclusions: Our findings suggest that the CYP1A1∗2C A/A genotype may increase the risk of leukoplakia, especially for heavy smokers. Xenobiotic-metabolizing genes may simultaneously modulate this disease risk. These observations require further confirmation with larger samples.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interactions between Cigarette Smoking and Polymorphisms of Xenobiotic-Metabolizing Genes: The Risk of Oral Leukoplakia

Sung

Tsai

et al. 2013

Disease Markers

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“…Altered molecular expressions might be potential markers for a diagnosis and prognosis of OSCC (7). The susceptibility of an individual to oral cancer is mediated by genetic and environmental factors (3,8). Epigenetics is another major player in multistep carcinogenesis of oral cancers (4).…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase 8 as a novel therapeutic target in oral squamous cell carcinoma

Ahn

Yoon

2016

Oncology Reports

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The overexpression of histone deacetylases (HDACs) has been observed in many cancers and inhibition of specific HDAC has emerged as a new target for cancer therapy. The present study examined the expression of HDAC8 and the inhibitory effect of HDAC8 in oral squamous cell carcinoma (OSCC). The expression of HDAC8 was measured in human OSCC tissues and OSCC cell lines using immunohistochemistry and immunoblotting. HDAC8 was knocked down in OSCC cells by transfection with HDAC8 siRNAs and cell proliferation was quantified. Apoptosis and autophagy were measured using flow cytometry and immunoblotting. HDAC8 were overexpressed in OSCC tissues and OSCC cells, mainly localized in the cytoplasm. HDAC8 siRNAs effectively reduced the level of HDAC8 expression and HDAC8 silencing significantly inhibited the proliferation of OSCC cells. HDAC8 knockdown induced apoptotic cell death through caspases activation and pro-survival autophagy in OSCC cells. Combination with HDAC silencing and autophagy inhibition enhanced cell death by increasing apoptosis in OSCC cells. This study suggests that inhibition of HDAC8 might become a novel therapeutic strategy for OSCC.

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“…Furthermore, the concomitant use of betel quid leads to 50-fold increase in reactive oxygen species generation (ROS) [12], [13]. A structural deletion in these genes represents a null genotype and has been associated with an increased risk to oral cancer [14].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number and Risk of Oral Cancer: A Report from Northeast India

et al. 2013

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BackgroundOral squamous cell carcinoma (OSCC) is the sixth most common cancer globally. Tobacco consumption and HPV infection, both are the major risk factor for the development of oral cancer and causes mitochondrial dysfunction. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene–environment interactions and hence contributing to the individual susceptibility to cancer. Here, we have investigated the association of tobacco - betel quid chewing, HPV infection, GSTM1-GSTT1 null genotypes, and tumour stages with mitochondrial DNA (mtDNA) content variation in oral cancer patients.Methodology/Principal FindingsThe study comprised of 124 cases of OSCC and 140 control subjects to PCR based detection was done for high-risk HPV using a consensus primer and multiplex PCR was done for detection of GSTM1-GSTT1 polymorphism. A comparative ΔCt method was used for determination of mtDNA content. The risk of OSCC increased with the ceased mtDNA copy number (Ptrend = 0.003). The association between mtDNA copy number and OSCC risk was evident among tobacco – betel quid chewers rather than tobacco – betel quid non chewers; the interaction between mtDNA copy number and tobacco – betel quid was significant (P = 0.0005). Significant difference was observed between GSTM1 - GSTT1 null genotypes (P = 0.04, P = 0.001 respectively) and HPV infection (P<0.001) with mtDNA content variation in cases and controls. Positive correlation was found with decrease in mtDNA content with the increase in tumour stages (P<0.001). We are reporting for the first time the association of HPV infection and GSTM1-GSTT1 null genotypes with mtDNA content in OSCC.ConclusionOur results indicate that the mtDNA content in tumour tissues changes with tumour stage and tobacco-betel quid chewing habits while low levels of mtDNA content suggests invasive thereby serving as a biomarker in detection of OSCC.

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Role of GSTM1 and GSTT1 Polymorphism: Susceptibility to Oral Submucous Fibrosis in the North Indian Population

Cited by 22 publications

References 60 publications

Interactions between Cigarette Smoking and Polymorphisms of Xenobiotic-Metabolizing Genes: The Risk of Oral Leukoplakia

Interactions between Cigarette Smoking and Polymorphisms of Xenobiotic-Metabolizing Genes: The Risk of Oral Leukoplakia

Histone deacetylase 8 as a novel therapeutic target in oral squamous cell carcinoma

Mitochondrial DNA Copy Number and Risk of Oral Cancer: A Report from Northeast India

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