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Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India

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Tumor Biology

Abstract

Polymorphisms in glutathione-S-transferases (GSTs), the phase II xenobiotic detoxifying enzymes, have been associated with increased cancer risk. In this study, we assessed the association of functional polymorphisms in GSTM1 and GSTT1 with esophageal cancer in Kashmir, India, an area with a high incidence of esophageal squamous cell carcinoma (ESCC). We analyzed genotypes of GSTM1 and GSTT1 using a multiplex PCR in 492 pairs of ESCC cases and individually matched controls. The associations between polymorphisms in these genes and ESCC risk were examined by conditional logistic regression models adjusted for multiple potential confounders. In addition, the interaction between these genes and several environmental exposures with regard to ESCC risk was assessed. Our results showed an association between the GSTT1 null genotype and ESCC risk (odds ratio (OR) = 1.58; 95 % confidence interval (CI) 1.04–2.39). Although GSTM1 alone was not associated with ESCC risk, individuals with the GSTM1 /GSTT1 + genotype showed an inverse relation with ESCC risk (OR = 0.55; 95 % CI 0.32–0.93), compared to GSTM1 +/GSTT1 + individuals. We found a significant interaction between the GSTT1 and GSTM1 genotypes with regard to ESCC risk (P = 0.001); however, there were no interactions between environmental factors and GSTT1 and GSTM1 genotypes. This study indicates that GSTT1 null genotype is associated with ESCC risk in Kashmiri population. The association between GSTM1 and ESCC risk needs further investigations. Interactions of these genotypes with environmental exposures should be examined in multicentric studies with bigger sample sizes.

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Acknowledgments

This study was supported by Extramural grant of Indian Council of Medical Research (ICMR), New Delhi, under IRIS ID 5/13/37/2007/-NCD-III. The authors are thankful to the consultants and paramedical staff at SKIMS for their precious help during sample collection. The authors are grateful to all the subjects who participated in this study.

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Correspondence to Nazir Ahmad Dar.

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Muzamil Ashraf Makhdoomi and Idrees Ayoub Shah contributed equally.

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Makhdoomi, M.A., Shah, I.A., Bhat, G.A. et al. Association between GSTM1 and GSTT1 polymorphisms and esophageal squamous cell carcinoma: results from a case-control study in Kashmir, India. Tumor Biol. 36, 2613–2619 (2015). https://doi.org/10.1007/s13277-014-2882-0

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