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Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population.
Eur J Cancer. 2007 Dec; 43(18):2698-706.EJ

Abstract

The glutathione-S-transferase (GST) genes are involved in the detoxification of various carcinogens that increase the risk to upper aerodigestive tract (UADT) cancers. In the present study, 408 unrelated histopathologically confirmed cases and 220 population based controls, matched by age and gender, which belonged to the Tamilian population of south India were genotyped for polymorphisms in GSTM1, GSTT1 and GSTP1 using polymerase chain reaction (PCR) based methods. The multivariate logistic regression analyses demonstrated that GSTT1 null genotype was significantly associated with increased risk for UADT cancers (odds ratio (OR) 2.5; 95% confidence intervals (CIs) 1.3-4.7). The combined effects of GST genes have shown that concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR 4.6; 95% CI 1.3-15.6), while GSTT1 null genotype along with GSTP1 polymorphic variants further increased the cancer risk (OR 5.3; 95% CI 2.0-13.6). The most remarkable risk was seen among individuals carrying GSTM1 null, GSTT1 null genotypes and GSTP1 polymorphic variants (OR 7.8; 95% CI 1.0-61.0). Tobacco chewers carrying GSTM1 null genotype had an enhanced risk for UADT cancers. An enhanced risk among tobacco chewers and alcoholics (regular) was noted in individuals with GSTT1 null genotype. Similarly, a significant interaction was observed among smokers (>40 pack-year (PY)) and tobacco chewers carrying GSTP1 mutant genotypes. Although the null genotype of GSTT1 is a strong predisposing risk factor for UADT cancers, we conclude that the significant gene-gene and gene-environment interactions of GST genes may confer a substantial risk to UADT cancers in the Tamilian population of south India.

Authors+Show Affiliations

Department of Pharmacology, Jawaharlal Institute of Post-Graduate Medical Education and Research, Pondicherry 605 006, India. soyasoya@rediffmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17707637

Citation

Soya, S S., et al. "Genetic Polymorphisms of glutathione-S-transferase Genes (GSTM1, GSTT1 and GSTP1) and Upper Aerodigestive Tract Cancer Risk Among Smokers, Tobacco Chewers and Alcoholics in an Indian Population." European Journal of Cancer (Oxford, England : 1990), vol. 43, no. 18, 2007, pp. 2698-706.
Soya SS, Vinod T, Reddy KS, et al. Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population. Eur J Cancer. 2007;43(18):2698-706.
Soya, S. S., Vinod, T., Reddy, K. S., Gopalakrishnan, S., & Adithan, C. (2007). Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population. European Journal of Cancer (Oxford, England : 1990), 43(18), 2698-706.
Soya SS, et al. Genetic Polymorphisms of glutathione-S-transferase Genes (GSTM1, GSTT1 and GSTP1) and Upper Aerodigestive Tract Cancer Risk Among Smokers, Tobacco Chewers and Alcoholics in an Indian Population. Eur J Cancer. 2007;43(18):2698-706. PubMed PMID: 17707637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population. AU - Soya,S S, AU - Vinod,T, AU - Reddy,K S, AU - Gopalakrishnan,S, AU - Adithan,C, Y1 - 2007/08/17/ PY - 2007/04/25/received PY - 2007/06/30/revised PY - 2007/07/04/accepted PY - 2007/8/21/pubmed PY - 2008/3/11/medline PY - 2007/8/21/entrez SP - 2698 EP - 706 JF - European journal of cancer (Oxford, England : 1990) JO - Eur J Cancer VL - 43 IS - 18 N2 - The glutathione-S-transferase (GST) genes are involved in the detoxification of various carcinogens that increase the risk to upper aerodigestive tract (UADT) cancers. In the present study, 408 unrelated histopathologically confirmed cases and 220 population based controls, matched by age and gender, which belonged to the Tamilian population of south India were genotyped for polymorphisms in GSTM1, GSTT1 and GSTP1 using polymerase chain reaction (PCR) based methods. The multivariate logistic regression analyses demonstrated that GSTT1 null genotype was significantly associated with increased risk for UADT cancers (odds ratio (OR) 2.5; 95% confidence intervals (CIs) 1.3-4.7). The combined effects of GST genes have shown that concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR 4.6; 95% CI 1.3-15.6), while GSTT1 null genotype along with GSTP1 polymorphic variants further increased the cancer risk (OR 5.3; 95% CI 2.0-13.6). The most remarkable risk was seen among individuals carrying GSTM1 null, GSTT1 null genotypes and GSTP1 polymorphic variants (OR 7.8; 95% CI 1.0-61.0). Tobacco chewers carrying GSTM1 null genotype had an enhanced risk for UADT cancers. An enhanced risk among tobacco chewers and alcoholics (regular) was noted in individuals with GSTT1 null genotype. Similarly, a significant interaction was observed among smokers (>40 pack-year (PY)) and tobacco chewers carrying GSTP1 mutant genotypes. Although the null genotype of GSTT1 is a strong predisposing risk factor for UADT cancers, we conclude that the significant gene-gene and gene-environment interactions of GST genes may confer a substantial risk to UADT cancers in the Tamilian population of south India. SN - 0959-8049 UR - https://www.unboundmedicine.com/medline/citation/17707637/Genetic_polymorphisms_of_glutathione_S_transferase_genes__GSTM1_GSTT1_and_GSTP1__and_upper_aerodigestive_tract_cancer_risk_among_smokers_tobacco_chewers_and_alcoholics_in_an_Indian_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0959-8049(07)00529-1 DB - PRIME DP - Unbound Medicine ER -