Carcinogenesis, Vol. 20, No. 5, 743-748,
May 1999
© 1999 Oxford University Press
Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany and
1 Community Oncology, Regional Cancer Centre, Trivandrum, India
Oral cancer is the most common cancer in males and third most common in females in India, the main causative agent being the use of chewing tobacco with or without betel quid (BQ). However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In this study, the prevalence of GSTM1 and GSTT1 null genotypes (GSTM1*2 and GSTT1*2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leukoplakia patients and exfoliated cells from 82 healthy controls both of Indian ethnicity were analysed. GSTM1*1 (active) was present in 83% and GSTT1*1 (active) was present in 78% of all control subjects, while prevalence of GSTM1*2 and GSTT1*2 null genotypes was significantly higher among oral leukoplakia cases. The prevalence of GSTM1*2 in leukoplakia cases was 81.6% compared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (CI), 10–47] and GSTT1*2 was 75.5% in the cases versus 22% in controls (OR, 11; 95% CI, 5–22). Combined null genotypes of GSTM1 and GSTT1 prevailed in 60.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive oxygen species, lipid peroxidation products and tobacco-derived carcinogens that have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genotypes of both GSTM1 and GSTT1 increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic population.
Abbreviations: BQ, betel quid; CI, confidence interval; GST, glutathione S-transferase; HNSCC, head and neck squamous cell carcinoma; LOH, loss of heterozygosity; OR, odds ratio; PAHs, polycyclic aromatic hydrocarbons; ROS, reactive oxygen species; TSNA, tobacco-specific nitrosamines.
2 To whom correspondence should be addressed Email: h.bartsch{at}dkfz-heidelberg.de
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Anantharaman, P. M. Chaubal, S. Kannan, R. A. Bhisey, and M. B. Mahimkar Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator Carcinogenesis, July 1, 2007; 28(7): 1455 - 1462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Majumder, N. Sikdar, R. R. Paul, and B. Roy Increased Risk of Oral Leukoplakia and Cancer Among Mixed Tobacco Users Carrying XRCC1 Variant Haplotypes and Cancer Among Smokers Carrying Two Risk Genotypes: One on Each of Two Loci, GSTM3 and XRCC1 (Codon 280) Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2106 - 2112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lee, N. J. Hodges, and J. K. Chipman Interindividual Variability in Response to Sodium Dichromate-Induced Oxidative DNA Damage: Role of the Ser326Cys Polymorphism in the DNA-Repair Protein of 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine DNA Glycosylase 1 Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 497 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Nair, H. Bartsch, and J. Nair Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms Mutagenesis, July 1, 2004; 19(4): 251 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Buch, P. N. Notani, and R. A. Bhisey Polymorphism at GSTM1, GSTM3 and GSTT1 gene loci and susceptibility to oral cancer in an Indian population Carcinogenesis, May 1, 2002; 23(5): 803 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Topcu, I. Chiba, M. Fujieda, T. Shibata, N. Ariyoshi, H. Yamazaki, F. Sevgican, M. Muthumala, H. Kobayashi, and T. Kamataki CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka Carcinogenesis, April 1, 2002; 23(4): 595 - 598. [Abstract] [Full Text] [PDF]
|
|