Carcinogenesis Advance Access originally published online on February 16, 2007
Carcinogenesis 2007 28(7):1455-1462; doi:10.1093/carcin/bgm038
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Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator
Cancer Research Institute, Advanced Center for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai 410 208, India
1 BTIS Advanced Center for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai 410 208, India
2 Zoology Department, University of Pune, Ganesh Khind, Pune 411007, India
* To whom correspondence should be addressed. Tel: +91 22 2740 5000, Ext 5049; Fax: +91 22 27405085/5058; Email: mmahimkar{at}actrec.gov.in
Oral cancer is the leading cancer type among Southeast Asian men and is causally associated with the use of tobacco. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene–environment interactions and hence contribute to the high degree of variance in individual susceptibility to cancer risk. This study investigates the role of polymorphisms at CYP1A1, GSTM1 and GSTT1 to oral squamous cell carcinoma (OSCC) in a case–control study involving 155 patients with precancerous lesions, 458 cancer patients and 729 age and habit-matched controls. Genotypes at these loci were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism performed on genomic DNA extracted from peripheral blood lymphocytes. Risk to oral cancer was estimated among different tobacco exposure groups and doses using logistic regression analysis. GSTM1 null genotype conferred 1.29-fold increased risk [95% confidence interval (CI), 1.04–1.65] to OSCC. GSTT1 null genotype, however, conferred 0.57 times reduced risk to OSCC (95% CI, 0.39–0.83), specifically among tobacco chewers (odds ratio 0.27; 95% CI, 0.14–0.53). This risk was further reduced to 0.13 times (95% CI, 0.04–0.46) with increase in lifetime exposure to tobacco. We also investigated risk conferred by these genotypes at two different intra-oral sites, buccal mucosa and tongue. We found increased susceptibility to buccal mucosa cancer among individuals carrying these genetic markers. These results support the finding that GSTM1 null genotype is a risk factor to OSCC among Indian tobacco habits; GSTT1 null genotype, however, emerged as a protective factor.
Abbreviations: CI, confidence interval; CYP, cytochrome p450; GSH, glutathione; GST, glutathione S-transferase; OR, odds ratio; OSCC, oral squamous cell carcinoma; PAH, polycyclic aromatic hydrocarbon; PCL, precancerous lesion; PCR, polymerase chain reaction; SCE, sister chromatid exchange
Received October 18, 2006; revised February 8, 2007; accepted February 11, 2007.
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