Cyclooxygenase-2 gene polymorphisms reduce the risk of oral premalignant lesions

BACKGROUND: Oral premalignant lesions (OPLs) have the potential to transform into malignant oral cancers. Overexpression of the cyclooxygenase-2 gene (COX-2) is observed frequently in OPLs and oral cancers, suggesting that this gene may play an important role in the progression of oral cancer. Single- nucleotide polymorphisms of COX-2 have been associated with the risk of multiple cancers; however, to date, their effects on OPL susceptibility have not been evaluated sufficiently. METHODS: The authors conducted a case-control study that included 147 patients with OPL and a group of 147 healthy, matched controls. The effects of 3 potentially functional COX-2 polymorphisms on the risk of OPL were evaluated: the -765 G→C polymorphism (rs20417), the exon 10 +837 T→C polymorphism (rs5275), and the exon 10 -90 C→T polymorphism (rs689470). RESULTS: The variant-containing genotypes of COX-2 exon 10 +837T→C variant were associated with a significantly reduced risk of OPL (odds ratio [OR], 0.48; 95% confidence interval [95% CI], 0.28-0.80). This protective effect also was significant in men, younger individuals, ever smokers, and ever drinkers. Consistently, a common halotype WMW (in the following order: -765G→C, exon 10 +837T→C, and exon 10 -90C→T; w, widetype; M, variable allele), and a common diplotype (WWW/WMW) that contained the variant allele of exon 10 +837T→C, both were associated with a reduced risk of OPL (WMW: OR, 0.55; 95% CI, 0.33-0.93; WWW/WMW: OR, 0.44; 95% CI, 0.22-0.89). In addition, using never smokers with the variant-containing genotypes as the reference group, interaction effects were observed between specific COX-2 variants and tobacco smoking in the modulation of OPL risk. CONCLUSIONS: Overall, the current results provided the first epidemiologic evidence indicating that potentially functional polymorphisms of the COX-2 gene may have an impact on individual susceptibility to OPLs.