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.
Pu
Xia
X
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Lippman
Scott M
SM
Yang
Hushan
H
Lee
J Jack
JJ
Wu
Xifeng
X
D000328:Adult; D000428:Alcohol Drinking; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
D051546:Cyclooxygenase 2