Functional polymorphisms of the cyclooxygenase (PTGS2) gene and risk for gallbladder cancer in a North Indian population.

BACKGROUND

Cyclooxygenase-2 (PTGS2) overexpression has been implicated in various cancers. We aimed to evaluate the role of PTGS2 -1195G>A [reference sequence (rs) 689466], -765G>C (rs20417) and +8473T>C (rs5275) polymorphisms in conferring interindividual susceptibility to gallbladder cancer.

METHODS

The study included 167 gallbladder cancer cases and 184 controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Risk was estimated using unconditional logistic regression.

RESULTS

Significant risk was observed in the presence of PTGS2 -1195GA (P=0.006; odds ratio=2.00; 95% confidence interval=1.2-3.3) and AA genotypes (P=0.050; odds ratio=2.98; 95% confidence interval=1.0-8.9). Combined risk due to GA+AA genotypes was 2.12 (P=0.002; 95% confidence interval=1.3-3.3; P-trend=0.001). Sub-grouping showed a risk due to the PTGS2 -1195(GA+AA) genotype in males (P=0.007; odds ratio=2.97; 95% confidence interval=1.3-6.5), patients without gallstones (P=0.001; odds ratio=2.53; 95% confidence interval=1.4-4.7) and with late-onset gallbladder cancer (P=0.012; odds ratio=1.99; 95% confidence interval=1.1-3.4). Gallbladder cancer patients who used tobacco were at increased risk in the presence of the PTGS2 -765GC genotype (P=0.018; odds ratio=2.96; 95% confidence interval=1.2-7.2).

CONCLUSIONS

An association of PTGS2 -1195G>A polymorphism with gallbladder cancer, particularly in patients without gallstones, suggests a direct role of PTGS2 in cancer development.