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