Polymorphisms in COX-2 gene influence prostate cancer susceptibility in a northern Indian cohort

Background and aims: Cyclooxygenase-2 (COX-2) converts arachidonic acid to prostaglandins, which are important mediators of cell proliferation and inflammation. Evidence indicates that COX-2 plays a role in carcinogenesis and that it is overexpressed in prostate tumors. We examined whether sequence variants in the COX-2 gene were associated with prostate cancer (PCa) risk.

Methods: In a hospital-based case/control study, 195 subjects with PCa and 250 healthy controls were investigated for the association of COX-2 -765 G>C (rs20417) and +8473 T>C (rs5275) promoter polymorphism with PCa susceptibility using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.

Result: Variant allele 'C' carriers of COX-2 -765 G>C polymorphism were associated with a 1.7-fold increased risk for PCa (p = 0.016; OR = 1.74). The variant genotype CC of COX-2 +8473 T>C polymorphism was found to be significantly associated with the overall higher risk of PCa (p = 0.045; OR = 1.82). Combined genotype (TC + CC) also demonstrated a 1.5-fold significant risk with PCa (p = 0.040; OR = 1.52). The diplotype C-C was observed to be associated with a significant increase in PCa risk (Bonferroni corrected p value, Pc = 0.004; OR = 4.26). Stratification of cases based on clinical pathological grade of tumors revealed no association with PCa risk.

Conclusions: Our findings suggest COX-2 -765G>C and +8473 T>C polymorphism and diplotype C-C to be a risk factor for PCa. However, further validation in large population-based studies is needed to confirm the finding.