Direct Sequencing of Cyclooxygenase-2 (COX-2) Revealed an Intronic Variant rs201231411 in Iranian Patients with Pancreatic Cancer

BACKGROUND There are hoarding documents for the biological importance of cyclooxygenase-2 (COX-2) in pancreatic carcinogenesis. We aimed to thoroughly investigate the DNA sequence variations of whole COX-2 exons in a large case-control study of pancreatic cancer by direct sequencing. METHODS The entire exonic regions of COX-2 including 10 exons were sequenced in the germline DNA of 96 patients with pancreatic cancer. Selected variants within exons six to seven (E6E7) amplicon from the test panel were genotyped in 96 controls. RESULTS The COX-2 gene was demonstrated to be genetically conserved. Four missense mutations were found in three cases. However the common variant c.724-10_724-7delATTT (rs201231411) that is located in intron 6, showed significant difference between cases and controls (21 [21.9%] vs 11 [%11.5], p=0.05). CONCLUSION This study determined that COX-2 has a conservative sequence, which is required for its enzymatic activity and supports the important role of this enzyme’s expression in pancreatic cancer rather than any changes in its activity. The effect of intronic variant rs201231411 on COX-2 expression could be analyzed in future studies.