Mohamadkhani Ashraf, Akbari Mohammad Reza, Ghanbari Reza, Naderi Elnaz, Rezanejad-Asl Parisa, Pourshams Akram
1. Liver and Pancreatobiliary Diseases Research Institute, Digestive Diseases.
2. Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Middle East J Dig Dis. 2015 Jan;7(1):14-8.
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.
关于环氧化酶-2（COX-2）在胰腺癌发生中的生物学重要性，存在大量文献。我们旨在通过直接测序，在一项大型胰腺癌病例对照研究中全面调查COX-2全外显子的DNA序列变异。方法：对96例胰腺癌患者的生殖系DNA中包括10个外显子的COX-2整个外显子区域进行测序。在96名对照中对测试组中外显子6至7（E6E7）扩增子内选定的变异进行基因分型。结果：COX-2基因显示出遗传保守性。在3例病例中发现了4个错义突变。然而，位于内含子6中的常见变异c.724-10_724-7delATTT（rs201231411）在病例和对照之间存在显著差异（21 [21.9%] 对11 [11.5%]，p=0.05）。结论：本研究确定COX-2具有保守序列，这是其酶活性所必需的，并支持该酶的表达在胰腺癌中的重要作用，而非其活性的任何变化。内含子变异rs201231411对COX-2表达的影响可在未来研究中进行分析。
