Copyright ©The Author(s) 2021.
World J Gastroenterol. Jul 28, 2021; 27(28): 4653-4666
Published online Jul 28, 2021. doi: 10.3748/wjg.v27.i28.4653
Table 1 Summary of single nucleotide polymorphisms in whole region of cyclooxygenase-2 and their association with risk of cancer
SNP ID (rs number)Chromosome location (GRCh38)Cancer typeModelRegionEffectMAFOR (95%CI)P valueRef.
rs689465A>G1:186681714GastricG/APromoterSignificant interaction with H. pylori infection0.1430.84 (0.57-1.24)0.381Zhang et al[55]
rs689466G>A1:186681619GastricA/GPromoterIncreases transcriptional activity by creating a c-MYB binding site0.1761.19 (1.10-1.29)0.002aLi et al[14], Piranda et al[16], Zhang et al[55], Lopes et al[56], Liu et al[57], Shin et al[58], Guo et al[59], Zamudio et al[60], and Luo et al[61]
rs20417G>C1:186681189GastricC/GPromoterReduces promoter activity by creating a binding site for NPM and P-NPM0.1091.26 (1.12-1.41)< 0.001aLi et al[14], Piranda et al[16], Liu et al[17], Zhang et al[55], Shin et al[58], Sitarz et al[62], Saxena et al[63], Hou et al[64], Zhang et al[65], Campanholo et al[66], He et al[67], and Di Marco et al[68]
rs3218625G>A1:186674409GastricA/GPromoterEnhances activity of COX-2 in vitro by causing the transition of Gly to Aly < 0.0011.62 (1.02-2.56)0.039aZhang et al[55] and Zhang et al[65]
rs5277G>C1:186679065GastricGC/GGExon-0.1080.42 (0.13-1.28)0.127Hussain et al[69]
rs5278T>C1:186676537GastricTC/TTExon-0.0212.27 (0.53-9.69)0.270Hussain et al[69]
rs5279T>C1:186675946GastricTC/TTExon-0.0150.24 (0.08-0.73)0.012aHussain et al[69]
rs2745557G>A1:186680089PancreaticA/GIntron-0.1640.94 (0.64-1.39)0.764Özhan et al[70]
rs2066826G>A1:186676795PancreaticA/GIntron-0.1881.60 (1.06-2.40)0.026aÖzhan et al[70]
rs4648262G>T1:186679617PancreaticT/GIntron-< 0.0010.62 (0.22-1.73)0.364Özhan et al[70]
rs4648298A>G1:186672550ColorectalG/A3′-UTRCreates a longer and possibly more stable species of mRNA0.0210.44 (0.25-0.75)0.003aGholami et al[71], Mosallaei et al[72], and Cox et al[73]
rs5275T>C1:186673926GastricC/T3′-UTRStabilizes mRNA of COX-2 by potential miRNA-binding sites0.3511.14 (1.01-1.29)0.030aPiranda et al[16], Li et al[74], and Furuya et al[75]
rs689470T>C1:186671926GastricTC/TT3′-UTRDegradation of the mRNA0.0397.49 (1.21-46.20)0.030aHussain et al[69] and Hu et al[76]
rs2206593A>G1:186673297BreastG/A3′-UTR-0.0600.92 (0.84-1.91)0.088Li et al[77]
Table 2 Application of cyclooxygenase-2 inhibitors in cancer
DrugCancer typeEffect(s)MechanismRef.
CelecoxibGastricInhibits tumor growthIncreases CD206 and activates macrophagesThiel et al[46]
AspirinGastricInduces apoptosis; inhibits proliferation; inhibits angiogenesisAcetylates the active site of COX-2;inhibits PG synthesis; activates caspase-8/Bid and caspase-3Liu et al[57], and Niikura et al[78]
Oxadiazole 10cColonIncreases antitumor activity; increases sensitivityDocked into the COX-2 bind siteEl-Husseiny et al[79]
Celecoxib and platinumGastricProlong overall survival and progression-free survival-Guo et al[80]
Celecoxib and rapamycinGastricIncrease sensitivityInhibit PI3K/AKT pathwayCao et al[81]
Celecoxib and FOLFOX4GastricInhibit angiogenesisDown-regulate VEGF levelTołoczko-Iwaniuk et al[82]
Celecoxib and erlotinibColorectalReduce angiogenesis; inhibit formation; inhibit expansionInhibit EGFR signalingRoberts et al[83]
Celecoxib and CurcuminHepatocellularInhibit angiogenesis; inhibit proliferation; induce apoptosisInhibit Akt/NF-κB/PGE2/ROS pathway; inhibit COX-2/PGE2 pathwayAbdallah et al[84]
Sorafenib and meloxicamHepatocellularInhibit tumor cell growth; inhibit proliferation; enhance apoptosisActivate endoplasmic reticulum stress; enhance the cytotoxicityZhong et al[85]
Ferrocene derivativesBreast/cervicalSuppress tumor growth; increase antiproliferative activity; induce apoptosisIncrease the levels of cytotoxicity and reactive oxygen species; reduce the level of PGE2Ren et al[86], and Farzaneh et al[87]