Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility

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 type	Model	Region	Effect	MAF	OR (95%CI)	P value	Ref.
rs689465A>G	1:186681714	Gastric	G/A	Promoter	Significant interaction with H. pylori infection	0.143	0.84 (0.57-1.24)	0.381	Zhang et al[55]
rs689466G>A	1:186681619	Gastric	A/G	Promoter	Increases transcriptional activity by creating a c-MYB binding site	0.176	1.19 (1.10-1.29)	0.002a	Li 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>C	1:186681189	Gastric	C/G	Promoter	Reduces promoter activity by creating a binding site for NPM and P-NPM	0.109	1.26 (1.12-1.41)	< 0.001a	Li 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>A	1:186674409	Gastric	A/G	Promoter	Enhances activity of COX-2 in vitro by causing the transition of Gly to Aly	< 0.001	1.62 (1.02-2.56)	0.039a	Zhang et al[55] and Zhang et al[65]
rs5277G>C	1:186679065	Gastric	GC/GG	Exon	-	0.108	0.42 (0.13-1.28)	0.127	Hussain et al[69]
rs5278T>C	1:186676537	Gastric	TC/TT	Exon	-	0.021	2.27 (0.53-9.69)	0.270	Hussain et al[69]
rs5279T>C	1:186675946	Gastric	TC/TT	Exon	-	0.015	0.24 (0.08-0.73)	0.012a	Hussain et al[69]
rs2745557G>A	1:186680089	Pancreatic	A/G	Intron	-	0.164	0.94 (0.64-1.39)	0.764	Özhan et al[70]
rs2066826G>A	1:186676795	Pancreatic	A/G	Intron	-	0.188	1.60 (1.06-2.40)	0.026a	Özhan et al[70]
rs4648262G>T	1:186679617	Pancreatic	T/G	Intron	-	< 0.001	0.62 (0.22-1.73)	0.364	Özhan et al[70]
rs4648298A>G	1:186672550	Colorectal	G/A	3′-UTR	Creates a longer and possibly more stable species of mRNA	0.021	0.44 (0.25-0.75)	0.003a	Gholami et al[71], Mosallaei et al[72], and Cox et al[73]
rs5275T>C	1:186673926	Gastric	C/T	3′-UTR	Stabilizes mRNA of COX-2 by potential miRNA-binding sites	0.351	1.14 (1.01-1.29)	0.030a	Piranda et al[16], Li et al[74], and Furuya et al[75]
rs689470T>C	1:186671926	Gastric	TC/TT	3′-UTR	Degradation of the mRNA	0.039	7.49 (1.21-46.20)	0.030a	Hussain et al[69] and Hu et al[76]
rs2206593A>G	1:186673297	Breast	G/A	3′-UTR	-	0.060	0.92 (0.84-1.91)	0.088	Li et al[77]

^aP < 0.05. SNP: Single nucleotide polymorphism; NPM: Nuceophosmin; P-NPM: Phosphorylated NPM; OR: Odds ratio; CI: Confidence interval; COX-2: Cyclooxygenase-2.

Table 2 Application of cyclooxygenase-2 inhibitors in cancer

Drug	Cancer type	Effect(s)	Mechanism	Ref.
Celecoxib	Gastric	Inhibits tumor growth	Increases CD206 and activates macrophages	Thiel et al[46]
Aspirin	Gastric	Induces apoptosis; inhibits proliferation; inhibits angiogenesis	Acetylates the active site of COX-2;inhibits PG synthesis; activates caspase-8/Bid and caspase-3	Liu et al[57], and Niikura et al[78]
Oxadiazole 10c	Colon	Increases antitumor activity; increases sensitivity	Docked into the COX-2 bind site	El-Husseiny et al[79]
Celecoxib and platinum	Gastric	Prolong overall survival and progression-free survival	-	Guo et al[80]
Celecoxib and rapamycin	Gastric	Increase sensitivity	Inhibit PI3K/AKT pathway	Cao et al[81]
Celecoxib and FOLFOX4	Gastric	Inhibit angiogenesis	Down-regulate VEGF level	Tołoczko-Iwaniuk et al[82]
Celecoxib and erlotinib	Colorectal	Reduce angiogenesis; inhibit formation; inhibit expansion	Inhibit EGFR signaling	Roberts et al[83]
Celecoxib and Curcumin	Hepatocellular	Inhibit angiogenesis; inhibit proliferation; induce apoptosis	Inhibit Akt/NF-κB/PGE2/ROS pathway; inhibit COX-2/PGE2 pathway	Abdallah et al[84]
Sorafenib and meloxicam	Hepatocellular	Inhibit tumor cell growth; inhibit proliferation; enhance apoptosis	Activate endoplasmic reticulum stress; enhance the cytotoxicity	Zhong et al[85]
Ferrocene derivatives	Breast/cervical	Suppress tumor growth; increase antiproliferative activity; induce apoptosis	Increase the levels of cytotoxicity and reactive oxygen species; reduce the level of PGE2	Ren et al[86], and Farzaneh et al[87]

COX-2: Cyclooxygenase-2; PGs: Prostaglandins; PI3K: Phosphatidylinositol 3 kinase; Akt (PKB): Protein kinase B; VEGF: Vascular endothelial growth factor; PGE2: Prostaglandin E2; ROS (MDA): Reactive oxygen species measured as malondialdehyde.