title: Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association.
  
  
  METHODS
  All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).
  
  
  RESULTS
  Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004). In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses.
  
  
  CONCLUSIONS
  The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer patients. Further large and well-designed studies are needed to confirm this association.
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Qiliu
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Lao
authors.affiliation: Department of Anal and Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Jingzhe
authors.initials: J
authors.lastname: Sui
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias; D012307:Risk Factors
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
references.citation: Clin Transl Sci. 2012 Feb;5(1):60-4
references.pmid: 22376259
references.citation: Eur J Hum Genet. 2013 Dec;21(12):1389-95
references.pmid: 23531863
references.citation: Br J Cancer. 2004 May 4;90(9):1760-4
references.pmid: 15150618
references.citation: Biometrics. 2000 Jun;56(2):455-63
references.pmid: 10877304
references.citation: BMC Cancer. 2009 Nov 21;9:407
references.pmid: 19930591
references.citation: J Natl Cancer Inst. 2012 Oct 3;104(19):1433-57
references.pmid: 23019048
references.citation: J Natl Cancer Inst. 1959 Apr;22(4):719-48
references.pmid: 13655060
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Stat Med. 2002 Jun 15;21(11):1539-58
references.pmid: 12111919
references.citation: Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1631-6
references.pmid: 12377741
references.citation: Mol Biol Rep. 2012 May;39(5):5219-24
references.pmid: 22173719
references.citation: Prostate. 2002 Nov 1;53(3):232-40
references.pmid: 12386924
references.citation: Cancer Causes Control. 2013 Dec;24(12):2059-75
references.pmid: 24022467
references.citation: Clin Cancer Res. 2005 Jun 1;11(11):4090-6
references.pmid: 15930344
references.citation: Int J Cancer. 2006 Jul 15;119(2):297-303
references.pmid: 16482563
references.citation: Int J Biochem Cell Biol. 1999 May;31(5):551-7
references.pmid: 10399316
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G7-17
references.pmid: 15194558
references.citation: Mol Cell Biochem. 2011 Jan;347(1-2):201-8
references.pmid: 21042835
references.citation: Fam Cancer. 2013 Dec;12(4):755-65
references.pmid: 23715757
references.citation: CA Cancer J Clin. 2012 Nov-Dec;62(6):364-93
references.pmid: 23070605
references.citation: Mol Biol Rep. 2011 Jun;38(5):3481-6
references.pmid: 21107726
references.citation: World J Gastroenterol. 2008 Mar 21;14(11):1785-9
references.pmid: 18350611
references.citation: Biochem Biophys Res Commun. 1994 Aug 30;203(1):190-9
references.pmid: 8074655
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Eur J Gastroenterol Hepatol. 2010 May;22(5):607-13
references.pmid: 20075740
references.citation: Recent Results Cancer Res. 2013;191:157-83
references.pmid: 22893205
references.citation: World J Gastroenterol. 2009 Sep 28;15(36):4561-5
references.pmid: 19777615
references.citation: Med Oncol. 2011 Dec;28(4):1436-40
references.pmid: 20645029
references.citation: BMJ. 1997 Sep 13;315(7109):629-34
references.pmid: 9310563
references.citation: J Gastroenterol Hepatol. 2010 Jun;25(6):1042-50
references.pmid: 20594217
references.citation: Clin Cancer Res. 2005 May 1;11(9):3250-6
references.pmid: 15867220
references.citation: Urology. 2001 Aug;58(2 Suppl 1):127-31
references.pmid: 11502467
references.citation: JAMA. 2000 Apr 19;283(15):2008-12
references.pmid: 10789670
references.citation: Tohoku J Exp Med. 2010 Sep;222(1):15-21
references.pmid: 20808059
references.citation: Asian Pac J Cancer Prev. 2001;2(1):57-62
references.pmid: 12718655
references.citation: J Allergy Clin Immunol. 2004 Aug;114(2):248-53
references.pmid: 15316498
references.citation: J Toxicol Environ Health A. 2007 Jun;70(11):908-15
references.pmid: 17479405
references.citation: Int J Cancer. 2012 Apr 15;130(8):1898-907
references.pmid: 21618522
references.citation: Cancer Causes Control. 2009 Oct;20(8):1421-9
references.pmid: 19468846
references.citation: Chem Rev. 2011 Oct 12;111(10):5899-921
references.pmid: 21923193
references.citation: Cancer Metastasis Rev. 2011 Dec;30(3-4):343-61
references.pmid: 22038018
references.citation: World J Gastroenterol. 2009 May 14;15(18):2240-4
references.pmid: 19437564
references.citation: Br J Cancer. 2004 Jul 19;91(2):339-43
references.pmid: 15173859
references.citation: Carcinogenesis. 2007 Jun;28(6):1197-201
references.pmid: 17151091
references.citation: J Viral Hepat. 2012 Sep;19(9):608-14
references.pmid: 22863264
references.citation: Tumour Biol. 2012 Aug;33(4):957-66
references.pmid: 22252523
references.citation: Clin Exp Metastasis. 2002;19(7):593-601
references.pmid: 12498388
references.citation: Carcinogenesis. 2004 Dec;25(12):2467-72
references.pmid: 15308583
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120