Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies

Qiliu Peng; Shi Yang; Xianjun Lao; Weizhong Tang; Zhiping Chen; Hao Lai; Jian Wang; Jingzhe Sui; Xue Qin; Shan Li

doi:10.1371/journal.pone.0094790

Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies

PLoS One. 2014 Apr 14;9(4):e94790. doi: 10.1371/journal.pone.0094790. eCollection 2014.

Authors

Qiliu Peng¹, Shi Yang¹, Xianjun Lao¹, Weizhong Tang², Zhiping Chen³, Hao Lai⁴, Jian Wang¹, Jingzhe Sui¹, Xue Qin¹, Shan Li¹

Affiliations

¹ Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
² Department of Anal and Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
³ Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi, China.
⁴ Department of Gastrointestinal Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Colorectal Neoplasms / enzymology*
Colorectal Neoplasms / genetics*
Cyclooxygenase 2 / genetics*
Genetic Association Studies*
Genetic Heterogeneity
Genetic Predisposition to Disease*
Humans
Models, Genetic
Polymorphism, Single Nucleotide / genetics*
Publication Bias
Risk Factors

Substances

Cyclooxygenase 2
PTGS2 protein, human

Grants and funding

This research was supported by National Natural Science Foundation of China (No. 81260302). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.