Abstract
ObjectiveCyclooxygenase-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.MethodsAll 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).ResultsTen 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.ConclusionsThe 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.
Highlights
Colorectal cancer (CRC) is the second most commonly diagnosed cancer with over 1.2 million new cases and 608,700 deaths in 2008 [1,2]
Most individuals exposing to these known risk factors never develop CRC while many CRC cases develop among individuals without those known risk factors, suggesting that other factors such as genetic factors play an important role in the development of CRC
In subgroup analysis according to source of control, significant increased CRC risk was not detected in hospital-based studies and population-base studies
Summary
Colorectal cancer (CRC) is the second most commonly diagnosed cancer with over 1.2 million new cases and 608,700 deaths in 2008 [1,2]. The highest incidence rate of CRC is found in Australia, Europe, and North America [2]. The incidence rate of CRC is rapidly increasing in a number of countries within Eastern Asia, such as China [2]. Accumulating evidence shows that COX-2 may play a key role in tumorigenesis of a variety of human malignancies by stimulating cell proliferation, inhibiting apoptosis, stimulating angiogenesis, and mediating immune suppression [6,7,8,9]. Several potentially functional single-nucleotide polymorphisms (SNP), 2765G.C (reference SNP ID, rs20417), 21195G.A (rs689466), and 8473T.C (rs5275) in the COX-2 gene have been identified. It is biologically reasonable to hypothesize a potential relationship between the COX-2 gene polymorphisms and CRC risk
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