Cyclooxygenase polymorphisms in gastric and colorectal carcinogenesis: are conclusive results available?

Objective Cyclooxygenases (COX) are important enzymes not only in the maintenance of mucosal integrity but also in pathological processes, namely in inflammation and tumor development in the gastrointestinal tract. Our goal was to understand whether there is a clear role for COX polymorphisms in gastric and colorectal carcinogenesis. Methods A systematic review was conducted on observational studies assessing the involvement of COX polymorphisms at the onset of gastric or colorectal lesions, retrieved through a MEDLINE database search by May 2008. The dominant genetic model was assumed for each polymorphism and a random-effect model was used for pooling results. Results Twenty-two studies were retrieved reporting a total of 26 COX polymorphisms (nine in COX1 and 17 in COX2 genes). Carriers of - 1329A, - 899C alleles, and *429TT genotype revealed increased risk for gastric cancer [odds ratio (OR) = 1.83; 95% confidence interval (Cl): 1.07-3.10, OR = 2.02; 95% Cl: 1.00-4.10 and OR = 1.34; 95% Cl: 1.06-1.71, respectively). For colorectal lesions, the - 899G > C and - 1329G >A polymorphisms also showed an increased risk for cancer (OR = 1.35; 95% Cl: 1.01-1.81 and OR = 1.36; 95% Cl: 1.11-1.66, respectively), Furthermore, C allele carriers of V102V single nucleotide polymorphisms presented a decreased risk for colorectal adenoma onset (OR=0.77; 95% Cl: 0.58-1.03). Conclusion Although further studies, namely cohorts and/or adequately matched case-control studies, are required to unravel the impact of most COX polymorphisms, clearly there are evidences that support the involvement of - 899G > C and - 1329G > A COX2 polymorphisms in either gastric or colorectal carcinogenesis. These markers could be used to optimize management strategies (follow-up and/or chemoprevention). Eur J Gastroenterol Hepatol 21:76-91 (C) 2009 Wolters Kluwer Health I Lippincott Williams & Wilkins.