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  • Title: COX-2 polymorphisms and colorectal cancer risk: a strategy for chemoprevention.
    Author: Pereira C, Pimentel-Nunes P, Brandão C, Moreira-Dias L, Medeiros R, Dinis-Ribeiro M.
    Journal: Eur J Gastroenterol Hepatol; 2010 May; 22(5):607-13. PubMed ID: 20075740.
    Abstract:
    OBJECTIVE: COX-2, the inducible isoenzyme, was found to be overexpressed in approximately 85% of colorectal adenocarcinomas, contributing to key steps in tumor development. COX-2 polymorphisms that might modify the levels of protein expression would be anticipated to have a substantial influence on disease phenotype. Therefore, we sought to understand the role of three COX-2 polymorphisms (-1195A>G, -765G>C, and 8473T>C) in colorectal cancer (CRC) onset. MATERIAL AND METHODS: We conducted a hospital-based case-control study involving 117 consecutively enrolled CRC patients and 256 healthy individuals without any clinical evidence of cancer. The COX-2 polymorphisms' genotypes were characterized by PCR-restriction fragment length polymorphism or real-time PCR techniques. RESULTS: The -1195A>G polymorphism was associated with a 1.73-fold increased predisposition to CRC onset. In a stratified analysis, men and ever-smokers carrying -1195G allele (AG+GG) had an increased risk for CRC development (odds ratio: 2.58; 95% confidence intraval: 1.29-5.15 and odds ratio: 10.3; 95% confidence intraval: 3.37-31.2, respectively). More interestingly, men ever-smokers carrying -1195G allele appeared to have a nine-fold increased risk for CRC onset (95% CI: 2.94-27.6). No difference in the genotype's distribution was noticed between cases and controls for the remaining two polymorphisms. CONCLUSION: The -1195A>G COX-2 polymorphism seems to modulate the genetic susceptibility for CRC onset, especially in men ever-smokers. This genetically based higher-risk group definition may help shift the balance between risk and benefits for the use of COX-2 inhibitors in chemoprevention that is currently hampered by the adverse gastrointestinal and cardiovascular side-effects.
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