Differential effects of NOD2 polymorphisms on colorectal cancer risk: a meta-analysis

Since Kurzawski et al. described an association between the 3020insC NOD2 single nucleotide polymorphism and the risk of colorectal cancer(CRC) in 2004, reports published in the past several years have controversial results regarding the relationship between the development of CRC and NOD2 gene polymorphisms. To clarify the potential role of NOD2 P286S, R702W, G908R, and 3020insC polymorphisms in CRC patients, we have undertaken a systematic review and meta-analysis of published articles. Studies reporting on NOD2 polymorphisms and CRC were searched in the PubMed, EMBASE, and the Science Citation Index from the inception of each database to May, 2009. The search strategy included the keywords CRC, colon cancer, rectal cancer, polymorphism, and NOD2/CARD15. Eight eligible case-control studies about Caucasians from four countries contributed data on 5,888 subjects (cases: 3,524; controls: 2,364). Compared to the wild genotype, the R702W, G908R, and 3020insC polymorphisms were associated with an increased risk of CRC (odds ratio (OR): 1.59, 1.98, 1.44; 95% confidence interval (CI): 1.09-2.32, 1.14-3.44, 1.13-1.84; P = 0.02, 0.01, 0.003). However, P268S polymorphism did not influence CRC risk (OR: 1.27; CI: 0.32-5.00; P = 0.73). These findings indicate that NOD2 R702W, G908R, and 3020insC polymorphisms contribute to CRC susceptibility in Caucasians. Meta-analysis of these polymorphisms in NOD2 gene will help determine their role in CRC carcinogenesis.