No evidence for association of NOD2 R702W and G908R with colorectal cancer

Polymorphisms in nucleotide oligomerization domain 2 gene (NOD2) have been associated with increased susceptibility to Crohn's disease. Recently, possible association of the NOD2 variants R702W, G908R and 3020insC with colorectal cancer (CRC) has been studied among Polish, Greek., Finnish and New Zealand Caucasian CRC patients, but the results have been controversial. In the Polish study, 3020insC alone, and in the Greek study all the 3 variants, showed association with CRC. In a study from New Zealand, R702W appeared to increase CRC risk. In addition, the combined frequencies of the 3 variants were significantly elevated in CRC patients compared with healthy controls. We have previously shown that NOD2 3020insC is not associated with increased CRC risk in Finland. In the current study, we have genotyped the R702W and G908R in a population -based series of 1,042 CRC patients and in 508 healthy controls to study the possible contribution of these variants to CRC predisposition. Of the CRC patients, 953 were successfully analyzed. R702W and G908R were equally, frequently seen in CRC patients and controls (R702W: 2.2% vs. 2.1%; G908R: 0.3% vs. 0.2%). No associations between NOD2 variants and clinical characteristics were observed. Our results indicate that NOD2 variants R702W, (G908R and 3020insC do not predispose to CRC in Finland. Environmental or additional genetic factors may play a role in CRC development in NOD2 variant carriers. Further work is necessary to establish the possible role of NOD2 variants in CRC predisposition. (C) 2007 Wiley-Liss, Inc.