Due to the overwhelming burden of colorectal cancer (CRC), great effort has been placed on identifying genetic mutations that contribute to disease development and progression. One of the most studied polymorphisms that could potentially increase susceptibility to CRC involves the nucleotide-binding and oligomerization-domain containing 2 (NOD2) gene. There is growing evidence that the biological activity of NOD2 is far greater than previously thought and a link with intestinal microbiota and mucosal immunity is increasingly sought after. In fact, microbial composition may be an important contributor not only to inflammatory bowel diseases (IBD) but also to CRC. Recent studies have showed that deficient NOD2 function confers a communicable risk of colitis and CRC. Despite the evidence from experimental models, population-based studies that tried to link certain NOD2 polymorphisms and an increase in CRC risk have been described as conflicting. Significant geographic discrepancies in the frequency of such polymorphisms and different interpretations of the results may have limited the conclusions of those studies. Since being first associated to IBD and CRC, our understanding of the role of this gene has come a long way, and it is tempting to postulate that it may contribute to identify individuals with susceptible genetic background that may benefit from early CRC screening programs or in predicting response to current therapeutic tools. The aim of this review is to clarify the status quo of NOD2 mutations as genetic risk factors to chronic inflammation and ultimately to CRC. The use of NOD2 as a predictor of certain phenotypic characteristics of the disease will be analyzed as well.

• Colorectal cancer
• Fecal microbiota
• Cancer susceptibility
• Intestinal inflammation
• Nucleotide-binding and oligomerization-domain containing 2 mutations

• XRCC4
• age at diagnosis
• breast cancer
• polymorphism
• susceptibility

Purpose. Our study aimed to assess a possible correlation between NOD2 Arg702Trp (rs2066844) polymorphism and gastric cancer risk in a Romanian population. Material/Methods. A total of 322 subjects (72 patients with gastric adenocarcinoma and 250 healthy controls) were included. Genomic DNA was extracted from blood leukocytes and NOD2 Arg702Trp polymorphism was genotyped by Real-Time PCR using specific TaqMan probes. Results. No statistically significant difference was observed between gastric cancer patients and controls when we compared one genotype with other genotype (the CC genotype serves as reference) (OR 0.45, 95% CI: 0.10 - 2.05) or when we compared allele frequencies (the C allele serves as reference) (OR 0.46, 95% CI: 0.11 - 2.04). We examined separately the association of this polymorphism with tumor site and histologic type and no correlation was found. Conclusion. NOD2 Arg702Trp polymorphism is not associated with gastric cancer risk and further investigations are needed to elucidate the contribution of NOD2 gene in gastric carcinogenesis.

• NOD2 polymorphism
• gastric cancer
• gene
• genotype