NOD2 Polymorphisms and Their Association with Colorectal Cancer Risk: An Updated Systematic Review and Meta-Analysis

Background: Nucleotide-binding oligomerization domain-containing protein 2, encoded by NOD2, can trigger chronic gut inflammation that leads to colorectal cancer (CRC). However, studies that have investigated the association of NOD2 polymorphisms and CRC susceptibility have produced inconsistent findings. To clarify this relationship, a meta-analysis was conducted to integrate data from previous studies to achieve a more precise evaluation of the risk association. Methods: PubMed, Scopus, and Web of Science databases were systematically searched to identify relevant studies on the association of NOD2 polymorphisms with CRC risk. Genetic risk association was quantitatively assessed under five genetic models: homozygous, heterozygous, dominant, recessive, and allele. Thirteen studies, comprising 5,013 cases and 4,463 controls, were included in this study. Four NOD2 polymorphisms were investigated in these studies, namely rs2066842, rs2066844, rs2066845, and rs2066847. Results: Of these, only rs2066845 and rs2066847 were found to be significantly associated with increased CRC risk (rs2066845, heterozygous OR = 1.544, 95% CI = 1.014-2.349, P = 0.043; dominant OR = 1.561, 95% CI = 1.035-2.354, P = 0.034; allele OR = 1.572, 95% CI = 1.040-2.375, P = 0.032; rs2066847, heterozygous OR = 1.321, 95% CI = 1.060-1.647, P = 0.013; dominant OR = 1.402, 95% CI = 1.147-1.713, P = 0.001; allele OR = 1.345, 95% CI = 1.088-1.663, P = 0.006). Conclusions: In conclusion, the NOD2 rs2066845 and rs2066847 polymorphisms are associated with an increased risk of CRC and may potentially serve as predisposition biomarkers for the cancer.