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

TL;DR

This study finds that two NOD2 gene variations are linked to a higher risk of colorectal cancer, suggesting they could help identify people at higher risk.

Contribution

The study identifies two specific NOD2 polymorphisms (rs2066845 and rs2066847) as significant risk factors for colorectal cancer through a meta-analysis.

Findings

NOD2 polymorphisms rs2066845 and rs2066847 are significantly associated with increased CRC risk.

The study synthesized data from 13 studies involving over 9,000 participants to assess genetic risk.

These polymorphisms may serve as potential biomarkers for CRC predisposition.

Abstract

The NOD2 protein plays a crucial role in regulating intestinal inflammation. The dysregulation of NOD2, often due to genetic variations (polymorphisms), has been implicated in chronic gut inflammation and, consequently, increased colorectal cancer (CRC) risk. However, prior research on the association between NOD2 polymorphisms and CRC susceptibility has yielded inconsistent results. This meta-analysis aimed to synthesize the existing evidence to provide a more robust assessment of this association. Our findings indicate that two specific NOD2 polymorphisms, rs2066845 and rs2066847, are significantly associated with an elevated risk of CRC. These insights may contribute to the identification of individuals predisposed to CRC, thereby facilitating early detection and potentially guiding personalized preventive strategies in clinical practice.

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.

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