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

Area of Science:

• Genetics
• Oncology
• Gastroenterology

Background:

• Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is implicated in chronic gut inflammation, a precursor to colorectal cancer (CRC).
• Previous studies on the association between NOD2 polymorphisms and CRC susceptibility have yielded conflicting results.
• A meta-analysis was performed to consolidate existing data for a clearer understanding of this relationship.

Purpose of the Study:

• To clarify the association between NOD2 polymorphisms and colorectal cancer (CRC) risk.
• To provide a more precise evaluation of the genetic risk by integrating data from multiple studies.

Main Methods:

• A systematic literature search was conducted across PubMed, Scopus, and Web of Science.
• Included studies were analyzed quantitatively using five genetic models: homozygous, heterozygous, dominant, recessive, and allele.
• Data from 13 studies (5,013 cases, 4,463 controls) investigating four NOD2 polymorphisms (rs2066842, rs2066844, rs2066845, rs2066847) were synthesized.

Main Results:

• The NOD2 polymorphisms rs2066845 and rs2066847 showed a significant association with increased CRC risk.
• Specifically, rs2066845 demonstrated increased risk under heterozygous, dominant, and allele models (P values ranging from 0.043 to 0.032).
• Rs2066847 also indicated a significant association with elevated CRC risk across heterozygous, dominant, and allele models (P values ranging from 0.013 to 0.006).

Conclusions:

• The NOD2 gene polymorphisms rs2066845 and rs2066847 are associated with an elevated risk of developing colorectal cancer.
• These specific NOD2 polymorphisms may function as potential biomarkers for predicting CRC predisposition.