Objective: To assess variations in Single Nucleotide Polymorphisms (SNPs) affecting colorectal cancer (CRC) susceptibility in Saudi patients.
Methods: A systematic literature review was conducted per PRISMA guidelines. Electronic databases were searched up to March 2025 using MeSH terms and keywords related to SNPs, CRC, and Saudi Arabia. Eligible studies included Saudi populations with confirmed CRC cases and healthy controls (≥18 years), investigating SNP-CRC associations with reported risk estimates. Data were extracted on study characteristics, SNP details, genotyping methods, and risk estimates. Risk of bias was assessed using the Newcastle-Ottawa Scale.
Results: Twenty-three case-control studies involving 2,521 CRC cases and 2,236 controls met inclusion criteria, covering 46 genes. Significant SNP-CRC associations (p < 0.05) were found across multiple biological pathways. SNPs in inflammation and immune response genes (e.g., TNF-α, IL-17A, PD-1, CTLA-4, IL-10, TGFβ1) showed both increased and decreased risk. Variants in DNA repair (PARP-1, XRCC1, TP53), drug metabolism (ABCC1, MDR1, GSTM1), signaling (VDR, MMP-2, NOTCH), and membrane/RNA-related genes (HER1, HER2, RETN, PRNCR1, HOTAIR) were also significantly associated. Distinct allele frequencies (e.g., CYP19A) were observed in the Saudi population. Most studies (77%) had low risk of bias, though hospital-based controls were a common limitation.
Conclusion: Numerous SNPs are significantly associated with CRC susceptibility in the Saudi population. These findings highlight a complex genetic landscape and suggest the potential for population-specific CRC risk assessment and targeted screening strategies in Saudi Arabia.
Keywords: Single Nucleotide Polymorphism, Saudi Arabia, Colorectal cancer, Genes, Genetic variation.