Single nucleotide variants associated with colorectal cancer among Saudi patients: A systematic review.

Abstract

<h4>Objective</h4>To assess the variations in Single Nucleotide Polymorphisms (SNPs) that affect susceptibility of CRC in Saudi patients.<h4>Methods</h4>A systematic literature review was conducted following PRISMA guidelines. Electronic databases were searched from inception up to March 2025 using MeSH terms and keywords related to SNPs, Colorectal Cancer (CRC), and Saudi Arabia. Eligibility criteria mandated studies conducted on Saudi populations, including confirmed CRC cases and healthy controls (≥18 years), investigating SNP-CRC associations, and reporting risk estimates. Data on study characteristics, gene/SNP details, participant numbers, genotyping methods, risk estimates, p-values, and pathway categorization were extracted by two independent reviewers. The Newcastle-Ottawa Scale was used to assess the risk of bias in included case-control studies.<h4>Results</h4>Twenty-three case-control studies met the inclusion criteria, encompassing 2521 CRC cases and 2236 healthy controls. These studies investigated SNPs within 46 different genes. Significant associations (p < 0.05) with CRC risk were identified across various biological pathways. SNPs in inflammation/immune response genes (e.g., TNF-α, IL-17A, PD-1, CTLA-4, IL-10, TGFβ1) showed both increased and decreased risk associations. Variations in DNA repair (PARP-1, XRCC1, TP53) and cellular protection/drug metabolism genes (ABCC1, MDR1, GSTM1) also modulated susceptibility. Furthermore, SNPs in signaling pathways (VDR, MMP-2, NOTCH) and membrane/RNA-related genes (HER1, HER2, RETN, PRNCR1, HOTAIR) were significantly associated with CRC risk. Some allele frequencies (CYP19A) appeared distinct in the Saudi population compared to others. Most studies (77 %) were assessed as having a low risk of bias, though hospital-based control recruitment was a common limitation.<h4>Conclusion</h4>This systematic review confirms that numerous SNPs are significantly associated with altered CRC susceptibility in the Saudi population. These findings highlight a complex genetic landscape and underscore the potential value of identified SNPs for developing population-specific CRC risk assessment tools and targeted screening programs in Saudi Arabia.