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Colorectal cancer (CRC) is one of the leading causes of cancer deaths globally. We implemented a comprehensive literature review regarding CRC genetics studies to offer a perception into the genes associated with CRC recognized in Saudi patients. Definite genetic variants in ABCB1, ADIPOQ, CTNNB1, SFRP3, LRP6, CYP19A1, PARP-1, TDG genes exhibited significant protection against CRC development in Saudi population. Whereas, other gene mutations in ABCB1, ABCC1, CASR, IL-17F, NOTCH1, NOTCH4, PRNCR1, TDG, TLR2, TLR4, TLR-9, TSLP, TSLPR and TNF-α genes showed irrelevant correlation with CRC risk in Saudi Arabia. On the other hand, specific mutations in ABCC1, ADIPOQ, CYP1A1, KIR, IL-17A, MMP2, NOTCH3, PRNCR1, RETN, TDG, TLR2, BRAF, PARP-1, TLR4, TLR-9, TNF-α, TSLP and XRCC1 genes demonstrated a substantial augmented CRC risk development in Saudi patients. Furthermore, ATR, ATM, BMI1, CCAT1, Chk1, Chk2, COX-2, FoxM1, FSCN1, Ki67, MALAT1, miR-29, miR-34a, miR-92, miR-182-5, PANDAR, PIK3CA, TIGAR over-expression revealed a robust association with CRC in Saudi Arabia (KSA). Moreover, gene alterations in APC, EGFR, FBXW7, TP53, PTEN, K-ras genes were concomitant in CRC. As well as, lower expression of MLH1, MSH2, MSH6, PMS2, EPCAM and MUTYH genes were recognized in LS patients and future CRC Saudi patients. These gene mutations may be used as diagnostic and/or prognostic genetic markers in CRC Saudi patients and could offer a potential therapeutic target for CRC management. [ABSTRACT FROM AUTHOR]