Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, with 70% of cases attributed to sporadic mutations and the remaining linked to inherited genetic predispositions. This mini-review focuses on low-penetrance genetic variants that modestly influence CRC risk, categorizing them by mutation type - single nucleotide polymorphisms (SNPs) and non-SNP variants. Missense mutations in genes such as TP53, APC, CHEK2, and MUTYH are highlighted for their varying associations with CRC risk across populations. Additionally, silent mutations, untranslated region variants, and promoter modifications, such as those in PLA2G2A, XPA, and DNMT3B, are discussed for their potential, albeit modest, roles in CRC predisposition. Non-SNP variants, including deletions and insertions in genes like CHEK2, NOD2, GSTM1, and GSTT1, are explored for their frameshift effects and influence on CRC susceptibility. The review underscores the complexity of CRC risk, shaped by genetic, environmental, and lifestyle factors, and advocates for comprehensive, population-specific research to enhance genetic counseling and advance personalized medicine in CRC prevention and treatment.