Genetic Variants in RASSF1 (rs2073498), SERPINE1 (rs1799889), and EFNA1 (rs12904) Are Associated with Susceptibility in Mexican Patients with Colorectal Cancer: Clinical Associations and Their Analysis In Silico

<b>Background/Objectives:</b> Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Variants in genes that regulate processes such as apoptosis and angiogenesis play a significant role in CRC. The objective of this study is to investigate the possible association between <i>RASSF1</i> (rs2073498), <i>SERPINE1</i> (rs1799889), <i>EFNA1</i> (rs12904), and <i>RAD51</i> (rs1801320) variants and clinicopathological characteristics of Mexican patients with CRC. <b>Methods</b>: DNA of peripheral blood samples was obtained from 631 individuals (349 patients and 282 control individuals). The <i>RASSF1</i> (rs2073498), <i>SERPINE1</i> (rs1799889), <i>EFNA1</i> (rs12904), and <i>RAD51</i> (rs1801320) variants were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association was calculated using the odds ratio (OR) test. <i>p</i>-values were adjusted by the Bonferroni test (0.0125). In silico analysis programs, including Combined Annotation Dependent Depletion (CADD), Polymorphism Phenotyping-2 (PolyPhen-2), and Gene Expression Profiling Interactive Analysis (GEPIA), were conducted to predict the functional impact of these variants. <b>Results:</b> Patients carrying the G/A genotype of the <i>RASSF1</i> (rs2073498) variant showed an association with CRC characteristics, including TNM stages and tumor location (OR > 2.5, <i>p</i> = 0.001). Regarding the <i>SERPINE1</i> (rs1799889) variant, patients carrying the 5G/4G genotype showed an association between TNM stages and tumor location in the rectum (OR > 1.5, <i>p</i> ≤ 0.05). Patients with the G/G genotype for the <i>EFNA1</i> (rs12904) variant showed an association with TNM stages and rectal tumor location (OR > 2.0, <i>p</i> = 0.001). The <i>RAD51</i> (rs1801320) variant had no association with colorectal cancer. <b>Conclusions</b>: <i>RASSF1</i> (rs2073498), <i>SERPINE1</i> (rs1799889), and <i>EFNA1</i> (rs12904) variants significantly influence colorectal cancer risk.