Genotype-phenotype correlations in breast cancer susceptibility: evaluating MMP-2, TYMS, and eNOS variants in the Jordanian population

Breast cancer (BC) is a complex, polygenic, and heterogeneous disease influenced by both genetic and environmental factors. Several genetic polymorphisms, including single nucleotide variants (SNVs) and variable number tandem repeats (VNTRs), have been implicated in BC susceptibility and prognosis across diverse populations. This study aimed to assess the association between genetic variants in the MMP-2, TYMS, and eNOS genes and breast cancer risk in the Jordanian population. A case-control study was conducted involving 300 BC patients and 321 healthy controls. Genotyping was performed using conventional PCR and PCR-RFLP techniques to analyze one SNV in MMP-2 (rs2285053) and two VNTRs in TYMS (rs45445694) and eNOS. The MMP-2 SNV (rs2285053) and TYMS VNTR (rs45445694) showed significant associations with increased BC risk, whereas the eNOS VNTR exhibited no significant correlation. Significant genetic associations were identified under the co-dominant and recessive models, particularly for the T/T and C/T genotypes compared with C/C. No significant relationship was found between these variants and patient survival; however, TYMS mRNA expression was significantly associated with survival probability (p = 0.0185). Overall, these findings suggest that MMP-2 and TYMS variants contribute to breast cancer susceptibility among Jordanians, with TYMS expression serving as a potential prognostic biomarker.