Genetic variants and breast carcinoma susceptibility: Unveiling the role of MTHFR (rs1801131, rs1801133) and TP53 (rs1042522)

Background: The contribution of MTHFR and TP53 genetic variants to breast carcinoma (BC) susceptibility has been examined, but their findings have been inconclusive. This work is designed to explore the potential roles of the MTHFR (rs1801131, rs1801133) and TP53 (rs1042522) variants with increased risk of BC using genetic and bioinformatic approaches. Methods: This work included a total of 242 female participants [142 BCE patients and 100 healthy controls]. We genotyped the allelic discrimination analysis for these genetic variants using the T-ARMS-PCR technique. Logistic regression, haplotype analysis, genetic association models, and multivariate clustering were executed. Results: The rs1801131*C allele revealed a significant association with elevated risk of breast carcinoma compared to healthy controls under allelic (OR = 2.02, p-value < 0.001) and recessive (OR = 3.26, p-value < 0.001) models. Moreover, the rs1801133*T allele was correlated to cancer susceptibility under allelic (OR = 1.81, p-value = 0.002) and dominant (OR = 3.33, p-value < 0.001) models, while the rs1042522*G allele was associated with increased risk of BC under allelic (OR = 2.98, p-value < 0.001) and recessive (OR = 3.21, p-value < 0.001) models. BC women carrying the rs1801131*C/C genotype were associated with histological grade III, while those with the rs1801133*T/T and rs1042522*G/G genotypes were correlated with a moderate/poor NPI score (p-value < 0.05). Conclusions: The rs1801131*C, rs1801133*T, and rs1042522*G alleles are associated with an increased risk of BC. The rs1801133*T and rs1042522*G alleles correlated with moderate/poor NPI score. These findings pave the way for the diagnostic functions of these genetic variants as potential prognostic biomarkers.