Nouh Walaa E, El Azab Eman Fawzy, Oraby Enas A, Ahmed Shaymaa M, El-Eshmawy Mohamed Adel, Badawy Heba K, Shaaban Esraa Ibrahim A, El-Beltagy Nanis S, Alrub Heba Abu, Wahsh Eman, Elmashad Hanan Awad M, Elsaid Afaf M, Elhassan A-Elgadir Thoraya Mohamed, Toraih Eman, Elshazli Rami M, Alalawy Adel I, Attia Zeinab R
Mansoura University Children's Hospital, Mansoura University, Mansoura, Egypt.
Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Jouf University, Al Qurayyat, Saudi Arabia; Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
Gene. 2025 Mar 20;942:149259. doi: 10.1016/j.gene.2025.149259. Epub 2025 Jan 19.
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.
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.
The rs1801131C 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 rs1801133T 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 rs1042522G 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 rs1801131C/C genotype were associated with histological grade III, while those with the rs1801133T/T and rs1042522G/G genotypes were correlated with a moderate/poor NPI score (p-value < 0.05).
The rs1801131C, rs1801133T, and rs1042522G alleles are associated with an increased risk of BC. The rs1801133T 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.
已对亚甲基四氢叶酸还原酶（MTHFR）和抑癌基因（TP53）基因变异对乳腺癌（BC）易感性的影响进行了研究，但其结果尚无定论。本研究旨在采用遗传学和生物信息学方法，探讨MTHFR（rs1801131、rs1801133）和TP53（rs1042522）基因变异在BC风险增加中的潜在作用。
本研究共纳入242名女性参与者[142例BC患者和100名健康对照]。我们使用T-ARMS-PCR技术对这些基因变异进行等位基因鉴别分析。进行了逻辑回归、单倍型分析、遗传关联模型和多变量聚类分析。
与健康对照相比，在等位基因（OR = 2.02，p值<0.001）和隐性（OR = 3.26，p值<0.001）模型下，rs1801131C等位基因与乳腺癌风险升高显著相关。此外，在等位基因（OR = 1.81，p值 = 0.002）和显性（OR = 3.33，p值<0.001）模型下，rs1801133T等位基因与癌症易感性相关，而在等位基因（OR = 2.98，p值<0.001）和隐性（OR = 3.21，p值<0.001）模型下，rs1042522G等位基因与BC风险增加相关。携带rs1801131C/C基因型的BC女性与组织学III级相关，而携带rs1801133T/T和rs1042522G/G基因型的女性与中等/较差的NPI评分相关（p值<0.05）。
rs1801131C、rs1801133T和rs1042522G等位基因与BC风险增加相关。rs1801133T和rs1042522*G等位基因与中等/较差的NPI评分相关。这些发现为这些基因变异作为潜在预后生物标志物的诊断功能铺平了道路。
