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

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-01-19 DOI:10.1016/j.gene.2025.149259

Walaa E Nouh, Eman Fawzy El Azab, Enas A Oraby, Shaymaa M Ahmed, Mohamed Adel El-Eshmawy, Heba K Badawy, Esraa Ibrahim A Shaaban, Nanis S El-Beltagy, Heba Abu Alrub, Eman Wahsh, Hanan Awad M Elmashad, Afaf M Elsaid, Thoraya Mohamed Elhassan A-Elgadir, Eman Toraih, Rami M Elshazli, Adel I Alalawy, Zeinab R Attia

{"title":"Genetic variants and breast carcinoma susceptibility: Unveiling the role of MTHFR (rs1801131, rs1801133) and TP53 (rs1042522).","authors":"Walaa E Nouh, Eman Fawzy El Azab, Enas A Oraby, Shaymaa M Ahmed, Mohamed Adel El-Eshmawy, Heba K Badawy, Esraa Ibrahim A Shaaban, Nanis S El-Beltagy, Heba Abu Alrub, Eman Wahsh, Hanan Awad M Elmashad, Afaf M Elsaid, Thoraya Mohamed Elhassan A-Elgadir, Eman Toraih, Rami M Elshazli, Adel I Alalawy, Zeinab R Attia","doi":"10.1016/j.gene.2025.149259","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":12499,"journal":{"name":"Gene","volume":" ","pages":"149259"},"PeriodicalIF":2.6000,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.gene.2025.149259","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

遗传变异与乳腺癌易感性：揭示MTHFR （rs1801131, rs1801133）和TP53 （rs1042522）的作用。

背景：MTHFR和TP53基因变异对乳腺癌（BC）易感性的贡献已经被研究过，但他们的发现尚无定论。本研究旨在利用遗传和生物信息学方法探讨MTHFR （rs1801131, rs1801133）和TP53 （rs1042522）变异在增加BC风险中的潜在作用。方法：本研究共纳入242名女性受试者[142名BCE患者和100名健康对照]。我们使用T-ARMS-PCR技术对这些遗传变异进行等位基因分型分析。进行了逻辑回归、单倍型分析、遗传关联模型和多变量聚类。结果：rs1801131*C等位基因与乳腺癌风险升高相关（OR = 2.02， p值 ）。结论：rs1801131*C、rs1801133*T、rs1042522*G等位基因与BC风险升高相关。rs1801133*T和rs1042522*G等位基因与中/差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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.