Omran Moataza H, Fotouh Basma E, Shousha Wafaa G, Ismail Abeer, Ibrahim Noha E, Ramadan Shimaa S
Department of Microbial Biotechnology, Genetic Engineering Division, National Research Centre, Cairo, Egypt.
Department of Chemistry, Faculty of Science, Helwan University, Cairo, Egypt.
Asian Pac J Cancer Prev. 2021 Feb 1;22(2):617-626. doi: 10.31557/APJCP.2021.22.2.617.
Globally, Breast cancer (BC) is considered the second most common type of cancer and the principal cause of death among affected women.
In this study, we targeted to demonstrate the association of MTHFR single gene polymorphisms (SNPs) with the susceptibility of breast cancer, in addition to its correlation with the clinical patient features.
This work was conducted on 100 Egyptian females with breast cancer and 60 healthy matched controls. Clinical examinations and pathological investigations were recorded. Genotyping of MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) by using Restriction Fragment length Polymorphisms (RFLP) and Sequencing assays were performed. Univariate, Multivariate and Haplotype analysis for the allelic frequencies and the association with clinicopathological features of BC were assessed.
The present data showed a strong significant association between the CT and TT of MTHFR (C677T), and AC and CC of (A1289C) with the susceptibility of BC showing highly statistical P- value (0.001). It was also demonstrated that the most frequent haplotype of the two loci of MTHFR (rs1801133-rs1801131) was TC. The latter was strongly associated with the aggressive clinical features of each of tumor size, advanced stage, involvement of cancer in lymph nodes, overexpression of HER2neu and dual negativity of both ER and PR hormones.
SNPs within the MTHFR gene (C677T) and (A1289C) have strong correlation with BC among Egyptian females; These SNPs should be considered as important prognostic markers for identifying the individuals at high risk of developing BC and its progression.
在全球范围内，乳腺癌（BC）被认为是第二大常见癌症类型，也是受影响女性的主要死亡原因。
在本研究中，我们旨在证明亚甲基四氢叶酸还原酶（MTHFR）单基因多态性（SNP）与乳腺癌易感性的关联，以及其与临床患者特征的相关性。
这项研究针对100名患有乳腺癌的埃及女性和60名健康匹配对照进行。记录临床检查和病理调查结果。采用限制性片段长度多态性（RFLP）和测序分析对MTHFR基因多态性C677T（rs1801133）和A1298C（rs1801131）进行基因分型。评估等位基因频率的单因素、多因素和单倍型分析以及与乳腺癌临床病理特征的关联。
目前的数据显示，MTHFR（C677T）的CT和TT以及（A1289C）的AC和CC与乳腺癌易感性之间存在强烈的显著关联，具有高度统计学意义的P值（0.001）。还证明了MTHFR两个位点（rs1801133 - rs1801131）最常见的单倍型是TC。后者与肿瘤大小、晚期、癌症淋巴结受累、HER2neu过表达以及雌激素受体和孕激素受体双阴性等侵袭性临床特征密切相关。
MTHFR基因（C677T）和（A1289C）内的单核苷酸多态性与埃及女性的乳腺癌有很强的相关性；这些单核苷酸多态性应被视为识别患乳腺癌及其进展高风险个体的重要预后标志物。
