Faculty of Sciences, El Manar University, Tunis, Tunisia; Nazarbayev University School of Medicine, Astana, Kazakhstan.
Faculty of Sciences, El Manar University, Tunis, Tunisia.
Clin Breast Cancer. 2023 Apr;23(3):272-280. doi: 10.1016/j.clbc.2022.12.017. Epub 2022 Dec 30.
Several studies documented that insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP2) contributes to carcinogenesis, and 1 report documented the association of IGF2BP2 rs4402960 with increased risk of breast cancer (BC). This study investigated the association of rs4402960 and rs1470579 IGF2BP2 variants with BC and triple negative BC (TNBC).
This case-control study included 488 BC patients comprising 130 TNBC and 358 non-TNBC patients, and 476 cancer-free controls. Genomic DNA was obtained from peripheral venous blood, and genotyping was done by allelic exclusion method on real-time PCR.
The rs440960, but not rs1470579, minor allele was significantly associated with BC, and significantly higher rs4402960 T/T genotype frequency was noted in BC patients than controls; the distribution of rs1470579 genotypes were comparable between BC patients and controls. In contrast, significantly lower rs1470579 minor allele frequency, and reduced rs1470579 A/C and C/C, and rs4402960 T/T genotype frequencies were seen in TNBC cases. Among TNBC cases, rs4402960 and rs1470579 correlated with menses pattern, histological type, breastfeeding, oral contraceptive use and hormonotherapy. Among non-TNBC patients, and rs1470579 correlated significantly with breast feeding, oral contraceptive use, hormonotherapy, and nodal status; rs4402960 also correlated with menses pattern. Two-locus (rs440960-rs1470579) haplotype analysis confirmed the positive association of TC, and negative association of GC and TA haplotypes with BC, while TC and GC haplotypes were negatively associated with TNBC.
Whereas rs440960 was positively associated with BC, both rs4402960 and rs1470579 were negatively associated with TNBC, suggesting potential diagnostic/prognostic role in BC and its complications.
几项研究表明胰岛素样生长因子-2 mRNA 结合蛋白 2（IGF2BP2）有助于癌症的发生，有一项研究报告表明 IGF2BP2 rs4402960 与乳腺癌（BC）风险增加有关。本研究调查了 rs4402960 和 rs1470579 IGF2BP2 变体与 BC 和三阴性 BC（TNBC）的关联。
本病例对照研究包括 488 名 BC 患者，其中 130 名 TNBC 和 358 名非 TNBC 患者，以及 476 名无癌对照。从外周静脉血中提取基因组 DNA，并通过实时 PCR 等位基因排除法进行基因分型。
rs440960 但不是 rs1470579 次要等位基因与 BC 显著相关，BC 患者的 rs4402960 T/T 基因型频率明显高于对照组；BC 患者与对照组的 rs1470579 基因型分布无差异。相反，TNBC 病例中 rs1470579 次要等位基因频率显著降低，rs1470579 A/C 和 C/C 以及 rs4402960 T/T 基因型频率降低。在 TNBC 病例中，rs4402960 和 rs1470579 与月经模式、组织学类型、母乳喂养、口服避孕药使用和激素治疗相关。在非 TNBC 患者中，rs1470579 与母乳喂养、口服避孕药使用、激素治疗和淋巴结状态显著相关；rs4402960 也与月经模式相关。双基因座（rs440960-rs1470579）单体型分析证实 TC 与 BC 呈正相关，GC 和 TA 单体型与 BC 呈负相关，而 TC 和 GC 单体型与 TNBC 呈负相关。
rs440960 与 BC 呈正相关，rs4402960 和 rs1470579 与 TNBC 呈负相关，提示其在 BC 及其并发症的诊断/预后中有潜在作用。
