Research Laboratory "Environment, Inflammation, Signaling and Pathologies" (LR18ES40), Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.
Department of Clinical Oncology, CHU Fattouma Bourguiba, Monastir, Tunisia.
Clin Exp Med. 2020 Aug;20(3):427-436. doi: 10.1007/s10238-020-00632-5. Epub 2020 May 5.
Clinical implications of single nucleotide polymorphisms (SNPs) in breast cancer have been explored to determine the impact of SNP in modulating the pathogenesis of breast cancer. This study aimed to evaluate the association between HER2 (rs2517956) and (IL-6) (rs1800795 and rs2069837) and clinicopathological characteristics in HER2-positive and HER2-negative breast cancer in Tunisian women. A retrospective cohort study included 273 patients. Genomic DNA was extracted from peripheral blood samples, and genotyping of selected SNP was performed by PCR-RFLP assays. Statistical analysis was then carried out to assess genotypic frequencies and genetic association in relation to breast cancer subtypes. SHEsis software was applied to IL-6 haplotypic structure analysis. The distribution of genotype frequencies of rs2517956, rs1800795 and rs2069837 showed no statistically difference between HER2-positive and HER2-negative breast cancer. HER2 (rs2517956) was associated with tumor size (p = 0.01) and age at diagnosis (p = 0.02) in HER2-negative breast cancers, but no significant association was observed in HER2-positive breast cancer. For IL-6 gene, none of the clinicopathological parameters were associated with rs1800795 and rs2069837 in both breast cancer subtypes (p > 0.05). SHEsis analysis revealed a high linkage disequilibrium between rs1800795 and rs2069837; differences in the distribution of IL-6 two loci haplotypes were statistically negative between HER2-positive and HER2-negative breast cancer (p = 0.20) which confirmed no association with HER2 overexpression. This study demonstrates that rs2517956 is associated with clinicopathological characteristics in HER2-negative breast cancer, which could have a differential prognostic role compared to HER2-positive breast cancer.
本研究旨在评估在突尼斯女性的 HER2 阳性和 HER2 阴性乳腺癌中，HER2（rs2517956）和（IL-6）（rs1800795 和 rs2069837）单核苷酸多态性（SNPs）与临床病理特征之间的关联。一项回顾性队列研究纳入了 273 例患者。从外周血样本中提取基因组 DNA，并通过 PCR-RFLP 分析进行所选 SNP 的基因分型。然后进行统计分析，以评估与乳腺癌亚型相关的基因型频率和遗传关联。应用 SHEsis 软件进行 IL-6 单倍型结构分析。rs2517956、rs1800795 和 rs2069837 的基因型频率分布在 HER2 阳性和 HER2 阴性乳腺癌之间无统计学差异。在 HER2 阴性乳腺癌中，HER2（rs2517956）与肿瘤大小（p=0.01）和诊断时年龄（p=0.02）相关，但在 HER2 阳性乳腺癌中未观察到显著相关性。对于 IL-6 基因，在两种乳腺癌亚型中，rs1800795 和 rs2069837 均与任何临床病理参数无关（p>0.05）。SHEsis 分析显示 rs1800795 和 rs2069837 之间存在高度连锁不平衡；在 HER2 阳性和 HER2 阴性乳腺癌之间，IL-6 两个位点单倍型的分布差异具有统计学意义（p=0.20），这证实与 HER2 过表达无关。本研究表明，rs2517956 与 HER2 阴性乳腺癌的临床病理特征相关，与 HER2 阳性乳腺癌相比，可能具有不同的预后作用。
