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.

中文翻译：

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HER2和IL-6基因多态性与乳腺癌的临床病理特征之间的关联：遗传变异在特定乳腺癌亚型中的重要作用。

已经研究了单核苷酸多态性（SNP）在乳腺癌中的临床意义，以确定SNP在调节乳腺癌发病机理中的作用。这项研究旨在评估突尼斯妇女的HER2阳性和HER2阴性乳腺癌中HER2（rs2517956）和（IL-6）（rs1800795和rs2069837）与临床病理特征之间的关联。一项回顾性队列研究包括273名患者。从外周血样本中提取基因组DNA，并通过PCR-RFLP分析对所选SNP进行基因分型。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。将SHEsis软件应用于IL-6单倍型结构分析。rs2517956的基因型频率分布 rs1800795和rs2069837在HER2阳性和HER2阴性乳腺癌之间无统计学差异。HER2（rs2517956）与肿瘤大小有关（p  = 0.01）和HER2阴性乳腺癌的诊断年龄（p  = 0.02），但在HER2阳性乳腺癌中未观察到显着相关性。对于IL-6基因，在两种乳腺癌亚型中，没有任何临床病理参数与rs1800795和rs2069837相关（p  > 0.05）。SHEsis分析显示rs1800795和rs2069837之间存在高度连锁不平衡。HER2阳性和HER2阴性的乳腺癌之间IL-6两个基因座单倍型分布的差异在统计学上为阴性（p = 0.20）证实与HER2过表达无关。这项研究表明，rs2517956与HER2阴性乳腺癌的临床病理特征有关，与HER2阳性乳腺癌相比，其可能具有不同的预后作用。