Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
Department of Radiation Oncology, Cancer Research Center, Guilan University of Medical Sciences (GUMS), Rasht, Iran.
Breast Cancer Res Treat. 2023 Nov;202(2):389-395. doi: 10.1007/s10549-023-07070-3. Epub 2023 Aug 1.
This project aimed to evaluate the relationship between the suppressor of cytokine signaling-1 (SOCS1) - 1478 CA > del genetic variation and breast cancer susceptibility. Moreover, we investigated the SOCS1 mRNA expression level in cancerous tissues.
A total of 100 patients with breast cancer and 120 healthy individuals were selected. Genomic DNA was extracted from blood. SOCS1 genotyping and relative gene expression were performed using ARMS-PCR (Amplification-Refractory Mutation System-Polymerase Chain Reaction) and real-time PCR, respectively.
In breast cancer patients, the prevalence of genotype frequencies of SOCS1 (- 1478 CA > del) CA/CA, CA/del, and del/del was 52, 31, and 17%, respectively. Among controls, the distribution of CA/CA, CA/del, and del/del was 63, 15, and 22%, respectively. The chi-square test reported that a significant difference was observed in the genotypic distribution of SOCS1 (- 1478 CA > del) polymorphism between cases and controls (χ = 8.08, P = 0.01). In addition, the presence of the CA/del genotype was associated with an elevated risk of breast cancer (in the codominant model: OR 2.51; 95% CI 1.27-4.96, P = 0.007 and in the over dominant model: OR 2.54; 95% CI 1.32-4.90, P = 0.005). However, there was no significant difference in allelic distributions between the groups (P > 0.05). There was no significant difference in the breast cancer risk associated with the dominant and recessive genetic models when the reference was CA/CA and CA/CA + CA/del genotype, respectively (P = 0.09 and P = 0.38). Moreover, the expression of SOCS1 decreased in cancerous tissues as compared to the adjacent non-cancerous tissues (P < 0.0001).
In conclusion, a functional SOCS1 promoter polymorphism (- 1478 CA > del) may affect breast cancer susceptibility.
本项目旨在评估细胞因子信号转导抑制因子-1（SOCS1）-1478 CA > del 遗传变异与乳腺癌易感性之间的关系。此外，我们还研究了 SOCS1 mRNA 在癌组织中的表达水平。
选择了 100 名乳腺癌患者和 120 名健康个体。从血液中提取基因组 DNA。采用 ARMS-PCR（扩增阻遏突变系统-聚合酶链反应）和实时 PCR 分别进行 SOCS1 基因分型和相对基因表达。
在乳腺癌患者中，SOCS1（-1478 CA > del）CA/CA、CA/del 和 del/del 基因型频率的发生率分别为 52%、31%和 17%。在对照组中，CA/CA、CA/del 和 del/del 的分布分别为 63%、15%和 22%。卡方检验报告称，病例组和对照组 SOCS1（-1478 CA > del）多态性的基因型分布存在显著差异（χ²=8.08，P=0.01）。此外，CA/del 基因型的存在与乳腺癌的发生风险升高相关（在共显性模型中：OR 2.51；95%CI 1.27-4.96，P=0.007；在超显性模型中：OR 2.54；95%CI 1.32-4.90，P=0.005）。然而，两组间等位基因分布无显著性差异（P > 0.05）。当参考基因型为 CA/CA 和 CA/CA+CA/del 时，与显性和隐性遗传模型相关的乳腺癌风险无显著差异（P=0.09 和 P=0.38）。此外，与相邻非癌组织相比，癌组织中 SOCS1 的表达降低（P < 0.0001）。
总之，SOCS1 启动子功能多态性（-1478 CA > del）可能影响乳腺癌易感性。
