ArticleBMC medical genomics2025
Genotypic and haplotype analysis of SOCS3 gene polymorphisms (rs4969169, rs12953258, rs1061489) in association with clinicopathological factors in breast cancer.
Article in BMC medical genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBreast cancer (BC) is the most common malignancy diagnosed among women worldwide. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a critical role in regulating cellular differentiation, maturation, proliferation, and apoptosis across various cell types involved in cancer initiation and progression. The suppressor of cytokine signaling 3 (SOCS3) acts as a key negative regulator of the JAK/STAT pathway. Therefore, investigating the role of single nucleotide polymorphisms (SNPs) in the SOCS3 gene is essential to better understand their contribution to the pathogenesis of breast cancer.
methodsThis case-control study included 300 female patients with breast cancer and 300 healthy female volunteers as controls. Ethical approval was obtained from the Institutional Ethics Committee prior to the commencement of study and was in compliance with the Helsinki Declaration. Written informed consent was obtained from all participants. Three SOCS3 SNPs-rs4969169 (C > T), rs12953258 (C > A), and rs1061489 (G > A)-were genotyped using Polymerase chain reaction-Restriction fragment length Polymorphism and Amplification refractory mutation system-PCR methods. Genotypic distributions, allele frequencies, and haplotype associations were analyzed, with statistical significance set at p < 0.05.
resultsThe TT genotype and T allele of rs4969169 (C > T) conferred 4.29-fold and 2.16-fold increased risk, respectively, for breast cancer. Similarly, the CA genotype and A allele of rs12953258 (C > A) were associated with 1.95-fold and 2.02-fold increased risk, while the GA genotype and A allele of rs1061489 (G > A) conferred 4.58-fold and 3.87-fold increased risk, respectively. Haplotype analysis revealed significant associations with advanced disease stage, lymph node involvement, lobular carcinoma, and negative receptor status for ER, PR, and HER2/neu. The T-C-G, C-A-G, C-C-A, and T-C-A haplotypes conferred 2.18-, 2.64-, 3.65-, and 13.66-fold increased risk, respectively, for breast cancer development.
conclusionTherefore, our study results suggest the significance of genotypic and haplotype analysis of SOCS3 gene polymorphisms and its impact on progression and risk prediction of breast cancer.
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