STAT3 gene polymorphisms and susceptibility to breast cancer in the Moroccan population

Background: Breast cancer is a complex disease due to its extremely complicated and varied etiology. It is found to be linked to improper transcription factor activation that interferes with normal breast development. Among these factors, signal transducer and activator of transcription (STAT) proteins play a crucial role in regulating gene expression and cell signaling. Specifically, STAT3, a member of the STAT family, has been found to be constitutively active in various cancer types, including breast cancer. Three STAT3 SNPs (rs744166, rs229152, and rs4796793) were widely investigated in association with cancer diseases in many populations, yet the findings were conflicting. This study seeks to evaluate the association risk of these three SNPs with breast cancer in Moroccan women. Materials and methods: This case–control study consisted of 200 breast cancer cases and 200 age- and sex-matched healthy controls. The extraction was carried out from whole blood by the salting-out method. Genotypes were defined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and sequence-specific primer–polymerase chain reaction (SSP–PCR) methods. Results: In the over-dominant model (GG–CC vs. GC), the rs4796793*GC genotype was linked to a higher risk of breast cancer among triple-negative cases. Additionally, a significant association has been revealed between HER2 and the mutant genotype of the two polymorphisms rs744166 and rs4796793. Moreover, the STAT3 rs744166*AG genotype was less common in cases with late-stage (grade III) disease. Conclusion: These findings suggest that STAT3 polymorphisms are associated with triple-negative breast cancer and HER2+ type; the top two lethal breast cancer in Moroccans.