miR 155 rs767649 T>A gene polymorphism is associated with downregulation of miR?155 expression, suppressor of cytokine signaling?1 overexpression, and low probability of metastatic tumor at the time of breast cancer diagnosis

Abstract

Background: MicroRNA?155 is a key player in inflammatory reactions, carcinogenesis, and tumor development. In this study, polymorphism of miRNA?155 rs767649 T>A and its gene and suppressor of cytokine  ignaling?1 (SOCS?1) expression were investigated in relation to cancer susceptibility and development in breast cancer (BC) patients.

Materials and Methods: Polymorphism of miRNA?155 rs767649 T>A was evaluated between a population of 174 patients with BC and 129 controls using restriction fragment length polymorphism and the expression of miR?155 and SOCS?1 were examined in peripheral blood mononuclear cells (PBMCs) by real?time polymerase chain reaction.

Results: TT genotype of miR?155 rs767649 T>A was associated with higher level of miR?155 in PBMCs of BC patients relative to AT and AA genotypes (21.76 ± 4.4, 4.046 ± 1.35, 2.56 ± 0.81, respectively; P < 0.001) and increased lymph node metastasis (r = 0.292, P = 0.001), not BC susceptibility (P = 0.402 and P = 0.535; respectively). TT genotype of miR?155 rs767649 T>A was associated with less gene expression of SOCS?1 in PBMCs of BC patients compared to AT and AA genotypes (1.173 ± 0.57, 0.92 ± 0.827, 5.512 ± 0.92, respectively; P = 0.003).

Conclusion: This study demonstrated for the first time the association between the T allele of the rs767649 T>A polymorphism in the pre?MIR155 gene and higher expression of miR?155, lower expression of SOCS?1, and swift latent progression in newly diagnosed BC patients. Thus, miR?155 may play a critical role in BC pathogenesis.