Abstract
MicroRNA machinery genes Argonaute 1 (
AGO1
) and 2 (
AGO2
) are associated with several hallmarks of cancer. They play a key role in transcriptomic silencing, regulation of the immune system, cell differentiation, and angiogenesis processes. The present pilot study aims to explore the impact of genetic variants rs636832 and rs2977490 of
AGO1
and
AGO2
, respectively, on breast cancer (BC) risk in a sample of Mediterranean population. TaqMan genotyping assay of 93 consecutive breast cancer female patients and age- as well as ethnicity-matched controls, was done by Real-Time allele discrimination polymerase chain reaction. Association with the available clinical, histopathological and immunohistochemistry assessments was applied.
In silico
data analysis was also executed. Although allele and genotype frequencies distribution of both study variants were comparable in BC and healthy control cohorts,
AGO1*G
variant conferred a significant BC risk under recessive model [adjusted odds ratio (95% confidence interval); 4.90 (1.03-23.39),
P
= 0.024], and was significantly associated with lymph node infiltration (
P
= 0.037), distant metastasis (
P
= 0.019), advanced clinical stage (
P
< 0.001), recurrence (
P
= 0.032), and shorter overall survival (
P
= 0.001). Furthermore,
AGO2*G/G
genotype showed an association with poor pathological grade (
P
= 0.029). Our results suggested for the first time that rs636832 and rs2977490 variants of the miRNA-machinery genes
AGO1
and
2
, respectively, may impact susceptibility and/or clinical outcomes of BC patients in the study population.