Avaliação da associação do polimorfismo do gene igf1r (rs2016347) com resposta à quimioterapia neoadjuvante em mulheres com câncer de mama

Abstract

Breast cancer (BC) has been recognized as the most common type of cancer in women. Cancer incidence and mortality are increasing worldwide, partly due to aging, population growth, as well as changes in the distribution and prevalence of cancer risk factors, especially those associated with genetic factors. Insulin-like growth factor 1 (IGF-1) plays a crucial role in human cancer biology, being associated with breast tumor formation and resistance to therapy, making it a target for antitumor agents. The absence or decrease of IGF-1 receptor (IGF-1R) expression after chemotherapy treatment were associated with a better therapeutic response. In addition, IGF-1 gene coding members are known to harbor several unique nucleotide polymorphisms (SNPs), which is understood to be a gene change, represented by changing a single pair of nitrogen bases. We then sought to identify genetic variants that influenced the expression of IGF-1 in patients with (CM). The aim of this study was to evaluate the association between the polymorphism (rs2016347) of insulin-like growth factor 1 (IGF-1R) with the response to neoadjuvant chemotherapy (QTNA), verify its genotypic distribution and evaluate the correlation of this polymorphism with pathological and immunohistochemical findings in women with CM followed in the mastology service of Santa Casa de Sobral – Ceará. An observational and prospective study was carried out with 40 female patients, who used chemotherapy in a neoadjuvant form. The genotyping of polymorphisms was performed by polymerase chain reaction (PCR) in real-time specific alleline. Statistical analysis was performed using Fisher's exact test, adopting a 95% confidence interval. Statistical significance was set at P < 0.05. The genotypes found and their distributions were respectively GG= 11 (27.5%), GT= 20 (50%), TT= 9 (22.5%). The presence of the T allele was significantly associated with response to neoadjuvant chemotherapy, such as tumor size reduction (p=<0.023), better axillary lymph node status (p=<0.05), with no association with the markers immunohistochemicals evaluated such as hormone receptors (p=>0.23), HER2 (p=0.395) and KI67 (p=>0.43).