RESUMO
BACKGROUND: Functional variants -173 G > C (rs755622) and -794CATT5-8 (rs5844572) MIF gene have been associated with the risk in several types of cancer, as well as with the increase of soluble levels of MIF and TNFα. However, in previous studies contradictory and uncertain results have been presented on the implication of MIF polymorphisms with the association in cancer, specifically in breast cancer (BC). We investigated whether the variants are associated with the susceptibility to develop BC and the soluble levels of MIF and TNFα in women with BC from western Mexico. MATERIALS AND METHODS: A total of 152 women with BC and 182 control subjects (CS) were enrolled in this study. The determination of genotypes -173 G > C and -794 CATT5-8 MIF polymorphisms was performed by PCR-RFLP and PCR, respectively. In addition, the soluble levels of MIF and TNFα in both studied groups were quantified by ELISA and MILLIPLEX assay, respectively. RESULTS: The most frequent allele found in BC was the G (74.3%) and 6 (54%) in the variants -173G > C and -794 CATT5-8 , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT7 have higher levels of MIF in comparison with CS. An increase of MIF (BC: 11.1 ng/mL vs CS: 5.2 ng/mL, P < .001) and TNFα (BC: 24.9 ng/mL vs CS: 9.9 pg/mL, P < .001) was found. CONCLUSION: The functional variants of MIF are not genetic susceptibility markers for BC. Nevertheless, the alleles -173*C and -794CATT7 are associated with the increase of MIF circulating in women with BC.
Assuntos
Neoplasias da Mama/genética , Oxirredutases Intramoleculares/sangue , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores Inibidores da Migração de Macrófagos/genética , Fator de Necrose Tumoral alfa/sangue , Adulto , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , México , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Solubilidade , Fator de Necrose Tumoral alfa/genéticaRESUMO
Breast cancer (BC) is a health problem worldwide; there is evidence that inflammatory cytokines are increased in BC. Macrophage migration inhibitory factor (MIF) has multiple effects on immune cells, inflammation and cancer. Besides, in previous studies, contradictory and uncertain results have been presented on the implication of Th17 cytokine profile in BC. The aim of this study was to evaluate the plasma levels of MIF and the Th17 cytokine profile in BC and their association with their molecular subtypes and clinical stage. A total of 150 women with BC of Ella Binational Breast Cancer Study and 60 healthy women (HW) were evaluated in cross-sectional study. The molecular subtypes were identified by immunohistochemistry. The plasma levels of MIF were quantified by ELISA and Th17 cytokine profile by multiplex system. MIF and IL-17 were significantly increased in BC versus HW (11.1 vs. 5.2 ng/mL and 14.8 pg/mL vs. 2.5 pg/mL p < 0.001, respectively). Our analysis showed that both MIF and IL-17A were associated with increased risk of breast cancer (OR 3.85 CI 95% 1.98-7.50 and OR 4.51 95% 1.83-11.15, respectively), higher in aggressive subtypes Luminal B, HER2 and TN. Likewise, we observed positive correlation between MIF and IL-17A (p < 0.001). In addition, IL-17E was lower in BC versus HW (p <0.001). Likewise, we observed a positive correlation between MIF and IL-17A (p < 0.001). In conclusion, both MIF and IL-17A were associated with high risk for breast cancer and aggressive molecular subtypes.