Association of the genetic variants (-794 CATT5-8 and -173 G > C) of macrophage migration inhibitory factor (MIF) with higher soluble levels of MIF and TNFα in women with breast cancer.

ABSTRACT

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.