Dataset Information

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 TNF? 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 TNF?. 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 TNF? 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 TNF? 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 TNF? (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.

SUBMITTER: Avalos-Navarro G

PROVIDER: S-EPMC7246356 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Avalos-Navarro Guadalupe G Del Toro-Arreola Alicia A Daneri-Navarro Adrián A Quintero-Ramos Antonio A Bautista-Herrera Luis Alberto LA Franco Topete Ramon Antonio RA Anaya Macias Brian Uriel BU Javalera Castro David Israel DI Morán-Mendoza Andrés de Jesús AJ Oceguera-Villanueva Antonio A Topete-Camacho Antonio A Muñoz-Valle José Francisco JF

Journal of clinical laboratory analysis 20200124 5

<h4>Background</h4>Functional variants -173 G > C (rs755622) and -794CATT<sub>5-8</sub> (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 susceptibi ...[more]

PMID: 31978276

Similar Datasets

Project description:BackgroundMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and mediator of acute and chronic inflammatory diseases. MIF is overexpressed in various tumours and has been suggested as a molecular link between chronic inflammation and cancer. MIF overexpression is observed in breast cancer but its causal role in the development of this tumour entity is unclear.MethodsMIF levels in breast cancer cell lines were determined by ELISA and Western blot. CD74 was measured by Western blot, fluorescence microscopy and flow cytometry. Cell proliferation was studied by BrdU incorporation, cell adhesion by Matrigel adhesion assay, and cell invasion by migration assay through Matrigel-coated filters using the Transwell system. MIF expression in primary human breast cancers was measured by tissue microarray and a semi-quantitative immunoreactivity score (IRS) and comparison with histopathological parameters and patient outcome data.ResultsMIF was abundantly expressed in the non-invasive breast cancer cell lines MDA-MB-468 and ZR-75-1, but not in invasive MDA-MB-231 cells, which in turn expressed higher levels of the MIF-receptor CD74. Stimulation with exogenous MIF led to a dramatic upregulation of MIF secretion (50-fold) in MDA-MB-231 cells. Autocrine MIF promoted tumour cell proliferation, as indicated by blockade of MIF or CD74 in MDA-MB-231 and MDA-MB-468, and MDA-MB-231 invasiveness was enhanced by exogenous MIF. We correlated the expression of MIF with histopathological parameters and patient outcome data, using a tissue microarray of 175 primary invasive breast cancers and 35 normal control tissues. MIF was upregulated in breast cancer versus normal tissue (median IRS = 8 versus 6). MIF expression showed positive correlations with progesterone (p = 0.006) and estrogen (p = 0.028) receptor expression, markers of a favourable prognosis and a negative correlation to tumour size (p = 0.007). In line with these data, disease-specific overall (OS) as well as recurrence-free (RFS) survival was significantly improved in breast cancer patients with abundant cytosolic MIF expression compared to MIF low expressers (5-year OS = 67% versus 50%, p = 0.0019; 5-year RFS = 52% versus 36%, p = 0.0327).ConclusionWe conclude that intracellular expression of MIF in breast cancer cells is beneficial, whereas extracellular MIF may play a pro-oncogenic role in promoting breast cancer cell-stroma interactions.

Dataset Information

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 TNF? in women with breast cancer.

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure