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 -794CATT 5-8 (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 CATT 5-8 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 CATT 5-8 , respectively, without significant differences in both groups. Nevertheless, the women with BC carriers -173*C and -794CATT 7 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 -794CATT 7 are associated with the increase of MIF circulating in women with BC.

Macrophage migration inhibitory factor gene polymorphisms (SNP ‐173 G>C and STR‐794 CATT5‐8) confer risk of plaque psoriasis: A case–control study

“…Nevertheless, we studied circulating levels of MIF and found a relationship between this allele and higher serum levels of MIF in patients with psoriasis. This finding agrees with previous observations 17 , 32 , 33 , 34 and supports the functional effect of this polymorphism, which has been related to a binding site for protein activator‐4 (AP4) that increases promoter activity of MIF . 35 …”

ICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus

“…Human genetic data supporting the notion of a pathogenic role of high-expression MIF alleles in autoimmune inflammatory conditions (6)(7)(8)35,36), infectious diseases (37)(38)(39)(40), and cancers (41)(42)(43) have focused attention on the transcriptional regulation of the variant promoter -794 CATT 5-8 microsatellite. The transcription factor ICBP90 was discovered to be essential for the -794 CATT 5-8 length-dependent regulation of MIF transcription and to mediate inflammatory stimulation in different immune and stromal cell types (11).…”

Haplotypes of [‐794(CATT)5–8/‐173G>C] MIF gene polymorphisms and its soluble levels in cutaneous squamous cell carcinoma in western Mexican population

“…Two functional polymorphisms have been located in the promoter region of the MIF gene, the first polymorphism is a CATT short‐tandem repeat (STR) at position ‐794, with five‐ to eight‐length variants (alleles 5–8), in which the number of repeats of CATT is associated with varying amounts of serum circulating levels of MIF (Donn et al, 2002). In fact, the variants with the higher repetitions (CATT) 6–8 show higher circulating MIF levels (Avalos‐Navarro et al, 2020). The second promoter polymorphism is a single nucleotide polymorphism (SNP) in the position ‐173 and consists of a transversion of G>C which has been associated with increased MIF gene expression and protein levels (Llamas‐Covarrubias et al, 2013).…”