MIF -173 G>C polymorphism as a context-dependent modifier of solid cancer risk: A meta-analysis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in immune regulation and cancer development. A functional promoter polymorphism in MIF (-173 G>C; rs755622) has been investigated for its association with cancer susceptibility, but results remain inconsistent across populations and tumor types. METHODS: To evaluate the association between the MIF -173 G>C polymorphism and susceptibility to solid cancers, the PubMed, Scopus, and ProQuest databases were searched for case-control studies on MIF and solid cancer risk. Associations between MIF -173 G>C polymorphisms and solid cancer susceptibility were assessed using random-effects models, with subgroup analyses by ethnicity and cancer type. RESULTS: Seventeen studies were identified, contributing 17 independent comparisons with 7678 participants (3680 cases, 3998 controls). The -173C allele was associated with a modest increase in solid cancer susceptibility under the dominant (OR 1.26, 95%CI: 1.02-1.56) and allelic (OR 1.26, 95%CI: 1.04-1.52) models, while the recessive model was not statistically significant. Subgroup analyses revealed stronger and consistent risk associations in Far Eastern populations in all models. Gastrointestinal cancers demonstrated significant associations under all three models, but no significant association was observed in breast cancer. Although formal tests for subgroup differences were not statistically significant CONCLUSIONS: MIF -173 G>C polymorphisms influence cancer susceptibility in a context-dependent manner, with stronger effects in Far Eastern populations and gastrointestinal cancers, though these subgroup patterns warrant confirmation in larger, adequately powered studies. (PROSPERO, ID: CRD420251207775).