The association ofFOXP3gene polymorphisms with cancer susceptibility: a comprehensive systemic review and meta-analysis

Abstract

The role of forkhead box P3 (FOXP3) protein in tumorigenesis has long been controversial and existing data on the association between FOXP3 gene polymorphisms and cancer susceptibility were inconsistent. Here, we conducted a meta-analysis to better clarify the relationship. A comprehensive search of studies published from July 2008 to June 2018 was conducted. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were performed using the Revman 5.2 software. A total of 12 articles with 19 case–control studies and 10389 participants were included. Three FOXP3 polymorphisms and six cancer types were evaluated. While no significant results were observed in overall and breast cancer groups for rs3761548 (A/C) polymorphisms, the pooled data showed an elevated risk of cancer in variant AA genotypes and A allele for Chinese population (AA vs. AC+CC: OR = 1.61, 95% CI = 1.09, 2.39; AA vs. CC: OR = 1.74, 95% CI = 1.05, 2.89; A vs. C: OR = 1.34, 95% CI = 1.00, 1.78). Neither the overall group analyses nor the subgroup analyses stratified by cancer type and ethnicity proposed any significant association of rs2280883 (C/T) and rs3761549 (T/C) polymorphisms with cancer susceptibility. This meta-analysis suggested that FOXP3 rs3761548 (A/C) polymorphisms were associated with increased cancer risk in Chinese population while rs2280883 (C/T) and rs3761549 (T/C) polymorphisms were not. More large-sample researches with diverse ethnicities and cancer types are needed to draw a concrete conclusion.

Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: A retrospective case‐control study

“…15 FOXP3 is encoded by FOXP3 (Scurfin) gene (Gene ID: 50943, MIM #300292), and acts both as an activator of transcription for Treg cells development, and as a transcriptional repressor in downregulating cytokine expression. 16,17 FOXP3 gene is located on chromosome Xp11.23, 17 and several FOXP3 polymorphisms associated with different diseases, particularly those associated with altered immunity, were reported. These include systemic lupus erythematosus, 18,19 Grave's disease, 20,21 type 1 (autoimmune) diabetes mellitus, and allergic rhinitis, 22,23 and pregnancy complications, including preeclampsia, 24,25 and RPL.…”

“…FOXP3 is encoded by FOXP3 ( Scurfin ) gene (Gene ID: 50943, MIM #300292), and acts both as an activator of transcription for Treg cells development, and as a transcriptional repressor in downregulating cytokine expression 16,17 . FOXP3 gene is located on chromosome Xp11.23, 17 and several FOXP3 polymorphisms associated with different diseases, particularly those associated with altered immunity, were reported.…”

Forkhead box F2 as a novel prognostic biomarker and potential therapeutic target in human cancers prone to bone metastasis: a meta-analysis

“…Because of these limitations, the current outcomes should be interpreted with caution and the conclusions of this meta-analysis require detailed consideration. [60][61][62] In conclusion. this current systematic review and meta-analysis demonstrated that FOXF2 may be a clinically important prognostic factor for patients with various types of cancer prone to bone metastasis.…”

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

“…As an important component of the tumour microenvironment, Tregs are responsible for the downregulation of autoimmune reactions and promotion of immunological tolerance. Recent studies on the roles of Tregs in tumours have demonstrated that the regulatory mechanisms mediated by Tregs contribute to immune evasion against tumour immunotherapy 10 . Therefore, FOXP3 is an essential factor that induces and maintains the unique immunosuppressive properties of Tregs.…”

“…Recent studies on the roles of Tregs in tumours have demonstrated that the regulatory mechanisms mediated by Tregs contribute to immune evasion against tumour immunotherapy. 10 Therefore, FOXP3 is an essential factor that induces and maintains the unique immunosuppressive properties of Tregs.…”