Functional Foxp3 polymorphisms and the susceptibility to cancer

Abstract

Background:Forkhead box P3 (Foxp3) plays important roles in the development and pathogensis of cancer. To investigate the association of 3 polymorphisms of Foxp3 (rs3761548, rs 3761549 and rs2280883) and cancer risk, an updated meta-analysis was performed.Methods:Around 11 studies including 4344 cancer patients and 4665 healthy controls were selected for this meta-analysis. There were nine studies with 3783 cases and 4096 controls for rs3761548, 4 studies with 1669 cases and 1613 controls for rs3761549 and 4 studies with 1821 cases and 1799 controls for rs2280883. Odds radios (ORs) and 95% confidence intervals (CIs) were used to evaluate the cancer risk.Results:Meta-analysis showed that rs3761548 was associated with an increased cancer risk in the overall population under the recessive model (AA vs CA + CC: OR = 1.45, 95%CI = 1.03–2.02, P = .03). No association was found between rs3761549, rs2280883 polymorphisms, and cancer susceptibility in the overall population. Nonetheless, in the genotyping methods subgroup analysis of rs2280883, a lower risk of cancer was found in studies using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) under the allelic model (C vs T: OR = 0.70, 95%CI = 0.52–0.95, P = .02), heterozygote model (TC vs TT: OR = 0.60, 95%CI = 0.41–0.87, P = .008) and dominant model (CC + TC vs TT: OR = 0.63, 95%CI = 0.45–0.90, P = .01). In the subgroup analysis by cancer types showed C allele or TC carriers were insusceptible to cancer under 3 genetic models (C vs T: OR = 0.78, 95%CI = 0.64–0.95, P = .01; TC vs TT: OR = 0.50, 95%CI = 0.32–0.79, P = .003; CC + TC vs TT: OR = 0.64, 95%CI = 0.51–0.82, P < .001).Conclusion:Our results suggest that rs3761548 polymorphism is associated with cancer risk.

Associations of FOXP3 gene polymorphisms with susceptibility and severity of preeclampsia: A meta‐analysis

“…The rs2280883, located in intron nine near a conserved transcription region of FOXP3, was indicated to possibly create an alternative splice site and hence to have definite effect on the mRNA level and function of this gene. 46,47 However, no correlation was observed between this polymorphism and PE risk according to present results. The reason might be that the total sample size was limited, which might mask its actual relationship with this polymorphism.…”

“…As for the FOXP3 rs4824747 and rs3761547 polymorphisms, we did not observe any associations between these two polymorphisms and susceptibility of PE. The rs2280883, located in intron nine near a conserved transcription region of FOXP3 , was indicated to possibly create an alternative splice site and hence to have definite effect on the mRNA level and function of this gene 46,47 . However, no correlation was observed between this polymorphism and PE risk according to present results.…”

Association Between LncRNA MALAT1 Polymorphisms and Cancer Risk: A Meta-Analysis Based on7007 Cases and 8791 Controls

“…The heterogeneity among studies was detected by Cochran Q test and I 2 test [23]. The xed effects model was used to calculate the pooled OR of studies when the P value of heterogeneity test was > 0.1 (P > 0.10) or I 2 was < 50%; if not, the random effects model was applied [22,24]. The publication bias was assessed by Funnel plot, egger's test and sensitivity analysis.…”

“…The studies without controls and reviews were excluded. The smaller sample size was excluded when two or more studies had overlapped subjects [22,23].…”

Haplotypes of FOXP3 genetic variants are associated with susceptibility, autoantibodies, and TGF-β1 in patients with systemic lupus erythematosus

“…Different single nucleotide variants (SNVs) have been described in the promoter region of FOXP3 , which can affect the expression of FoxP3 and impair the Treg cells differentiation and function 19 . The -924 G > A (rs2232365) and -3279 C > A (rs3761548) FOXP3 variant were associated with the susceptibility and prognosis of various autoimmune diseases, such as rheumatoid arthritis 20 , 21 , multiple sclerosis 22 , and SLE 8 .…”