Abstract:
:Increasing evidence shows that inflammation plays critical roles in the tumorigenesis of bladder cancer. Fibroblast growth factor 12 (FGF12), a kind of inflammatory cytokine, is located in the region of 3q28 that has been demonstrated to be a bladder cancer risk locus by genome wide association study (GWAS). In this study, we aimed to investigate the association of GWAS signal rs710521 and rs884309 and rs1464938 in the promoter of FGF12 with the risk of bladder transitional cell carcinoma (TCC). The polymorphisms were analyzed by using a Taqman assay in 331 TCC patients and 516 age-, gender-, and ethnicity-matched controls. The expression levels of FGF12 mRNA were examined in TCC and non-cancerous normal tissues by using quantitative real-time PCR and the luciferase activity was determined by using the Dual-Luciferase Assay System. The rs1464938 AA genotype and A allele were associated with a significantly increased risk of TCC (AA vs. GG: adjusted OR = 2.54, 95% CI, 1.49-4.35, P < 0.001; AA vs. AG/GG: adjusted OR = 2.25, 95% CI, 1.36-3.71, P = 0.002; A vs. G: adjusted OR = 1.44, 95% CI, 1.15-1.80, P = 0.001, respectively). Haplotype analysis showed that rs884309G- rs1464938A haplotype was associated with an increased risk of TCC (OR = 1.61, 95% CI, 1.23-2.11, P = 0.001). Functional analysis showed that the rs1464938 AG/AA genotypes exhibited higher levels of FGF12 mRNA in TCC tissues and the rs1464938 A allele enhanced FGF12 promoter activity (P < 0.05). These findings suggest that the rs1464938 A allele at the 3q28 locus contribute to the development of TCC by regulating FGF12 expression levels.
journal_name
Cytokinejournal_title
Cytokineauthors
Wu J,Huang H,Huang Q,Qiu R,Huang M,Meng Ddoi
10.1016/j.cyto.2020.155294subject
Has Abstractpub_date
2020-12-01 00:00:00pages
155294eissn
1043-4666issn
1096-0023pii
S1043-4666(20)30310-0journal_volume
136pub_type
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