Involvement of FGFR4 Gene Variants on the Clinicopathological Severity in Urothelial Cell Carcinoma.

Ming-Dow Tsay,Chia-Yi Lee,Ming-Ju Hsieh,Shun-Fa Yang,Chia-Yen Lin,Sheng-Chun Hung,Chuan-Shu Chen,Shian-Shiang Wang

doi:10.3390/ijerph17010129

Abstract

Fibroblast growth factor receptor 4 (FGFR4) plays a prominent role in cell proliferation and cancer progression. This study explored the effect of FGFR4 single-nucleotide polymorphisms (SNPs) on the clinicopathological characteristics of urothelial cell carcinoma (UCC). This study was conducted to survey the possible correlation of the polymorphism of FGFR4 to the risk and clinicopathologic characteristics of UCC. Four loci of FGFR4 (rs2011077 T > C, rs351855 G > A, rs7708357 G>A, and rs1966265 A > G) were genotyped via the TaqMan allelic discrimination approach in 428 UCC cases and 856 controls. The results indicated that UCC subjects who carried the SNP rs2011077 TC+CC genotypes were significantly related to a higher tumor stage (odds ratio (OR): 1.751, 95% confidence interval (CI): 1.078–2.846), primary tumor size (OR: 1.637, 95% CI: 1.006–2.662), and histopathologic grading (OR: 1.919, 95% CI: 1.049–3.511). Moreover, the SNP rs1966265 AG+GG genotypes were prominently related to a higher tumor stage (OR: 1.769, 95% CI: 1.082–2.891), primary tumor size (OR: 1.654, 95% CI: 1.011–2.706), and histopathologic grading (OR: 2.006, 95% CI: 1.096–3.674) compared to individuals with AA homozygotes. In conclusion, our data reveal association of FGFR4 polymorphisms with UCC clinicopathologic characteristics. FGFR4 polymorphisms may serve as a marker or therapeutic target in UCC development.

Highlights

Urothelial cell carcinoma (UCC) refers to the malignant neoplasm that develops from the transitional epithelia, which includes the tissue in the renal pelvis, ureter, and bladder [1]
The patients with UCC presented with early tumor stage concerning whole tumor stage, tumor T status, lymph node status, and existence of metastasis, while high histopathological grading was observed in the study group
The results demonstrated that the existence of at least one allele of single-nucleotide polymorphisms (SNPs) rs2011077 (TC and CC) was related to a significantly higher tumor stage (odds ratio (OR): 1.751, 95% confidence interval (CI): 1.078–2.846, P = 0.023), larger primary tumor size (OR: 1.637, 95% CI: 1.006–2.662, P = 0.046) and higher histopathologic grading (OR: 1.919, 95% CI: 1.049–3.511, P = 0.032) (Table 3)