Effects of FGFR4 G388R, V10I polymorphisms on the likelihood of cancer

Tao Peng,Xiaoli Zhou,Yuanyuan Mi,Wei Yuan,Li Shi,Hao Wu,Ze Zhang,Yangyang Sun,Zhiwei Lv,Li Zuo,Wei Zhang,Quanxin Su,Li-Feng Zhang

doi:10.1038/s41598-020-80146-y

Abstract

The correlation between G388R or V10I polymorphisms of fibroblast growth factor receptor (FGFR) 4 gene and the risk of carcinoma has been investigated previously, but the results are contradictory. Odds ratios (ORs) with 95% confidence intervals (95%CIs), in silico tools, and immunohistochemical staining (IHS) were adopted to assess the association. In total, 13,793 cancer patients and 16,179 controls were evaluated in our pooled analysis. Summarization of all the studies showed that G388R polymorphism is associated with elevated susceptibility to cancer under homozygous comparison (OR = 1.21, 95%CI = 1.03–1.43, P = 0.020) and a recessive genetic model (OR = 1.21, 95%CI = 1.04–1.41, P = 0.012). In the stratification analysis by cancer type and ethnicity, similar findings were indicated for prostate cancer, breast cancer, and individuals of Asian descendant. Polyphen2 bioinformatics analysis showed that the G388R mutation is predicted to damage the protein function of FGFR4. IHS analysis indicated that FGFR4 expression is increased in advanced prostate cancer. These findings may guide personalized treatment of certain types of cancers. Up-regulation of FGFR4 may be related to a poor prognosis in prostate cancer.

Highlights

The correlation between G388R or V10I polymorphisms of fibroblast growth factor receptor (FGFR) 4 gene and the risk of carcinoma has been investigated previously, but the results are contradictory
25 eligible articles concerning Fibroblast growth factor receptor 4 (FGFR4) G388R or V10I polymorphisms were included in our pooled analysis
Data were collected on 29,972 participants (13,793 cancer subjects and 16,179 controls) from 30 case–control studies on FGFR4 G388R polymorphism

Summary

Introduction

The correlation between G388R or V10I polymorphisms of fibroblast growth factor receptor (FGFR) 4 gene and the risk of carcinoma has been investigated previously, but the results are contradictory. In the stratification analysis by cancer type and ethnicity, similar findings were indicated for prostate cancer, breast cancer, and individuals of Asian descendant. IHS analysis indicated that FGFR4 expression is increased in advanced prostate cancer. These findings may guide personalized treatment of certain types of cancers. The etiology underlying cancer development is far from comprehensively demonstrated[1]. Gene mutations, such as single nucleotide polymorphism (SNP), have been indicated in recent years to have an impact on the susceptibility of c ancer[2,3]

Methods

Results

Conclusion