Abstract
Fibroblast growth factor receptor 4 (FGFR4) is a member of receptor tyrosine kinase family. A functional Gly388Arg (rs351855 G>A) polymorphism in FGFR4 gene causes a glycine-to-arginine change at codon 388 within the transmembrane domain of the receptor. Although the FGFR4 rs351855 G>A polymorphism has been implicated in cancer development, its association with cancer risk remains controversial. Here, we have systematically analyzed the association between the rs351855 G>A polymorphism and cancer risk by performing a meta-analysis of 27 studies consisting of 8,682 cases and 9,731 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. The rs351855 G>A polymorphism was associated with an increased cancer risk under the recessive model (OR=1.19, 95% CI=1.01-1.41). Stratified analysis by cancer type indicated the rs351855 G>A polymorphism was associated with an increased risk of breast and prostate cancer, but a decreased risk of lung cancer. This meta-analysis demonstrates the FGFR rs351855 G>A polymorphism is associated with increased cancer risk and suggests it could potentially serve as a chemotherapeutic target or biomarker to screen high-risk individuals.
Highlights
Cancer represents an enormous economic burden on society in both developing and developed countries
91 articles were excluded for the following reasons: 1) they were review articles or meta-analyses, 2) they did not investigate association between the Fibroblast growth factor receptor 4 (FGFR4) rs351855 G>A polymorphism and cancer risk, 3) they were not case-control studies, or 4) had no enough data reported to calculate the odds ratios (ORs) and 95% confidence intervals (CIs)
23 articles consisting of 27 individual studies investigated the association between the FGFR4 rs351855 G>A polymorphism and cancer risk, and fit the eligibility criteria (Figure 1)
Summary
Cancer represents an enormous economic burden on society in both developing and developed countries. Cancer is a complex multifaceted disease that results from gene-environment interactions. The binding of ligands to FGFRs triggers several downstream signal transduction cascades that are activated in cancer, including phospholipase C (PLC), phosphatidylinositol 3-kinase (PI3K), signal transducer and activator of transcription (STAT), as well as mitogen-activated protein kinases (MAPKs) [3, 4]. A large scale analysis of 4,853 solid tumors has revealed that 7.1% of cancers harbor FGFR aberrations, including gene amplifications (66%), mutations (26%), and rearrangements (8%) [9]. Different types of FGFR inhibitors have been developed to treat cancer, including multi-target tyrosine kinase inhibitors, FGFR specific tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and FGF ligand traps [2, 10]
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