An updated meta-analysis of the association between fibroblast growth factor receptor 4 polymorphisms and susceptibility to cancer

Abstract

Fibroblast growth factor receptor 4 (FGFR4) is a cell surface receptor tyrosine kinases for FGFs. Several studies have focused on the association between FGFR4 polymorphisms and cancer development. This meta-analysis aimed to estimate the association between FGFR4 rs351855 (Gly388Arg), rs1966265 (Val10Ile), rs7708357, rs2011077, and rs376618 polymorphisms and cancer risk. Eligible studies were identified from electronic databases. All statistical analyses were achieved with the STATA 14.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) used to quantitatively estimate the association. Overall, no significant association was found between rs351855, rs2011077, and rs376618 polymorphism with the risk of overall cancer. The rs1966265 polymorphism significantly decreased the risk of cancer in recessive (OR=0.87, 95%CI=0.78-0.97, p=0.009, TT vs CT+CC) genetic model. Whereas the rs7708357 polymorphism was positively associated with cancer risk in dominant (OR=1.17, 95%CI=1.02-1.36, p=0.028) genetic model. Stratified analysis revealed that rs351855 variant significantly increased the risk of prostate cancer in heterozygous (OR=1.16, 95%CI=1.02-1.32, p=0.025 AG vs GG), dominant (OR=1.20, 95%CI=1.06-1.35, p=0.004, AG+AA vs GG), and allele (OR=1.22, 95%CI=1.06-1.41, p=0.005, A vs G) genetic models. In summary, the findings of this meta-analysis indicate that rs1966265, rs7708357 and rs351855 polymorphisms are correlated to cancer development. Further well-designed studies are necessary to draw more precise conclusions.

Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer

“…FGFR4 SNP, rs351855, has been extensively reported for its association with the occurrence, progression, and prognosis of multiple tumor types [28]. This genetic variation (G > A) causes the substitution of glycine by arginine at position 388 in the transmembrane domain of the receptor [19].…”

“…This discrepancy may be, in part, accounted for by variations in the allele frequency of FGFR4 arg388 across the general population of different ethnic groups. It was estimated that FGFR4 arg388 has an allele frequency of ~13% in the African population, roughly 30% in the European and Northeast Asian populations, and nearly 45% in the Latino and Southeast Asian (such as Taiwan) populations [28,31]. As such, rs351855 was often demonstrated to be correlated with clinicopathological features of cancer but not with the occurrence of the disease.…”

Association of the rs1966265 and rs351855 FGFR4 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico

“…When FGFR4 is transphosphorylated, it is activated and induces cell proliferation by stimulating the kinase receptor [ 38 ]. The presence of this arginine stabilizes the protein and prolongs its activity [ 39 ].…”

FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis

“…The recent meta-analysis by Moazeni-Roodi et al. revealed that the FGFR4 rs1966265 C>T polymorphism significantly reduced the risk of cancer in the recessive model (TT vs CT+CC) and the rs7708357 G>A variant was significantly associated with increased cancer development in the dominant model (AG+AA vs GG) ( 32 ). The Y367C FGFR4 mutation in the extracellular juxtamembrane domain promotes the FGFR4 dimerization on the cell surface and thereby leads to ligand-independent activation of downstream signaling pathways ( 73 ).…”