FGFR4 transmembrane domain polymorphism and cancer risk: a meta-analysis including 8555 subjects

Fibroblast growth factor receptor 4 (FGFR4), belonging to the receptor tyrosine kinase family, is involved in cancer initiation and progression. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor was shown to contribute to genetic susceptibility to cancer but the results were inconsistent. We performed a meta-analysis using 12 eligible case-control studies with a total of 4892 patients and 3663 controls to summarise the data on the association between the FGFR4 Gly388Arg polymorphism and cancer risks. The overall odds ratio (OR) with a 95% confidence interval (CI) showed statistical association between the FGFR4 Gly388Arg polymorphism and cancer risks under homozygote comparison, allele contrast and the recessive genetic model. In the subgroup analysis by ethnicity, statistically significantly increased cancer risks were found among Asians for homozygote comparison (OR = 1.43, 95% CI = 1.13-1.80, P(heterogeneity)=0.24), allele contrast (OR = 1.16, 95% CI = 1.04-1.29, P(heterogeneity) = 0.25) and the recessive genetic model (OR = 1.47, 95% CI = 1.19-1.81, P(heterogeneity) = 0.15). In the subgroup analysis for different tumour types, Arg(388) allele had an effect of increasing the risks of breast (homozygote comparison OR = 1.57, 95% CI = 1.04-2.37, P(heterogeneity) = 0.83 and the recessive model OR = 1.51, 95% CI = 1.02-2.24, P(heterogeneity) = 0.80) and prostate cancer (Gly/Arg versus Gly/Gly: OR = 1.16, 95% CI = 1.02-1.32, P(heterogeneity)=0.74; Arg versus Gly: OR = 1.17, 95% CI = 1.07-1.29, P(heterogeneity) = 0.18 and the dominant model: OR = 1.20, 95% CI = 1.06-1.35, P(heterogeneity) = 0.89). Our meta-analysis suggests that the FGFR4 Gly388Arg polymorphism most likely contributes to susceptibility to cancer, especially in Asians. Besides, the Arg(388) allele might be associated with increased risks of breast and prostate cancer.