Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand-induced tyrosine kinase activity. The Glycine (Gly) to Arginine (Arg) polymorphism at codon 388 (Gly388Arg), which encodes an amino acid in the transmembrane part of the FGFR4 gene, was reported to be associated with an increased risk in some carcinomas. We investigated the association between the Gly388Arg polymorphism or the G or A polymorphism at intron 11 (rs2011077) of FGFR4, which was located 1,213 base pairs apart from the Gly388Arg polymorphism, and the risk of prostate cancer or benign prostate hyperplasia (BPH), and the prostate cancer disease status in Japanese men. Genotypes of Gly388Arg and rs2011077 polymorphisms of FGFR4 were determined in 492 patients with prostate cancer, 165 patients with BPH and 179 male controls. Regarding the Gly388Arg polymorphism, individuals with the ArgArg genotype had a 2.207- and 1.958-fold increased risk of prostate cancer and BPH, and a 1.804-fold increased risk of metastatic prostate cancer compared with those with the GlyGly genotype. Regarding the rs2011077 polymorphism, individuals with the GG genotype had a 6.260- and 3.033-fold increased risk of prostate cancer and BPH, and a 5.550-fold increased risk of metastatic prostate cancer compared with those with the AA genotype. Our results indicate that the FGFR4 Arg allele of the Gly388Arg polymorphism and the G allele of the rs2011077 polymorphism have a significant impact on the development of prostate cancer and BPH, and the progression of prostate cancer in a Japanese population.
(c) 2008 Wiley-Liss, Inc.