Published online Jul 28, 2013. doi: 10.3748/wjg.v19.i28.4568
Revised: March 21, 2013
Accepted: March 28, 2013
Published online: July 28, 2013
Processing time: 202 Days and 16.8 Hours
AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival.
METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 age- and sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC.
RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ2 = 3.589, P = 0.166) and alleles (χ2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ2 = 5.449, P = 0.020), well differentiated (log rank χ2 = 12.798, P = 0.000), T1 or T2 stage (log rank χ2 = 4.745, P = 0.029), without lymph node involvement (log rank χ2 = 6.647, P= 0.010), and at an early clinical stage (log rank χ2 = 4.615, P = 0.032).
CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.
Core tip: This study investigated the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and any associations between this polymorphism and clinicopathological parameters such as age, gender, clinical stage, tumor grade, human epidermal growth factor receptor 2 status and survival. The results suggested that the FGFR4 Gly388Arg polymorphism was not a risk factor for GC cancer initiation but that it was a useful prognostic marker for GC patients when the tumor was relatively small, well differentiated, or at an early clinical stage.