title: Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients.
abstract: OBJECTIVE
  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 χ(2) 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 χ(2) 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 (χ(2) = 3.589, P = 0.166) and alleles (χ(2) = 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 χ(2) = 5.449, P = 0.020), well differentiated (log rank χ(2) = 12.798, P = 0.000), T1 or T2 stage (log rank χ(2) = 4.745, P = 0.029), without lymph node involvement (log rank χ(2) = 6.647, P= 0.010), and at an early clinical stage (log rank χ(2) = 4.615, P = 0.032).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Shen
authors.forename: Ya-Chao
authors.initials: YC
authors.lastname: Lu
authors.forename: Dan-Ping
authors.initials: DP
authors.lastname: Shen
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Liu
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Su
authors.forename: Guan-Shan
authors.initials: GS
authors.lastname: Zhu
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Yin
authors.forename: Xing-Zhi
authors.initials: XZ
authors.lastname: Ni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D051519:Fibroblast Growth Factor 4 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D047368:Tumor Burden; D055815:Young Adult
chemical_list: C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4
keywords: Fibroblast growth factor receptor 4; Gastric cancer; Genetic susceptibility; Gly388Arg; Single nucleotide polymorphism
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