Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients

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 ageand 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). 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.

Association of p53 codon 72 polymorphism with liver metastases of colorectal cancers positive for p53 overexpression

Objective： To evaluate the association between p53 codon 72 polymorphism （R72P） and the risk ofcolorectal liver metastases. Methods： The p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer. Results： The R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases （P=0.075）. Carriers of the 72R allele had a 2.25-fold （95% CI （confidence interval）=1.05-4.83） increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold （95% CI=1.02-11.72） and a 1.05-fold （95% CI=0.36-3.08） increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively. Conclusion： These results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.