BACKGROUND/AIMS: The roles of urokinase-type plasminogen activator (uPA) expression in tumor occurrence, invasion and prognosis have been established. However, how uPA genetic polymorphisms influence the occurrence and outcome of tumors is not as clear. METHODOLOGY: We conducted a case-control study based on previously stored peripheral blood samples from 237 gastric cancer patients and 242 healthy controls. uPA exon 6 and intron 7 genotypes were determined by direct DNA sequencing. Logistic regression analyses and Cox proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features, and survival. RESULTS: uPA exon 6 C/T and intron 7 T/C polymorphisms did not correlate well with gastric cancer susceptibility. uPA exon 6 T/C and T/T genotypes were associated with venous invasion and lymphatic invasion, but not with stage, serosal invasion or lymph node metastasis. uPA intron 7 T/C polymorphism did not correlate well with invasive phenotype of gastric cancer. On Cox proportional hazards analyses, uPA exon 6 and intron 7 polymorphisms were not independent prognostic factors for survival. CONCLUSIONS: uPA exon 6 C/T polymorphism is associated with invasive phenotype of gastric cancer, but not with susceptibility or survival of gastric cancer. uPA intron 7 is a silent polymorphism.
BACKGROUND/AIMS: The roles of urokinase-type plasminogen activator (uPA) expression in tumor occurrence, invasion and prognosis have been established. However, how uPA genetic polymorphisms influence the occurrence and outcome of tumors is not as clear. METHODOLOGY: We conducted a case-control study based on previously stored peripheral blood samples from 237 gastric cancerpatients and 242 healthy controls. uPA exon 6 and intron 7 genotypes were determined by direct DNA sequencing. Logistic regression analyses and Cox proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features, and survival. RESULTS:uPA exon 6 C/T and intron 7 T/C polymorphisms did not correlate well with gastric cancer susceptibility. uPA exon 6 T/C and T/T genotypes were associated with venous invasion and lymphatic invasion, but not with stage, serosal invasion or lymph node metastasis. uPAintron 7 T/C polymorphism did not correlate well with invasive phenotype of gastric cancer. On Cox proportional hazards analyses, uPA exon 6 and intron 7 polymorphisms were not independent prognostic factors for survival. CONCLUSIONS:uPA exon 6 C/T polymorphism is associated with invasive phenotype of gastric cancer, but not with susceptibility or survival of gastric cancer. uPA intron 7 is a silent polymorphism.
Authors: Stefania Nobili; Lorenzo Bruno; Ida Landini; Cristina Napoli; Paolo Bechi; Francesco Tonelli; Carlos A Rubio; Enrico Mini; Gabriella Nesi Journal: World J Gastroenterol Date: 2011-01-21 Impact factor: 5.742