Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer.
BACKGROUND
Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor cancer prognosis. We examined four single nucleotide polymorphisms (SNPs) with a potential effect on expression of genes in the uPA system for their role in colorectal cancer susceptibility and prognosis.


METHODS
We genotyped the SNPs in 308 Swedish incident colorectal cancer patients with up to 16 years of follow-up and in 585 age- and sex-matched controls. We evaluated the associations between genotypes and colorectal cancer and Dukes' stage. Survival probabilities were compared between different subgroups.


RESULTS
Patients with PAI-1 -675 5G/5G genotype had better survival than patients with 4G/4G or 4G/5G genotypes when they had Dukes' stage A or B tumors (P = 0.023 and P = 0.015, respectively). No statistically significant association was observed between the SNPs and the risk of colorectal cancer or Dukes' stage.


CONCLUSIONS
Our results suggest a role for the PAI-1 genotype in colorectal cancer prognosis, but further studies are needed to evaluate the impact of our finding in the clinic.
Försti
A
A
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. a.foersti@dkfz.de
Lei
H
H
Tavelin
B
B
Enquist
K
K
Palmqvist
R
R
Altieri
A
A
Hallmans
G
G
Hemminki
K
K
Lenner
P
P
D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D013548:Sweden; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism