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Annals of Oncology Advance Access originally published online on September 5, 2007
Annals of Oncology 2007 18(12):1990-1994; doi:10.1093/annonc/mdm361
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© 2007 European Society for Medical Oncology

gastrointestinal tumors

Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer

A. Försti1,2,*, H. Lei1,§, B. Tavelin3, K. Enquist4, R. Palmqvist5, A. Altieri1, G. Hallmans4, K. Hemminki1,2 and P. Lenner3

1 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
2 Center for Family and Community Medicine, Karolinska Institute, Huddinge
3 Department of Oncology, Norrlands University Hospital
4 Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University
5 Department of Medical Biosciences, Umeå University, Umeå, Sweden

* Correspondence to: Asta Försti, German Cancer Research Center, Division of Molecular Genetic Epidemiology C050, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. Tel: +49-6221-421803; Fax: +49-6221-421810; E-mail: a.foersti{at}dkfz.de

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.

Patients and 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.

Key words: colorectal cancer, PAI-1, prognostic biomarker, single nucleotide polymorphism, uPA system

§ Current address: Department of Cell Biology, Harvard Medical School, Boston, USA

Received for publication March 30, 2007. Revision received June 18, 2007. Accepted for publication June 19, 2007.


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