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

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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.

Lei, H (författare)
Tavelin, BjörnNorrlands University Hospital(Swepub:umu)bjta0001 (författare)
Enquist, KUmeå universitet,Näringsforskning (författare)
Palmqvist, RichardUmeå universitet,Patologi(Swepub:umu)ripa0001 (författare)
Altieri, A (författare)
Hallmans, Göran,1947-Umeå universitet,Näringsforskning(Swepub:umu)goha0001 (författare)
Hemminki, K (författare)
Lenner, PerNorrlands University Hospital(Swepub:umu)pele0005 (författare)
Norrlands University HospitalNäringsforskning (creator_code:org_t)

Ingår i:Annals of Oncology: Oxford University Press18:12, s. 1990-19940923-75341569-8041

Av författaren/redakt...: Försti, A; Lei, H; Tavelin, Björn; Enquist, K; Palmqvist, Richa ...; Altieri, A; visa fler...; Hallmans, Göran, ...; Hemminki, K; Lenner, Per; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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