title: An association between the 4G polymorphism in the PAI-1 promoter and the development of aggressive fibromatosis (desmoid tumor) in familial adenomatous polyposis patients.
abstract: Aggressive fibromatosis is a mesenchymal neoplasm associated with mutations resulting in beta-catenin mediated transcriptional activation. Plasminogen activator inhibitor-1 (PAI-1) is expressed at a high level in aggressive fibromatosis, and using transgenic mice, we found that PAI-1 plays an important role in aggressive fibromatosis tumor formation. Familial adenomatous polyposis is associated with Adenomatous Polyposis Coli gene mutations resulting in beta-catenin mediated transcriptional activation, yet only some patients develop aggressive fibromatosis. Since PAI-1 expression is influenced by a promoter 4G/5G polymorphism, we investigated the incidence of this polymorphism in familial adenomatous polyposis patients who did and who did not develop aggressive fibromatosis, as well as sporadic aggressive fibromatosis patients. There was a trend towards association of the 4G allele (associated with high PAI-1 expression) with the development of aggressive fibromatosis in familial adenomatous polyposis patients (50% vs. 19%, P = 0.1). In familial adenomatous polyposis patients who did not develop aggressive fibromatosis, there was a significantly lower proportion of patients with a 4G allele compared to the healthy control (19% vs. 51%, P = 0.0286). The lower incidence of 4G polymorphism in the PAI-1 promoter may be preventive against the development of aggressive fibromatosis. This data provides additional evidence supporting an important role for PAI-1 in the pathogenesis of aggressive fibromatosis.
authors.affiliation: Program in Developmental Biology, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Li
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Wei
authors.forename: Frank
authors.initials: F
authors.lastname: Baliko
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Alman
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D015984:Causality; D015897:Comorbidity; D018222:Desmoid Tumors / Q000453:epidemiology / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D015533:Transcriptional Activation
chemical_list: D017395:Plasminogen Activator Inhibitor 1