title: Plasminogen activator inhibitor-1 gene polymorphism and colorectal cancer risk and prognosis.
abstract: Plasminogen activator inhibitor-1 (PAI-1) is a factor in urokinase-type plasminogen activator proteolytic system, which is important for tumour invasion and metastasis. Elevated PAI-1 levels in tumours are associated with poor prognosis. An insertion/deletion (4G/5G) promoter polymorphism in the PAI-1 gene affects activity of its product, the 4G/4G genotype being related to higher transcription levels. We assessed the association between the polymorphism and colorectal cancer risk in 206 cancer patients and 355 healthy controls. The results indicated that the PAI-1 gene polymorphism did not affect colorectal cancer risk. Nevertheless, within the case group, the 4G/4G genotype was associated with more advanced tumours (Dukes' C&D), whereas the 5G/5G homozygocity was associated with the Dukes' A&B tumours. The association with the 4G/4G presence was stronger in patients with proximal colon cancers (odds ratio= 6.02, 95% confidence interval, 1.15-31.54). Our results suggest that PAI-1 genotype may be a useful prognostic marker for colorectal cancer, however further specifically designed studies are needed to assess its value in this respect.
authors.affiliation: MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK. asl@mrc-dunn.cam.ac.uk
authors.forename: Alexandre
authors.initials: A
authors.lastname: Loktionov
authors.forename: Mark A
authors.initials: MA
authors.lastname: Watson
authors.forename: William S L
authors.initials: WS
authors.lastname: Stebbings
authors.forename: Chris T M
authors.initials: CT
authors.lastname: Speakman
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Bingham
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics; D000368:Aged; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D004739:England / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology; D014158:Transcription, Genetic
chemical_list: D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1