title: Combined analysis of EGF+61G>A and TGFB1+869T>C functional polymorphisms in the time to androgen independence and prostate cancer susceptibility.
abstract: Proliferative mechanisms involving the epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta(1)) ligands are potential alternative pathways for prostate cancer (PC) progression to androgen independence (AI). Thus, the combined effect of EGF and TGFB1 functional polymorphisms might modulate tumor microenvironment and consequently its development. We studied EGF+61G>A and TGFB1+869T>C functional polymorphisms in 234 patients with PC and 243 healthy individuals. Intermediate- and high-proliferation genetic profile carriers have increased risk for PC (odds ratio (OR)=3.76, P=0.007 and OR=3.98, P=0.004, respectively), when compared with low proliferation individuals. Multivariate analysis showed a significantly lower time to AI in the high proliferation group, compared with the low/intermediate proliferation genetic profile carriers (HR=2.67, P=0.039), after adjustment for age, metastasis and stage. Results suggest that combined analysis of target genetic polymorphisms may contribute to the definition of cancer susceptibility and pharmacogenomic profiles. Combined blockage of key molecules in proliferation signaling pathways could be one of the most promising strategies for androgen-independent prostate cancer.
authors.affiliation: Molecular Oncology Group-CI and Department of Virology, Portuguese Institute of Oncology, Porto Centre, 4200-072 Porto, Portugal.
authors.forename: A L
authors.initials: AL
authors.lastname: Teixeira
authors.forename: R
authors.initials: R
authors.lastname: Ribeiro
authors.forename: A
authors.initials: A
authors.lastname: Morais
authors.forename: F
authors.initials: F
authors.lastname: Lobo
authors.forename: A
authors.initials: A
authors.lastname: Fraga
authors.forename: F
authors.initials: F
authors.lastname: Pina
authors.forename: F M
authors.initials: FM
authors.lastname: Calais-da-Silva
authors.forename: F E
authors.initials: FE
authors.lastname: Calais-da-Silva
authors.forename: R
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000368:Aged; D000728:Androgens / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016017:Odds Ratio; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018570:Risk Assessment; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D000728:Androgens; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor