title: A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma.
abstract: We have performed association studies between a novel coding single nucleotide polymorphism (D104N) in endostatin, one of the most potent inhibitors of angiogenesis, and prostate cancer. We observed that heterozygous N104 individuals have a 2.5 times increased chance of developing prostate cancer as compared with homozygous D104 subjects (odds ratio, 2.4; 95% confidence interval, 1.4-4.16). Modeling of the endostatin mutant showed that the N104 protein is stable. These results together with the observation that residue 104 is evolutionary conserved lead us to propose that: (a) the DNA segment containing this residue might contain a novel interaction site to a yet unknown receptor; and (b) the presence of N104 impairs the function of endostatin.
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Biologia, Instituto de Biociências, USP, São Paulo 05508-900, Brasil.
authors.forename: P
authors.initials: P
authors.lastname: Iughetti
authors.forename: O
authors.initials: O
authors.lastname: Suzuki
authors.forename: P H
authors.initials: PH
authors.lastname: Godoi
authors.forename: V A
authors.initials: VA
authors.lastname: Alves
authors.forename: A L
authors.initials: AL
authors.lastname: Sertié
authors.forename: T
authors.initials: T
authors.lastname: Zorick
authors.forename: F
authors.initials: F
authors.lastname: Soares
authors.forename: A
authors.initials: A
authors.lastname: Camargo
authors.forename: E S
authors.initials: ES
authors.lastname: Moreira
authors.forename: C
authors.initials: C
authors.lastname: di Loreto
authors.forename: C A
authors.initials: CA
authors.lastname: Moreira-Filho
authors.forename: A
authors.initials: A
authors.lastname: Simpson
authors.forename: G
authors.initials: G
authors.lastname: Oliva
authors.forename: M R
authors.initials: MR
authors.lastname: Passos-Bueno
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D003094:Collagen / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D043169:Endostatins; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen