A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma.
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.
Iughetti
P
P
Centro de Estudos do Genoma Humano, Departamento de Biologia, Instituto de Biociências, USP, São Paulo 05508-900, Brasil.
Suzuki
O
O
Godoi
P H
PH
Alves
V A
VA
Sertié
A L
AL
Zorick
T
T
Soares
F
F
Camargo
A
A
Moreira
E S
ES
di Loreto
C
C
Moreira-Filho
C A
CA
Simpson
A
A
Oliva
G
G
Passos-Bueno
M R
MR
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
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen