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A polymorphism in endostatin, an angiogenesis inhibitor, predisposes for the development of prostatic adenocarcinoma.

Iughetti P., Suzuki O., Godoi P.H., Alves V.A., Sertie A.L., Zorick T., Soares F., Camargo A.A., Moreira E.S., di Loreto C., Moreira-Filho C.A., Simpson A., Oliva G., Passos-Bueno M.R.

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.

Cancer Res. 61:7375-7378(2001) [PubMed] [Europe PMC]

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