Polymorphism In Endostatin, An Angiogenesis Inhibitor, And Prostate Cancer Risk And Survival: A Prospective Study

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 26 May 2009 - 1:00 PDT

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UroToday.com - Angiogenesis is the process of new blood vessel formation in tumors, facilitating their growth. Endostatin is a cleavage product of collagen and is a potent inhibitor of endothelial cell proliferation and migration. Endostatin causes apoptosis in endothelial and tumor cells. Prostate cancer expresses angiogenic factors.

A missense mutation in the coding region for endostatin has been described, but the polymorphism affects protein conformation rather than protein expression. Cellular assays suggested that the result is impaired endostatin binding to laminin, a basement membrane protein. In an online article in the International Journal of Cancer, Dr. Lorelei Mucci and colleagues present data from the Physicians' Health Study examining the D104N endostatin polymorphism in relation to prostate cancer risk and survival.

The Physicians' Health Study was a randomized trial of aspirin and beta-carotene supplementation among 22,071 physicians ages 40-84 that was initiated in 1982. A total of 14,916 participants had samples available for this nested case-control study. The analysis identified 544 incident prostate cancer cases and 678 controls for polymorphism genotyping.

Among the control men, 84.2% were wildtype homozygous (DD), 14.5% were heterozygous (DN), and 1.3% were homozygous carriers of the rare allele (NN). Carriage of the polymorphic N allele was not associated with risk of total prostate cancer risk. There was no evidence that the endostatin D104N polymorphism was associated with prostate cancers diagnosed at a younger or older age. There was also no association between carriage of the N allele and development of lethal prostate cancer. Participants whose prostate cancer contained the polymorphic allele were less likely to be overweight or obese (26%) compared to men with the DD genotype (47.8%). This large study observed no overall association between the D104N endostatin polymorphism and prostate cancer risk or prognosis.

Mucci LA, Stark JR, Figg WD, Schumacher F, Li H, Abe M, Hennessy K, Stampfer MJ, Gaziano JM, Ma J, Kantoff PW
Int J Cancer. 2009 Mar 11. (Epub ahead of print)
10.1002/ijc.24423

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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