Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy

Autor: Nimesh P. Patel, Isaac J. Powell, Richard B. Everson, Wael Sakr, Heinric Williams, Mark R. Hughes, Susan Land, Lance K. Heilbrun
Rok vydání: 2004
Předmět:
Zdroj: The Prostate. 61:267-275
ISSN: 1097-0045
0270-4137
DOI: 10.1002/pros.20103
Popis: BACKGROUND Vitamin D has been linked with prostate cancer risk in epidemiologic studies and has antiproliferative, prodifferentiation, and antimetastatic properties in experimental systems. Its hormonal activity is mediated by the vitamin D receptor. We investigated whether germ-line genetic variation in the vitamin D receptor impacts progression of prostate cancer after radical prostatectomy. METHODS We analyzed BsmI and TaqI polymorphisms using archived specimens from a large series of radical prostatectomy patients at a single institution. Our series included 428 white men (WM) and 310 African–American men (AAM) who were carefully and uniformly staged and followed for 5–10 years. RESULTS The distribution of polymorphisms varied between WM and AAM. There was little association between genotype and extent of disease at diagnosis, Gleason score, preoperative PSA, or recurrence overall. Among WM with locally advanced disease, however, the BsmI B allele protected against recurrence in models examining gene dose (P = 0.04) and dominant effects (P = 0.05). CONCLUSIONS Overall vitamin D receptor polymorphisms did not predict pathologic features of prostate cancer but may impact on risk of recurrence among men in certain risk groups. Analysis of polymorphisms may provide clues about the mechanisms through which vitamin D exerts its inhibitory effects on prostate cancer in vivo in men. © 2004 Wiley-Liss, Inc.
Databáze: OpenAIRE
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