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Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy
Author(s) -
Williams Heinric,
Powell Isaac J.,
Land Susan J.,
Sakr Wael A.,
Hughes Mark R.,
Patel Nimesh P.,
Heilbrun Lance K.,
Everson Richard B.
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20103
Subject(s) - prostate cancer , medicine , prostatectomy , oncology , calcitriol receptor , taqi , prostate , vitamin d and neurology , disease , cancer , genotype , endocrinology , polymorphism (computer science) , biology , gene , genetics
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.