Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy.
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.
Williams
Heinric
H
The Barbara Ann Karmanos Cancer Institute and Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.
Powell
Isaac J
IJ
Land
Susan J
SJ
Sakr
Wael A
WA
Hughes
Mark R
MR
Patel
Nimesh P
NP
Heilbrun
Lance K
LK
Everson
Richard B
RB
D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D018167:Receptors, Calcitriol / Q000235:genetics*; D016019:Survival Analysis; D044465:White People / Q000706:statistics & numerical data
D018167:Receptors, Calcitriol