A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer.
OBJECTIVE
To determine if patients with advanced prostate cancer carrying a polymorphism that codes for a more active testosterone transporter have less durable responses to androgen-deprivation therapy (ADT) than patients not carrying this polymorphism.


METHODS
We previously determined that a polymorphism in SLCO1B3 affects testosterone transport and that those men who have at least one wild-type T allele at the 334 T > G polymorphism in this gene have a shorter survival. We hypothesized that the T allele which increases testosterone transport would be associated with a shorter interval from ADT to androgen independence. We examined the association between this SLCO1B3 polymorphism and time from ADT to androgen independence, ADT to prostate-specific antigen (PSA) nadir and PSA nadir to androgen independence in 68 Caucasian patients with advanced prostate cancer who were treated with ADT with metastatic disease (D2) or biochemical failure with no metastatic disease (D0).


RESULTS
When examined separately, patients in the individual stages tended to have a shorter time to androgen independence with the T allele in the D0 (P = 0.11) and D2 (P = 0.18) groups. Combining these groups and stratifying by stage yielded a statistically significant shorter time to androgen independence with the T allele (P = 0.048).


CONCLUSIONS
A polymorphism in a transporter that increases testosterone import is associated with a shorter time to androgen independence in patients with prostate cancer who are treated with ADT.
Clinical Pharmacology Program, National Cancer Institute, Bethesda, MD, USA. nima.sharifi@utsouthwestern.edu
Nima
N
Sharifi
Akinobu
A
Hamada
Tristan
T
Sissung
Romano
R
Danesi
David
D
Venzon
Caitlin
C
Baum
James L
JL
Gulley
Douglas K
DK
Price
William L
WL
Dahut
William D
WD
Figg
D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D013739:Testosterone / Q000378:metabolism*
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D026901:Membrane Transport Proteins; D013739:Testosterone; D017430:Prostate-Specific Antigen