Racial differences in CYP3A4 genotype and survival among men treated on Radiation Therapy Oncology Group (RTOG) 9202: a phase III randomized trial.
OBJECTIVE
Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4 *1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02.


METHODS
From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) +/- 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression using American Society for Therapeutic Radiology and Oncology consensus guidelines.


RESULTS
There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression.


CONCLUSIONS
The samples analyzed support previously reported observations about the distribution of CYP3A4 *1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.
Roach
Mack
M
Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. mroach@radonc.ucsf.edu
De Silvio
Michelle
M
Rebbick
Timothy
T
Grignon
David
D
Rotman
Marvin
M
Wolkov
Harvey
H
Fisher
Barbara
B
Hanks
Gerald
G
Shipley
William U
WU
Pollack
Alan
A
Sandler
Howard
H
Watkins-Bruner
Deborah
D
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D044383:Black People; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D018450:Disease Progression; D005485:Flutamide / Q000627:therapeutic use; D005838:Genotype; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D017410:Practice Guidelines as Topic; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000208:ethnology* / Q000401:mortality* / Q000532:radiotherapy; D012044:Regression Analysis; D013534:Survival; D044465:White People; D001741:Black or African American
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D017273:Goserelin; D005485:Flutamide; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017430:Prostate-Specific Antigen