Racial differences in CYP3A4 genotype and survival among men treated on Radiation Therapy Oncology Group (RTOG) 9202: a phase III randomized trial

Int J Radiat Oncol Biol Phys. 2007 Sep 1;69(1):79-87. doi: 10.1016/j.ijrobp.2007.03.008. Epub 2007 May 10.

Abstract

Purpose: 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 and materials: 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.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Black People
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • Disease Progression
  • Flutamide / therapeutic use
  • Genotype*
  • Goserelin / therapeutic use
  • Humans
  • Male
  • Neoplasm Proteins / genetics*
  • Practice Guidelines as Topic
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / ethnology*
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / radiotherapy
  • Regression Analysis
  • Survival
  • White People

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Neoplasm Proteins
  • Goserelin
  • Flutamide
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Prostate-Specific Antigen