Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial

Mack Roach, Michelle De Silvio, Timothy Rebbick, David Grignon, Marvin Rotman, Harvey Wolkov, Barbara Fisher, Gerald Hanks, William U. Shipley, Alan Pollack, Howard Sandler, Deborah Watkins-Bruner

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume69
Issue number1
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP3A
Radiation Oncology
radiation therapy
Radiotherapy
Genotype
Survival
Goserelin
progressions
African Americans
deprivation
polymorphism
Flutamide
Selection Bias
examination
cancer
Androgens
Prostatic Neoplasms
radiation
Guidelines
Radiation

Keywords

  • Genetic polymorphisms
  • Prostate cancer
  • Race
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202 : A Phase III Randomized Trial. / Roach, Mack; De Silvio, Michelle; Rebbick, Timothy; Grignon, David; Rotman, Marvin; Wolkov, Harvey; Fisher, Barbara; Hanks, Gerald; Shipley, William U.; Pollack, Alan; Sandler, Howard; Watkins-Bruner, Deborah.

In: International Journal of Radiation Oncology Biology Physics, Vol. 69, No. 1, 01.09.2007, p. 79-87.

Research output: Contribution to journalArticle

Roach, M, De Silvio, M, Rebbick, T, Grignon, D, Rotman, M, Wolkov, H, Fisher, B, Hanks, G, Shipley, WU, Pollack, A, Sandler, H & Watkins-Bruner, D 2007, 'Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202: A Phase III Randomized Trial', International Journal of Radiation Oncology Biology Physics, vol. 69, no. 1, pp. 79-87. https://doi.org/10.1016/j.ijrobp.2007.03.008
Roach, Mack ; De Silvio, Michelle ; Rebbick, Timothy ; Grignon, David ; Rotman, Marvin ; Wolkov, Harvey ; Fisher, Barbara ; Hanks, Gerald ; Shipley, William U. ; Pollack, Alan ; Sandler, Howard ; Watkins-Bruner, Deborah. / Racial Differences in CYP3A4 Genotype and Survival Among Men Treated on Radiation Therapy Oncology Group (RTOG) 9202 : A Phase III Randomized Trial. In: International Journal of Radiation Oncology Biology Physics. 2007 ; Vol. 69, No. 1. pp. 79-87.
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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.",
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