Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC).
A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform.
No relation to risk was found. Three SNPs were associated with CRPC prognosis in Caucasians: ABCB11 rs7602171G>A (p = 0.003; n = 30; hazard ratio [HR]: 0.307), GSTP1 rs1799811C>T (p = 0.001; n = 38; HR: 0.254) and SLC5A6 rs1395 (p = 0.004; n = 35; HR: 3.15). Two other polymorphisms among Caucasians were associated with interesting trends: ABCB4 rs2302387C>T (p = 0.039) and ABCC5 rs939339A>G (p = 0.018).
This exploratory study is the first to show that polymorphisms in several absorption, distribution, metabolism and elimination genes may be associated with CRPC prognosis.
Pharmacogenomics. 2016 Jan 24 [Epub ahead of print]
Tristan M Sissung, John Deeken, Crystal R Leibrand, Douglas K Price, Sheryl Ehrlich, Seth M Steinberg, David J Liewehr, William Dahut, William D Figg
Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA., Inova Comprehensive Cancer & Research Institute, Falls Church, VA 22042, USA., Molecular Pharmacology Program, National Cancer Institute, 9000 Rockville Pike, Building 10, Room 5A01, Bethesda, MD 20892, USA., Biostatistics & Data Management Section, Office of the Clinical Director, National Cancer Institute, NIH, Shady Grove, MD 20850, USA., Prostate Cancer Clinical Research Section, Genitourinary Malignancies Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.