Sissung Tristan M, Deeken John, Leibrand Crystal R, Price Douglas K, Ehrlich Sheryl, Steinberg Seth M, Liewehr David J, Dahut William, Figg William D
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.
Pharmacogenomics. 2016 Dec;17(18):1979-1986. doi: 10.2217/pgs-2016-0134. Epub 2016 Nov 24.
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).
MATERIALS & METHODS: 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.
代谢和转运在终身暴露于内源性和外源性致癌物的过程中起着主要作用。因此，我们探讨了吸收、分布、代谢和消除基因多态性与去势抵抗性前列腺癌（CRPC）风险及预后之间的关联。
使用Affymetrix DMETv1.0平台对74例患者的634种基因型进行检测。
未发现与风险有关联。在白种人中，有三个单核苷酸多态性（SNP）与CRPC预后相关：ABCB11基因rs7602171G>A（p = 0.003；n = 30；风险比[HR]：0.307）、GSTP1基因rs1799811C>T（p = 0.001；n = 38；HR：0.254）和SLC5A6基因rs1395（p = 0.004；n = 35；HR：3.15）。在白种人中，另外两个多态性呈现出有趣的趋势：ABCB4基因rs2302387C>T（p = 0.039）和ABCC5基因rs939339A>G（p = 0.018）。
这项探索性研究首次表明，几种吸收、分布、代谢和消除基因的多态性可能与CRPC预后相关。
