Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial.
Finasteride concentrations and prostate cancer risk: results from the Prostate Cancer Prevention Trial.
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DOI：
10.1371/journal.pone.0126672
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Figg WD
中科院分区：
文献类型：
--
作者：
Chau CH;Price DK;Till C;Goodman PJ;Chen X;Leach RJ;Johnson-Pais TL;Hsing AW;Hoque A;Tangen CM;Chu L;Parnes HL;Schenk JM;Reichardt JK;Thompson IM;Figg WD
在前列腺癌预防试验（PCPT）中，非那雄胺降低了25%的前列腺癌风险，尽管在非那雄胺组中高级别前列腺癌更为常见。然而，非那雄胺浓度是否会影响前列腺癌风险仍有待确定。在这项研究中，我们检查了PCPT治疗组的血清非那雄胺浓度与前列腺癌风险之间的关系，并确定了影响药物浓度的因素。本巢式病例对照研究的数据来自PCPT。病例来自活检证实的前列腺癌患者和匹配的对照组。采用液相色谱-质谱验证法测定非那雄胺浓度。通过logistic回归确定血清非那雄胺浓度与前列腺癌风险的关系。我们还研究了非那雄胺酶靶基因和代谢基因的多态性是否与药物浓度有关。在检测到非那雄胺浓度的男性中，当非那雄胺浓度作为一个连续变量或按截断点分类时，非那雄胺浓度与前列腺癌风险之间没有关联，无论是低级别还是高级别。由于非那雄胺对前列腺癌没有浓度依赖性的影响，任何摄入非那雄胺的暴露都可能降低前列腺癌的风险。在酶靶和代谢途径中评估的27个snp中，CYP3A4 （rs2242480; rs4646437; rs4986910）和CYP3A5 （rs15524; rs776746）两个基因中的5个snp与非那雄胺浓度的改变显著相关。这些结果表明，非那雄胺暴露可能降低前列腺癌风险，非那雄胺浓度受负责改变其代谢途径的基因的遗传变异的影响。ClinicalTrials.gov NCT00288106
In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations. Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression. Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway. ClinicalTrials.gov NCT00288106
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影响因子：
30.8
作者：
Kuehl, P;Zhang, J;Schuetz, E
通讯作者：
Schuetz, E
DOI：
10.1073/pnas.87.10.3640
发表时间：
1990-05-01
影响因子：
11.1
作者：
ANDERSSON, S;RUSSELL, DW
通讯作者：
RUSSELL, DW
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
158.5
作者：
Thompson, IM;Goodman, PJ;Coltman, CA
通讯作者：
Coltman, CA
影响因子：
6.2
作者：
Gong Z;Kristal AR;Schenk JM;Tangen CM;Goodman PJ;Thompson IM
通讯作者：
Thompson IM