维生素D受体（VDR）和5α-还原酶2（SRD5A2）基因多态性共同作用，会增加非西班牙裔白人和西班牙裔白人患前列腺癌的风险。

VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men.

作者信息

Torkko Kathleen C, van Bokhoven Adrie, Mai Phoung, Beuten Joke, Balic Ivana, Byers Tim E, Hokanson John E, Norris Jill M, Barón Anna E, Lucia M Scott, Thompson Ian M, Leach Robin J

机构信息

Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, USA.

出版信息

Clin Cancer Res. 2008 May 15;14(10):3223-9. doi: 10.1158/1078-0432.CCR-07-4894.

DOI:10.1158/1078-0432.CCR-07-4894

PMID:18483391

Abstract

PURPOSE

Vitamin D and dihydrotestosterone pathways interact to promote the growth of prostatic tissue. The nuclear vitamin D receptor (VDR) moderates the actions of vitamin D. 5alpha-Reductase type II (SRD5A2) codes for the enzyme that converts testosterone to dihydrotestosterone in the prostate. This study tested the interactions of VDR (CDX2, FokI) and SRD5A2 (V89L, A49T) polymorphisms, and their associations with prostate cancer.

EXPERIMENTAL DESIGN

This genetic association study included 932 non-Hispanic White (NHW) men and 414 Hispanic White (HW) men from South Texas. Cases had biopsy-confirmed cancer; controls had normal digital rectal exams and serum prostate-specific antigen levels of <2.5 ng/mL.

RESULTS

Using logistic regression analyses to test associations with prostate cancer, only the V89L polymorphism (VV genotype compared with LL/LV) in HW men was statistically significant [odds ratios (OR), 0.64; 95% confidence intervals (95% CI), 0.41-0.99]. The interaction terms for FokI and V89L in NHW men and CDX2 and V89L in HW men in the logistic model were significant (P = 0.02 and 0.03, respectively). When stratified by V89L genotype, the FokI polymorphism (TT/TC versus CC) was significantly associated with prostate cancer in NHW men with the V89L VV genotype (FokI OR, 1.53; 95% CI, 1.06-2.23). The CDX2 polymorphism (GG versus AG/AA) was significantly associated with prostate cancer only in HW men with the V89L VV genotype (CDX2 OR, 3.16; 95% CI, 1.39-7.19; interaction term P = 0.02).

CONCLUSION

Our results indicate that the SRD5A2 V89L VV genotype interacts with VDR FokI TT/CT genotypes in NHW men and VDR CDX2 GG genotypes in HW men to increase the risk for prostate cancer.

摘要

目的

维生素D和双氢睾酮途径相互作用以促进前列腺组织生长。核维生素D受体（VDR）调节维生素D的作用。II型5α-还原酶（SRD5A2）编码在前列腺中将睾酮转化为双氢睾酮的酶。本研究检测了VDR（CDX2、FokI）和SRD5A2（V89L、A49T）基因多态性的相互作用及其与前列腺癌的关联。

实验设计

这项基因关联研究纳入了来自南德克萨斯州的932名非西班牙裔白人（NHW）男性和414名西班牙裔白人（HW）男性。病例经活检确诊为癌症；对照者直肠指检正常且血清前列腺特异性抗原水平<2.5 ng/mL。

结果

使用逻辑回归分析检测与前列腺癌的关联，仅HW男性中的V89L基因多态性（VV基因型与LL/LV相比）具有统计学意义[比值比（OR），0.64；95%置信区间（95%CI），0.41 - 0.99]。逻辑模型中NHW男性的FokI和V89L以及HW男性的CDX2和V89L的相互作用项具有显著性（P分别为0.02和0.03）。按V89L基因型分层时，FokI基因多态性（TT/TC与CC相比）在具有V89L VV基因型的NHW男性中与前列腺癌显著相关（FokI OR，1.53；95%CI，1.06 - 2.23）。CDX2基因多态性（GG与AG/AA相比）仅在具有V89L VV基因型的HW男性中与前列腺癌显著相关（CDX2 OR，3.16；95%CI，1.39 - 7.19；相互作用项P = 0.02）。