SRD5A2和CYP3A4基因座上前列腺癌易感性等位基因频率的种族差异。

Ethnic differences in the frequency of prostate cancer susceptibility alleles at SRD5A2 and CYP3A4.

作者信息

Zeigler-Johnson C M, Walker A H, Mancke B, Spangler E, Jalloh M, McBride S, Deitz A, Malkowicz S B, Ofori-Adjei D, Gueye S M, Rebbeck T R

机构信息

University of Pennsylvania, Philadelphia, Pa, USA.

出版信息

Hum Hered. 2002;54(1):13-21. doi: 10.1159/000066695.

DOI:10.1159/000066695

PMID:12446983

Abstract

OBJECTIVES

Ethnic differences in prostate cancer incidence are well documented, with African-Americans having among the highest rates in the world. Ethnic differences in genotypes for genes associated with androgen metabolism including SRD5A2 and CYP3A4 also may exist. The aim of this study was to evaluate differences in these genotypes by ethnicity.

METHODS

We studied cancer-free controls representative of four groups: 147 African Americans, 410 Caucasian-Americans, 129 Ghanaians, and 178 Senegalese. PCR-based genotype analysis was undertaken to identify two alleles (V89L, A49T) at SRD5A2 and *1B allele at CYP3A4.

RESULTS

Differences were observed for V89L (variant frequency of 30% in Caucasians, 27% in African Americans, 19% in Ghanaians, and 18% in Senegalese, p = 0.002) and were observed for CYP3A4*1B (variant frequencies of 8% in Caucasians, 59% in African Americans, 81% in Ghanaians, and 78% in Senegalese, p = 0.0001). Pooled data combining the present data and previously published data from from Asian, Hispanic, and Arab cancer-free controls showed significant ethnic differences for SRD5A2 and CYP3A4 polymorphisms. Overall, Asians were least likely to have alleles associated with increased prostate cancer risk, while Africans were most likely to have those alleles.

CONCLUSIONS

These results suggest that ethnicity-specific differences in genotype frequencies exist for SRD5A2 and CYP3A4. Africans and African-Americans have the highest frequency of those alleles that have previously been associated with increased prostate cancer risk. Future studies should address whether allele frequency differences in part explain differences in prostate cancer incidence in these populations.

摘要

目的

前列腺癌发病率的种族差异已有充分记录，非裔美国人的发病率位居世界前列。与雄激素代谢相关的基因（包括SRD5A2和CYP3A4）的基因型也可能存在种族差异。本研究的目的是评估这些基因型在不同种族间的差异。

方法

我们研究了代表四组的无癌对照人群：147名非裔美国人、410名美国白人、129名加纳人和178名塞内加尔人。采用基于聚合酶链反应（PCR）的基因型分析来鉴定SRD5A2基因的两个等位基因（V89L、A49T）以及CYP3A4基因的*1B等位基因。

结果

观察到V89L存在差异（白人的变异频率为30%，非裔美国人为27%，加纳人为19%，塞内加尔人为18%，p = 0.002），CYP3A4*1B也存在差异（白人的变异频率为8%，非裔美国人为59%，加纳人为81%，塞内加尔人为78%，p = 0.0001）。将本研究数据与先前发表的来自亚洲、西班牙裔和阿拉伯无癌对照人群的数据合并后的汇总数据显示，SRD5A2和CYP3A4基因多态性存在显著的种族差异。总体而言，亚洲人携带与前列腺癌风险增加相关等位基因的可能性最小，而非洲人携带这些等位基因的可能性最大。