The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia
The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia
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DOI：
10.1158/1055-9965.epi-04-0778
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Giles, GG
中科院分区：
文献类型：
--
作者：
Hayes, VM;Severi, G;Giles, GG
雄激素受体（AR）基因编码一种转录因子，介导雄激素在靶组织（包括前列腺）中的作用。前列腺癌是雄激素依赖性的，暗示AR在这种男性疾病的易感性。男性型秃发，雄激素性脱发，最近与前列腺癌，表明共享雄激素途径。AR中的CAG和GGC重复序列已被广泛研究作为前列腺癌易感性的标志物，但结果不确定，而AR-E211 G > A多态性与雄激素性脱发相关。在一项澳大利亚人群病例对照研究中，我们评估了重复连锁单核苷酸多态性作为前列腺癌（包括雄激素性脱发）风险关联的标志物。在815例前列腺癌患者和719例对照组中，A等位基因携带者的比例在各组中相同。总体而言，没有证据表明A等位基因与前列腺癌风险之间存在关联，然而，转移性前列腺癌中A等位基因携带者的比例（5%）低于不太晚期的疾病（16%，P = 0.03）。A等位基因携带者的比例在非秃发男性中为24%，但在单纯头顶秃发（13%，P = 0.001）或合并前额秃发（7%，P < 0.0001）的男性中则较低。A等位基因和脱发之间的这种负相关与前列腺癌状态无关（相互作用P = 0.2）。这些结果表明，AR-E211 A等位基因与功能性重复序列连锁，与转移性前列腺癌的较低风险和脱发的较低风险相关。
The androgen receptor (AR) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. Prostate cancer is androgen dependent, implicating AR in susceptibility to this male condition. Male pattern balding, androgenetic alopecia, has recently been associated with prostate cancer, suggesting shared androgen pathways. The CAG and GGC repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G > A polymorphism has been associated with androgenetic alopecia. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in prostate cancer, including androgenetic alopecia, in an Australian population-based case-control study. In 815 prostate cancer cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of prostate cancer, however, the proportion of A-allele carriers in metastatic prostate cancer (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex alopecia alone (13%, P = 0.001) or in combination with frontal alopecia (7%, P < 0.0001). This inverse association between the A allele and baldness was independent of prostate cancer status (P for interaction = 0.2). These results suggest that the AR-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of metastatic prostate cancer and a lower risk of alopecia.