Levin Albert M, Zuhlke Kimberly A, Ray Anna M, Cooney Kathleen A, Douglas Julie A
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-0618, USA.
Prostate. 2007 Oct 1;67(14):1507-13. doi: 10.1002/pros.20642.
Expression of the alpha-methylacyl-CoA racemase (AMACR) gene has been established as a sensitive and specific biomarker for the diagnosis of prostate cancer. An initial study has also suggested that the risk of familial (but not sporadic) prostate cancer may be associated with germline variation in the AMACR gene.
In a study of brothers discordant for the diagnosis of prostate cancer (including 449 affected and 394 unaffected men) from 332 familial and early-onset prostate cancer families, we used conditional logistic regression and family-based association tests to investigate the association between prostate cancer and five single nucleotide polymorphisms (SNPs) tagging common haplotype variation within the coding and regulatory regions of AMACR.
The strongest evidence for prostate cancer association was for SNP rs3195676, with an estimated odds ratio of 0.58 (95% confidence interval = 0.38-0.90; P = 0.01 for a recessive model). This non-synonymous SNP (nsSNP) results in a methionine-to-valine substitution at codon 9 (M9V) in exon 2 of the AMACR gene. Three additional nsSNPs showed suggestive evidence for prostate cancer association (P < or = 0.10).
Our results confirm an initial report of association between the AMACR gene and the risk of familial prostate cancer. These findings emphasize the value of studying early-onset and familial prostate cancer when attempting to identify genetic variation associated with prostate cancer.
α-甲基酰基辅酶A消旋酶（AMACR）基因的表达已被确立为诊断前列腺癌的一种敏感且特异的生物标志物。一项初步研究还表明，家族性（而非散发性）前列腺癌的风险可能与AMACR基因的种系变异有关。
在一项对来自332个家族性和早发性前列腺癌家族中前列腺癌诊断结果不一致的兄弟（包括449名患病男性和394名未患病男性）的研究中，我们使用条件逻辑回归和基于家族的关联测试，来研究前列腺癌与五个单核苷酸多态性（SNP）之间的关联，这些SNP标记了AMACR编码区和调控区内常见的单倍型变异。
前列腺癌关联的最有力证据是SNP rs3195676，估计优势比为0.58（95%置信区间 = 0.38 - 0.90；隐性模型下P = 0.01）。这个非同义SNP（nsSNP）导致AMACR基因外显子2中第9密码子处的甲硫氨酸替换为缬氨酸（M9V）。另外三个nsSNP显示出前列腺癌关联的提示性证据（P≤0.10）。
我们的结果证实了AMACR基因与家族性前列腺癌风险之间关联的初步报告。这些发现强调了在试图识别与前列腺癌相关的基因变异时，研究早发性和家族性前列腺癌的价值。
