Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Prostate. 2011 Apr;71(5):498-506. doi: 10.1002/pros.21267. Epub 2010 Oct 13.
Alpha-methylacyl CoA racemase (AMACR) is an enzyme involved in fatty acids metabolism. One of AMACRs primary substrates, phytanic acid, is principally obtained from dietary red meat/dairy, which are associated with prostate cancer (PCa) risk. AMACR is also a tumor tissue biomarker over-expressed in PCa. In this study, we explored the potential relationship between AMACR polymorphisms, red meat/dairy intake, and PCa risk.
Caucasian participants from two population-based PCa case-control studies were included. AMACR single nucleotide polymorphisms (SNPs) were selected to capture variation across the gene and regulatory regions. Red meat and dairy intake was determined from food frequency questionnaires. The odds ratio (OR) of PCa (overall and by disease aggressiveness) was estimated by logistic and polytomous regression. Potential interactions between genotypes and dietary exposures were evaluated.
Data from 1,309 cases and 1,267 controls were analyzed. Carriers of the variant T allele (rs2287939) had an OR of 0.81 (95% CI 0.68-0.97) for less aggressive PCa, but no alteration in risk for more aggressive PCa. Red meat consumption was positively associated with PCa risk, and the association was stronger for more aggressive disease (lowest vs. highest tertile OR=1.55, 95% CI 1.10-2.20). No effect modification of AMACR polymorphisms by either dietary red meat or dairy intake on PCa risk was observed.
PCa risk varied by level of red meat intake and by one AMACR SNP, but there was no evidence for gene-environment interaction. These findings suggest that the effects of AMACR polymorphisms and red meat and dairy on PCa risk are independent.
α-甲基酰基辅酶 A 消旋酶（AMACR）是参与脂肪酸代谢的一种酶。AMACR 的主要底物之一植烷酸主要从饮食中的红肉/乳制品中获得，而红肉/乳制品与前列腺癌（PCa）的风险有关。AMACR 也是 PCa 组织中过度表达的肿瘤组织生物标志物。在这项研究中，我们探讨了 AMACR 多态性、红肉/乳制品摄入与 PCa 风险之间的潜在关系。
纳入了两项基于人群的 PCa 病例对照研究的白种人参与者。选择 AMACR 单核苷酸多态性（SNP）来捕获基因和调控区域的变异。红肉和乳制品的摄入量通过食物频率问卷确定。通过逻辑回归和多项回归估计 PCa（整体和疾病侵袭性）的比值比（OR）。评估基因型与饮食暴露之间的潜在相互作用。
分析了 1309 例病例和 1267 例对照的数据。携带变异 T 等位基因（rs2287939）的个体患侵袭性较低的 PCa 的 OR 为 0.81（95%CI 0.68-0.97），但侵袭性较高的 PCa 风险无改变。红肉消费与 PCa 风险呈正相关，且与侵袭性更强的疾病相关性更强（最低与最高三分位 OR=1.55，95%CI 1.10-2.20）。未观察到 AMACR 多态性与饮食中的红肉或乳制品摄入对 PCa 风险的相互作用。
PCa 风险因红肉摄入量的不同而有所不同，且与 AMACR 中的一个 SNP 有关，但没有基因-环境相互作用的证据。这些发现表明，AMACR 多态性与红肉和乳制品对 PCa 风险的影响是独立的。
