Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
PLoS One. 2012;7(12):e53104. doi: 10.1371/journal.pone.0053104. Epub 2012 Dec 28.
Previous observational studies have reported associations between prostate cancer and alpha-linolenic acid (ALA). However, few investigations have been able to study this relationship prospectively and in well-controlled settings. Moreover, no studies have determined whether single nucleotide polymorphisms (SNPs) that influence ALA metabolism are associated with this common cancer. The purpose of this study was to explore associations between prostatic levels of ALA, SNPs and prostate cancer-specific biomarkers in samples collected from a previous randomized clinical trial conducted using a presurgical model and which tested the effects of flaxseed supplementation, a rich source of ALA, prior to prostatectomy (n = 134). Serum prostate-specific antigen (PSA) was determined and immunohistochemistry was used to assess tumor proliferation rate (Ki67). Prostatic ALA was determined with gas chromatography. Seven previously identified SNPs associated with delta-6 desaturase activity (rs99780, rs174537, rs174545, rs174572, rs498793, rs3834458 and rs968567) were tested for associations with prostatic ALA, PSA and Ki67. Despite consuming seven times more ALA per day, men in the flaxseed arm had similar amounts of prostatic ALA relative to men not consuming flaxseed. In unadjusted analysis, there were significant positive associations between prostatic ALA and PSA (ρ = 0.191, p = 0.028) and Ki67 (ρ = 0.186, p = 0.037). After adjusting for covariates (flaxseed, age, race, BMI and statin-use) the association between ALA and PSA remained (p = 0.004) but was slightly attenuated for Ki67 (p = 0.051). We did not observe associations between any of the SNPs studied and prostatic ALA; however, in models for PSA there was a significant interaction between rs498793 and ALA and for Ki67 there were significant interactions with ALA and rs99780 and rs174545. Independent and inverse associations were observed between rs174572 and Ki67. This study provides evidence that prostatic ALA, independent of the amount of ALA consumed, is positively associated with biomarkers of aggressive prostate cancer and that genetic variation may modify this relationship.
先前的观察性研究报告称，前列腺癌与α-亚麻酸（ALA）之间存在关联。然而，很少有研究能够前瞻性地在严格控制的环境中研究这种关系。此外，尚无研究确定影响 ALA 代谢的单核苷酸多态性（SNP）是否与这种常见癌症有关。本研究旨在探讨先前使用前列腺切除术前模型进行的随机临床试验中收集的样本中前列腺 ALA、SNP 与前列腺癌特异性生物标志物之间的关系，该试验测试了亚麻籽补充剂（富含 ALA）的效果，n=134。测定血清前列腺特异性抗原（PSA），并用免疫组织化学法评估肿瘤增殖率（Ki67）。用气相色谱法测定前列腺 ALA。测试了先前确定的与 δ-6 去饱和酶活性相关的 7 个 SNP（rs99780、rs174537、rs174545、rs174572、rs498793、rs3834458 和 rs968567）与前列腺 ALA、PSA 和 Ki67 的关系。尽管每天摄入的 ALA 是对照组的七倍，但亚麻籽组的男性前列腺中的 ALA 含量与未食用亚麻籽的男性相似。在未调整的分析中，前列腺 ALA 与 PSA（ρ=0.191，p=0.028）和 Ki67（ρ=0.186，p=0.037）之间存在显著正相关。调整协变量（亚麻籽、年龄、种族、BMI 和他汀类药物使用）后，ALA 与 PSA 之间的关联仍然存在（p=0.004），但 Ki67 略有减弱（p=0.051）。我们没有观察到研究的任何 SNP 与前列腺 ALA 之间的关联；然而，在 PSA 的模型中，rs498793 与 ALA 之间存在显著的相互作用，在 Ki67 的模型中，rs99780 和 rs174545 与 ALA 之间存在显著的相互作用。观察到 rs174572 与 Ki67 之间存在独立的负相关关系。本研究提供的证据表明，前列腺 ALA 与侵袭性前列腺癌的生物标志物呈正相关，且独立于 ALA 的摄入量，而遗传变异可能会改变这种关系。
