Abstract A95: Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: A relationship which may depend on genetic variation in ALA metabolism
Authors: Azrad Maria , Hardy Robert W. , Demark-Wahnefried Wendy , Zhang Kui , Vollmer Robin T. , Madden John , Polascik Thomas , Snyder Denise C. , Ruffin Mack T. , Moul Judd , Brenner Dean 
Published: January 2014

Abstract
Previous observational studies have reported associations between prostate cancer and alpha-linolenic acid (ALA), the most commonly consumed omega-3 polyunsaturated fatty acid in a Western diet. However, few investigations have been able to study this relationship prospectively and in well-controlled settings. Moreover, to date, 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 30 g/d of flaxseed, a rich source of ALA, for ∼30 days prior to prostatectomy (n=134). Serum prostate-specific antigen (PSA) was determined and immunohistochemistry was used to assess tumor Ki67 staining (proliferation rate). Prostatic ALA was determined with gas chromatography. Seven previously identified SNPs (rs99780, rs174537, rs174545, rs174572, rs498793, rs3834458 and rs968567) were tested for associations with prostatic ALA, PSA and Ki67. Despite consuming nearly seven times more ALA per day, men in the flaxseed arm had similar amounts of prostatic ALA relative to men not consuming flaxseed [median (range) 0 (0-9.41) versus 0 (0-0.85), p=0.296. 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 (p=0.017) and for Ki67 there were significant interactions with ALA and rs99780 (p=0.033) and rs174545 (p=0.047). An independent association between rs174572 and Ki67 was observed (p=0.007). This study provides evidence that prostatic ALA, independent of the amount of ALA consumed, is positively associated with biomarkers of aggressive prostate cancer. This study also observed for the first time that SNPs related to ALA metabolism may modify the association between ALA and prostate cancer.
Citation Format: Maria Azrad, Robert W. Hardy, Wendy Demark-Wahnefried, Kui Zhang, Robin T. Vollmer, John Madden, Thomas Polascik, Denise C. Snyder, Mack T. Ruffin, Judd Moul, Dean Brenner. Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: A relationship which may depend on genetic variation in ALA metabolism. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A95.