Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism.
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2012
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Abstract
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.
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Azrad, Maria, Kui Zhang, Robin T Vollmer, John Madden, Thomas J Polascik, Denise C Snyder, Mack T Ruffin, Judd W Moul, et al. (2012). Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism. PLoS One, 7(12). p. e53104. 10.1371/journal.pone.0053104 Retrieved from https://hdl.handle.net/10161/11293.
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Scholars@Duke
John Francis Madden
Thomas James Polascik
Prostate cancer imaging
Focal therapy of prostate cancer
Prostate cancer outcomes
Kidney cancer outcomes
Minimally invasive surgery
Nerve sparing cryotherapy
Robotic surgery
Denise Snyder
Facilitating clinical research support and collaborations for Duke faculty, staff, students and trainees. Revitalizing the clinical research professional workforce through innovative initiatives to improve support for clinical research that changes clinical care.
Judd Wendell Moul
Dr Judd Moul joined the Duke faculty in mid 2004 after a career in the US Army Medical Corps mainly at Walter Reed Army Medical Center. He is a retired colonel and a noted researcher and clinician in the area of prostate cancer and is a urologic oncologist. He served as the division chief of Duke Division of Urology from 2004 to 2011 and was named the James H Semans MD Professor of surgery in 2009 becoming Duke's first named endowed chair for urology. He was awarded the Gold Cystoscope Award from the American Urologic Association as well as Castle Connelly Physician of the year for Clinical Medicine in 2009. He has performed more than 1300 radical prostatectomies since joining the Duke faculty and is committed to outcomes research on this series and in other areas of prostate cancer. He served as the Editor for Prostate Cancer and Prostatic Dissease, a Nature Medicine journal, for more than a decade and is a popular speaker and lecturer having been visiting professor and keynote speaker throughout the US and the World. He is very committed to training residents and mentoring students and trainees.
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