title: Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism.
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.
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, United States of America. maria123@uab.edu
authors.forename: Maria
authors.initials: M
authors.lastname: Azrad
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: Robin T
authors.initials: RT
authors.lastname: Vollmer
authors.forename: John
authors.initials: J
authors.lastname: Madden
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Polascik
authors.forename: Denise C
authors.initials: DC
authors.lastname: Snyder
authors.forename: Mack T
authors.initials: MT
authors.lastname: Ruffin
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.forename: Dean
authors.initials: D
authors.lastname: Brenner
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hardy
authors.forename: Wendy
authors.initials: W
authors.lastname: Demark-Wahnefried
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D017322:Clinical Trials, Phase II as Topic; D019587:Dietary Supplements; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000737:chemistry* / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016032:Randomized Controlled Trials as Topic; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D017962:alpha-Linolenic Acid; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human