Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism.

Azrad, Maria

Zhang, Kui

Vollmer, Robin T

Madden, John

Polascik, Thomas J

Snyder, Denise C

Ruffin, Mack T

Moul, Judd W

Brenner, Dean

Hardy, Robert W

Demark-Wahnefried, Wendy

Medeiros, Rui

United States

2016-01-02T03:46:49Z

2012

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.

http://www.ncbi.nlm.nih.gov/pubmed/23285256

PONE-D-12-25045

1932-6203

https://hdl.handle.net/10161/11293

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0053104

Adult

Aged

Carcinoma

Clinical Trials, Phase II as Topic

Dietary Supplements

Fatty Acid Desaturases

Genetic Variation

Humans

Ki-67 Antigen

Male

Metabolic Networks and Pathways

Middle Aged

Multicenter Studies as Topic

Neoplasm Invasiveness

Polymorphism, Single Nucleotide

Prostate

Prostatectomy

Prostatic Neoplasms

Randomized Controlled Trials as Topic

alpha-Linolenic Acid

Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism.

Journal article

Snyder, Denise C|0000-0003-1160-7433

Moul, Judd W|0000-0001-9228-8344

http://www.ncbi.nlm.nih.gov/pubmed/23285256

e53104

12

Anesthesiology

Clinical Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Pathology

School of Medicine

Surgery

Surgery, Urology

Published

7