MP70-18 THE ROLE OF POLYUNSATURATED FATTY ACID METABOLISM ON PROSTATE CANCER AGGRESSIVENESS: AN ANALYSIS OF THE NORTH CAROLINA-LOUISIANA PROSTATE CANCER PROJECT (PCAP)
INTRODUCTION AND OBJECTIVES
Prostate cancer (PCa) incidence is higher in African Americans (AA) compared to European Americans (EA) and higher in Western countries. The recent dramatic increase in the polyunsaturated fatty acid (PUFA) linoleic acid (LA) in the modern Western diet may influence PCa risk; LA is converted to arachidonic acid (ARA), which is further metabolized into pro-inflammatory and tumorigenic mediators. Common genetic variants in desaturase genes (FADS1 and FADS2) alter intrinsic conversion of LA to ARA, with the single nucleotide polymorphism rs174537 G allele most strongly associated with high efficiency conversion. Approximately 80% of AA, compared to ˜45% of EA, are GG at rs174537. We sought to determine the impact of rs174537 in AA and EA on PUFA metabolism and PCa aggressiveness.
METHODS
A subset of PCaP (N=319, 138 AA, 181 EA), a bi-racial population of men with PCa, was genotyped at rs174537. PUFAs were quantitated from plasma samples via FAME using GC/FID. PCa tissue was histologically scored by pathologists. Linear, logistic and Cox proportional hazards models, stratified by ethnicity and adjusted for age and admixture, were used to test associations between rs174537, PUFAs, and PCa aggressiveness.
RESULTS
AA had higher ARA/dihomo-γ-linolenic acid (DGLA) ratio (a surrogate for FADS1 activity) compared to EA (p<0.05). GG genotype at rs174537 is associated with higher ARA/DGLA in EA (p<0.001) and, although in the same direction, not significantly in AA (p=0.30). Higher ARA/DGLA ratio was associated with Gleason ≥8 PCa (OR: 1.32 [1.03, 1.70], p=0.03) in AA but not EA (OR: 0.91 [0.64-1.29], p=0.61). ARA/DGLA ratio is not associated with growth, proliferation rates, or aggressiveness in either ethnicity (p>0.05).
CONCLUSIONS
FADS cluster variants have been shown to be associated with the efficiency by which
dietary LA is converted to ARA and its bioactive metabolites. This pilot study of
PCaP suggests that surrogate biomarkers (ARA/DGLA ratio) of ARA biosynthesis are associated
with PCa aggressiveness in AA but not EA. Larger studies are needed to determine if
FADS variants associated with PUFA levels and ratios, such as rs174537, may contribute
to PCa aggressiveness.
