👤 Sandra Motley

Fish oil supplementation may represent a potential chemopreventive agent for reducing colorectal cancer risk. The mechanism of action of fish oil is unknown but presumed to be related to eicosanoid modification. The purpose of this study was to evaluate the effects of fish oil supplementation on the levels of urinary and rectal eicosanoids. We conducted a randomized, double-blind, controlled trial of 2.5 g of fish oil per day compared with olive oil supplementation over a 6-month period. Study participants had a history of colorectal adenomas. Randomization was stratified based on the gene variant rs174535 in the fatty acid desaturase 1 enzyme (FADS1), which affects tissue levels of arachidonic acid. A total of 141 participants were randomized. Urinary prostaglandin E2 metabolite (PGE-M) was measured at baseline, 3, and 6 months and rectal prostaglandin E2 (PGE2) at baseline and 6 months. Repeated-measures linear regression was used to determine the effect of the intervention on each outcome measure. Overall, fish oil supplementation was found to reduce urinary PGE-M production compared with olive oil (P=0.03). Fish oil did not reduce rectal PGE2 overall; however, it did significantly reduce PGE2 in the subgroup of participants not using aspirin or NSAIDs (P=0.04). FADS1 genotype did not seem to modify effects of fish oil on PGE2 production. We conclude that fish oil supplementation has a modest but beneficial effect on eicosanoids associated with colorectal carcinogenesis, particularly in those not taking aspirin or NSAIDs. Show less

Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samples were genotyped using the Illumina Cardio-MetaboChip platform. Multivariable adjusted linear regression models were used to evaluate SNPs (additive coding) in relation to natural-log transformed (log) PV. We compared SNP-PV results from biopsy-negative men to 442 men with low-grade prostate cancer with similar levels of obesity and PV. Beta-coefficients from the discovery and replication samples were then aggregated with fixed effects inverse variance weighted meta-analysis. SNP rs11736129 (near the pseudo-gene LOC100131429) was significantly associated with log-PV (beta: 0.16, p-value 1.16x10(-8)) after adjusting for multiple testing. Other noteworthy SNPs that were nominally associated (p-value < 1x10(-4)) with log-PV included rs9583484 (intronic SNP in COL4A2), rs10146527 (intronic SNP in NRXN3), rs9909466 (SNP near RPL32P31), and rs2241606 (synonymous SNP in SLC12A7). We found several SNPs in metabolic loci associated with PV. Further studies are needed to confirm our results and elucidate the mechanism between these genetic loci, PV, and clinical BPH. Show less