Abstract
Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of α-Methyl-CoA-Racemase (AMACR)—an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97–2.68), 1.12 (0.66–1.90), and 1.14 (0.67–1.94), Ptrend = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating β-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive β-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and pristanic acid levels and prostate cancer risk. Findings indicating that the direction and magnitude of these associations depended upon serum levels of the antioxidant β-carotene among men not taking β-carotene supplements should be interpreted cautiously, as they are likely due to chance.
Highlights
Increased consumption of dairy products and red meat have been linked with higher risks of prostate cancer— aggressive disease—in many epidemiological studies [1,2,3,4,5,6]
Phytanic acid is metabolized to pristanic acid during peroxisomal a-oxidation; pristanic acid is the direct substrate of a-Methyl-CoA-Racemase (AMACR), one of the enzymes that are crucial for proper degradation of phytanic acid
Excessive intake of branched-chain fatty acids that are metabolized by AMACR could provide an explanation for previously reported associations between dairy and red meat intake and prostate cancer risk
Summary
Increased consumption of dairy products and red meat have been linked with higher risks of prostate cancer— aggressive disease—in many epidemiological studies [1,2,3,4,5,6]. Polymorphisms in the AMACR gene have been linked with elevated risks of prostate cancer in several independent studies [13,14,15,16]. These findings highlight the potential importance of phytanic and pristanic acids—either directly or through their interaction with AMACR—in prostate carcinogenesis. The exact mechanism (s) remain unclear, it is possible that excessive levels of phytanic or pristanic acids could lead to overexpression of AMACR or to increased generation of reactive oxygen species-known byproducts of phytanic acid metabolism [17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
