posted on 2016-01-08, 00:00authored byM.E. Wright, D. Albanes, A.B. Moser, S.J. Weinstein, K. Snyder, S. Mannisto, P.H. Gann
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 a-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 AlphaTocopherol,
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
b-carotene concentrations were noted in relation to total and aggressive
disease among participants who did not receive b-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 b-carotene among men not
taking b-carotene supplements should be interpreted cautiously, as they are
likely due to chance.
Funding
Supported by American Cancer Society grant
MSRG-08-109-01-CCE, Department of
Defense grant PC050393, the Intramural
Research Program of the NIH and the
National Cancer Institute, and U.S. Public
Health Service contracts N01-CN-45165,
N01-RC-45035, N01-RC-37004 and
HHSN261201000006C from the National
Cancer Institute, Department of Health and
Human Services.