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Temporal Variation and Identification of Factors Associated with Endogenous Retinoic Acid Isomers in Serum from Brazilian Women

¹ Cancer Prevention and Control Program, University of Arizona Cancer Center and Epidemiology and Biostatistics Division, Mel and Enid Zuckerman Arizona College of Public Health, Tucson, Arizona; ² Craft Technologies, Inc., Wilson, North Carolina; ³ Ludwig Institute for Cancer Research, São Paulo, Brazil; and Departments of ⁴ Oncology and ⁵ Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada

Requests for reprints: Anna R. Giuliano, H. Lee, Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC-2E, Tampa, FL 33612. Phone: 813-903-6820. E-mail: giuliano{at}moffitt.usf.edu

Objective: Retinoids (natural and synthetic derivatives of vitamin A) have cancer chemotherapeutic and chemopreventive activities. Retinoic acid (RA) treatment has been associated with significant regression of preneoplastic lesions. However, serious toxicity associated with some therapies has made long-term chemoprevention in healthy populations unfeasible. Recently, serum RA has been shown to increase in response to oral retinol (vitamin A) supplementation. Here, we assess the variability of circulating RA levels and the lifestyle, demographic, and nutritional factors that explain such variability.

Method: Total RA concentration and the concentrations of RA isomers (all-trans-RA, 13-cis-RA, and 9-cis-RA) were measured by high-pressure liquid chromatography in serum samples obtained 4 months apart from 502 women participating in the Ludwig-McGill Cohort (São Paulo, Brazil).

Results: The relative abundance of the three RA isomers was similar for each visit (baseline and month 4), with 13-cis-RA having the highest concentrations followed by 9-cis-RA and all-trans-RA. The within-person variability of total RA and individual isomers was low. Using multivariate logistic regression models (upper tertile versus low/middle tertile of serum RA), we found that age, race, oral contraceptive use, total number of pregnancies, and season of initial blood draw were significantly associated with at least one endogenous RA isomer level. All endogenous RA isomers were positively associated with serum retinol, ß-carotene, and ß-cryptoxanthin levels.

Conclusion: These results have implications for the design of future epidemiologic studies focused on assessing RA-disease association and intervention studies aimed at modulating RA levels.