Is oleic acid or squalene the important preventive agent?

Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy Rutgers, The State University of New Jersey, 41D Gordon Road, Piscataway, NJ 08854-8020

Dear Sir:

van Dam et al (1) reported that analysis of the Health Professionals Follow-up Study found an inverse association between dietary intake of monounsaturated fat and basal cell carcinoma of the skin. Dietary monounsaturated fat is essentially oleic acid and is present in a variety of fats of both plant and animal origin. In laboratory studies in mice, topically applied oleic acid was found to be a potent inhibitor of skin carcinogenesis induced by benzo[a]pyrene (2).

A particularly rich single source of oleic acid is olive oil, which contains 70% oleic acid in the form of glycerides. However, olive oil also contains 0.5–0.7% squalene, representing the major source of dietary squalene. Squalene has also been reported to be a potent inhibitor of benzo[a]pyrene-induced skin carcinogenesis in mice (2). In a later study, Murakoshi et al (3) reported that topically applied squalene markedly suppressed the promoting effect of 12-O-tetradecanoylphorbol-13-acetate on mouse skin tumors initiated with 7,12-dimethylbenz[a]anthracene. Thus, the monounsaturated fat in the results of van Dam et al (1) may be in part a surrogate marker for a dietary association with squalene. This is quite interesting because human sebum contains 12% squalene, and the dry weight of human skin may contain up to 0.1% (4).

Increased dietary intake of oleic acid is known to increase serum and tissue oleic acid concentrations. Similarly, increased serum and tissue concentrations of squalene are reported with increased oral dosing in humans (4) and rats (5). To my knowledge, no data for humans are currently available to indicate whether increased dietary oleic acid or squalene is reflected in increased concentrations in the sebum. Such data would strongly support the interesting inverse association found by van Dam et al (1) and would support further studies of the effectiveness of dietary or topically applied oleic acid or squalene as preventive agents against basal cell carcinoma of the skin.

REFERENCES

1. van Dam RM, Huang Z, Giovannucci E, et al. Diet and basal cell carcinoma of the skin in a prospective cohort of men. Am J Clin Nutr 2000;71:135–41.
2. Van Duuren BL, Goldschmidt BM. Co-carcinogenic and tumor-promoting agents in tobacco carcinogenesis. J Natl Cancer Inst 1976;56:1237–42.
3. Murakoshi M, Nishino H, Tokuda H, et al. Inhibition by squalene of the tumor-promoting activity of 12-O-tetradecanoylphorbol-13-acetate in mouse-skin carcinogenesis. Int J Cancer 1992;52:950–2.
4. Liu CK, Ahrens EH Jr, Schreibman H, Crouse R. Measurement of squalene in human tissues and plasma: validation and application. J Lipid Res 1976;17:38–45.
5. Strandberg E, Tilvis R, Miettinen TA. Variations of hepatic cholesterol precursors during altered flows of endogenous and exogenous squalene in the rat. Biochim Biophys Acta 1989;1001:150–6.