Fatty Acid Composition of Red Blood Cell Membranes and Risk of Squamous Cell Carcinoma of the Skin

Abstract

Differential effects of fatty acids on carcinogenesis suggest that fatty acid composition is important in tumor development. Arachidonic acid and its metabolites elicit inflammation and promote tumor formation in mouse skin. Inhibitors of the arachidonic cascade inhibit tumor incidence. A population-based case control study in Southeastern Arizona tested the hypothesis that lower levels of arachidonic acid in RBC membranes were associated with decreased risk of skin squamous cell carcinoma (SCC; n = 335 SCC cases and 321 controls). Extracted and esterified RBC fatty acids were analyzed using capillary gas chromatography. Individual peaks for 14 fatty acids were measured as a percentage of total fatty acids. Logistic regression was used to estimate odds ratios (OR), adjusting for SCC risk factors (age, gender, actinic keratosis history, freckling, and tanning ability). Increased levels of arachidonic acid in RBC membranes were associated with increased risk of SCC [odds ratio (OR), 1.08 per mg/100 mL change; 95% confidence interval (95% CI), 1.02-1.15] and this association remained when controls with actinic keratosis precursor lesions were excluded. SCC risk was highest among the upper quartile of arachidonic acid (OR, 2.38; 95% CI, 1.37-4.12). In contrast, increasing proportions of palmitic acid (OR, 0.94; 95% CI, 0.89-1.00) and palmitoleicacid (OR, 0.49; 95% CI, 0.30-0.81) were associated with reduced SCC risk. More studies are needed to elucidate the function of RBC fatty acids so that recommendations can be made to alter the human diet for cancer prevention. (Cancer Epidemiol Biomarkers Prev 2005;14(4):906 -12)

Plasma Omega-3 and Omega-6 Concentrations and Risk of Cutaneous Basal and Squamous Cell Carcinomas in Australian Adults

“…Although our findings did not show a clear doseresponse relationship, collectively the evidence suggests that moderate omega-3 intake may sustain circulating and target tissue levels to influence early stages of photocarcinogenesis. With respect to omega-6 PUFA, our study failed to confirm earlier findings that higher serum arachidonic acid levels increase SCC risk (11).…”

“…An Arizona-based case-control study showed an inverse association of omega-3 intake and odds of SCC (10), and an increased SCC risk with higher serum levels of arachidonic acid (11). We have also previously reported a marginal increase in SCC risk with greater arachidonic acid intake and a decrease in BCC risk with increasing total omega-6 intake (12).…”

Serum Omega-3 and Omega-6 Fatty Acids and Cutaneous p53 Expression in an Australian Population

“…A large, prospective study in male U.S. health professionals suggested a small but statistically significant positive association between intake of long-chain n-3 fatty acids and risk of basal cell carcinoma, but personal-level past UV exposure could not be accounted for in that study (25). Erythrocyte longchain n-3 fatty acids were not associated with squamous cell carcinoma risk in a case-control study in Arizona, but concentrations of the n-6 fatty acid AA were associated with increased squamous cell carcinoma risk in that study (12). More evidence from studies that are designed to assess specific intake of long-chain fatty acids or biomarkers of these and skin cancer risk is needed.…”

“…On the basis of the literature, we had hypothesized that higher concentrations of n-6 fatty acids would be associated with increased p53 immunoreactivity, because p53 immunoreactivity is an early marker of UV-induced carcinogenesis and n-6 fatty acids have been associated with increased tumor growth (10,11) and increased risk of squamous cell carcinoma of the skin (12). However, our results did not suggest such an association; on the contrary they showed that p53 immunoreactivity was lowest in participants with highest total serum n-6 fatty acid concentrations, although the group differences were of borderline statistical significance (P ¼ 0.08).…”

“…Feeding studies in rodents have shown that diets containing high levels of n-6 fatty acids enhance UV-induced cancer occurrence (10), and upregulate growth of other tumor types (11). In a case-control study, higher erythrocyte arachidonic acid concentrations increased the risk of cutaneous squamous cell carcinoma (12). In light of these opposing effects of n-3 and n-6 fatty acids on skin carcinogenesis, it may be their relative ratio that influences skin cancer development (7).…”