Abstract
Laboratory-based evidence suggests that omega-3 and omega-6 polyunsaturated fatty acids may affect skin photocarcinogenesis, but epidemiologic evidence is inconsistent. In 1,191 White Australian adults, we prospectively investigated associations between baseline plasma concentrations of omega-3 and omega-6 fatty acids and cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). Relative risks (RR) and 95% confidence intervals (CI) were estimated on the basis of number of histologically confirmed tumors diagnosed during follow-up (1997-2007). Plasma eicosapentaenoic acid (EPA) concentrations and omega-3/-6 ratio showed significant inverse associations with SCC tumors, comparing higher tertiles with the lowest, in age- and sex-adjusted models (Ptrend = 0.02 and 0.03, respectively) which weakened after adjustment for past sun exposure. Associations between EPA and SCC were stronger among participants with a history of skin cancer at baseline (n = 378; highest vs. lowest tertile: RR = 0.50; 95% CI, 0.28-0.92; Ptrend = 0.01). Total omega-6 was inversely associated with BCC tumors in multivariate models (P = 0.04; highest vs. lowest tertile: RR = 0.71; 95% CI, 0.51-0.99), and more strongly in the subgroup with past skin cancer. Linoleic and linolenic acids were also inversely associated with BCC occurrence in this subgroup. When fatty acids were analyzed as continuous variables, however, there was no evidence of any linear or nonlinear associations. This study provides some support for reduced skin cancer risk with high plasma concentrations of omega-3 and omega-6 fatty acids, but results depended on how fatty acid data were modeled. Further investigation of these associations in larger datasets is needed.
Highlights
Most keratinocytic skin cancers, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are attributable to solar ultraviolet radiation (UVR) exposure [1, 2]
Among participants with a history of skin cancer, eicosapentaenoic acid (EPA) was more strongly associated with reduced occurrence of SCC tumors after full confounder adjustment (Table 1), but based on the point estimates of EPA tertiles, there was no clear dose–response relationship
Person-based analyses showed similar patterns to the tumor-based analyses, though risk estimates and trends were generally not statistically significant. In this prospective study of associations between plasma phospolipid polyunsaturated fatty acids (PUFA) and keratinocytic skin cancer risk, there was a reduction in risk of SCC tumors in persons with relatively high EPA concentrations and omega-3/-6 ratio, and a decrease in BCC tumor risk with greater total omega-6, linoleic acid, and linolenic acid concentrations
Summary
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are attributable to solar ultraviolet radiation (UVR) exposure [1, 2]. UVR-induced carcinogenesis (photocarcinogenesis) occurs by initiation and promotion of skin cancer through inducing DNA damage and modulating immunosuppression [3]. Evidence suggests that this process may be modified by dietary factors including polyunsaturated fatty acids (PUFA). Elevated blood concentrations of omega-6 PUFA increase the levels of prostaglandin E2 (PGE-2), an immunoregulator associated with aggressive keratinocytic skin cancer growth [6, 7]. Omega-3 PUFA, eicosapentaenoic acid (EPA), has anti-inflammatory effects in skin post-UVR exposure, reducing sunburn sensitivity and PGE-2 levels [3, 8] and preventing DNA damage [9]. Because EPA is in constant competition for metabolism with the omega-6 arachidonic acid, the ratio of omega-3/6 in circulation plays a key role in determining the overall effect on skin photocarcinogenesis [5]
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