Association of Nonmelanoma Skin Cancer with Second Malignancy
The Women's Health Initiative Observational Study T he extremely interesting publication by Rosenberg et al. 1 assessed the enhanced risk of a second malignancy associated with nonmelanoma skin cancer (NMSC) in 93,766 women. The authors found that women with a history of NMSC were more than twice as likely to report a second other tumor compared with those who experienced no NMSC. This article 1 differed from similar earlier reports because the sample was large and geographically and ethnically disparate and confounding variables were considered.
The authors described numerous potential mechanisms that might explain the connection between NMSC and other cancers. Because ultraviolet (UV) exposure is the main risk factor for skin cancer, they described how UV exposure might influence the second malignancies (DNA repair, p53 gene mutations, etc.). They noted photoimmune suppression as a likely mechanism. One photoreceptor in skin that has been proposed for the initiation of photoimmune suppression is trans-urocanic acid (UCA). 2 Photoimmune suppression is local and systemic and often is measured by a loss of hypersensitivity. Photoimmune suppression also has been demonstrated to increase infection by 15 pathogens in animls. 2 Rosenberg et al. found that in black women, those with NMSC had 7.46 times the odds of reporting another malignancy compared with black women without NMSC. They also state that black women with a history of NMSC may be at an even greater relative risk (3.34) compared with white women with NMSC. The authors suggest that this result may indicate ethnic differences with regard to immunity. 1 My suggestion is that this ethnic difference may be related to the concentration of UCA in the skin.
There is limited evidence that black individuals have a higher concentration of total skin UCA compared with white persons. Kral et al. 3 compared the UCA content of Africans and Europeans. The Africans came from eight countries near the equator. They had statistically significantly higher levels of UCA (5.1 g/mg for Africans; 2.95 g/mg for Europeans). Another report in 1994 indicated that the UCA content in the skin of black Africans is greater than three times higher than that in white skin. 4 However, more research concerning this finding is needed.
There is good evidence in mice that the UCA concentration in the skin affects an individual's susceptibility to photoimmune suppression. 5 These studies manipulated skin UCA to both higher and lower levels.
The hypothesis is that black individuals have more total UCA in the skin and therefore experience more photoimmune suppression, which contributes to increased susceptibility to a second malignancy.
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