BACKGROUND
MSC still remains the most common cancer in the United States,4 with its incidence increasing in both men and women under the age of 40. There is an estimated 3.5 million cases of NMSC diagnosed in 2 million people in the United States, which equates to a more than 300% increase in NMSC incidence from 1994 to 2015.4-7 More than 2.8 million new cases of basal cell carcinoma (BCC) and 1 million new cases of squamous cell carcinoma (SCC) are diagnosed annually in the United States,2,6 costing 8.1 billion healthcare dollars annually.4 Exposure to ultraviolet (UV) radiation remains the biggest risk factor for the development of skin cancer, and people are receiving more UV radiation today than ever be- fore.7-9 Lifestyles where more time is spent outdoors, an erod- ing ozone layer, and a generally aging population with more cumulative sun damage have all contributed to this increased UV exposure.9,10 Traditionally, skin cancer prevention has focused on sun protection, and recommendations have included wearing protective clothing, using sunscreens with a sun protective factor of 30 or higher, and avoiding the sun.11 However, because skin cancer incidence continues to rise, additional preventative methods beyond photoprotection alone, more specifically, methods that repair past DNA damage, are needed. Through myriad mechanisms, non-prescription and prescription medications, administered orally, may play a role in skin cancer prevention (Table 1).
Decreasing DNA Damage Through Antioxidant Supplementa- tion and Low-Fat Diet
Carotenoids Free radicals produced from both by-products of cellular me- tabolism and environmental toxins damage DNA, and as damage accumulates, cancers may develop. By neutralizing free radicals, carotenoids can assist in cancer prevention.12-14 Concerning skin cancer specifically, carotenoids like lutein and zeaxanthin have been shown, both in murine and human mod- els, to provide significant protection against UV-induced skin injury by reducing mast cell infiltration, edema, and epidermal hyperplasia from UV exposure.14,15 Moreover, irradiated mice receiving dietary lutein and zeaxanthin grow fewer and smaller tumors and have increased tumor-free survival durations when compared to controls.14 The protective effects of oral antioxidants have been shown in human populations as well. In a cohort of Australian patients with a history of skin cancer, high dietary intake of lutein and zeaxanthin (2.9 mg/day) for 6 months in duration was associated with a more than 50% reduction in risk of SCC in 294 persons with a previous history of SCC (n=90), BCC (n=191), and unknown skin cancer (n=46) during an 8-year follow-up pe- riod.15 Analysis according to specific past history of SCC was not possible due to the small number of persons (n = 90) known to have a previous SCC before the initial skin examination. Further, after multivariate adjustment, the intake of lutein and zeaxanthin exhibited an inverse trend with SCC risk. In anoth- er study conducted in a similar population of 1,056 Australian adults, there was an inverse association between a 6-month period intake of green leafy vegetables (31g/day), a source of lutein and zeaxanthin, and risk of SCC over an 11-year follow-up period.16 Likewise, these results were only seen in those with a previous history of SCC. In both studies, no side effects were reported.15,16 While these studies suggest that oral antioxidants may be helpful for preventing SCCs, data for BCC prevention remains less clear. Some studies have shown decreased risk of BCCs, while others have shown the opposite.13,14 Additional
