The main environmental risk factor for Actinic keratosis (AK), Bowen’s disease (BD) and squamous cell carcinoma (SCC) is ultraviolet radiation (UVR) and therefore photoprotection is always advisable. |
Nevertheless, other host, environmental and lifestyle factors play a relevant role in the onset of AK and BD and progression to invasive SCC. |
S. aureus infections, alcohol, tobacco, human papillomavirus, chemical contaminants and air pollution are clearly associated with AK and SCC development. |
Bowen’s disease is also associated with human papillomavirus infections and arsenic exposure. |
Caloric restriction of fat intake, oral nicotinamide, moderate consumption of red wine and green leafy vegetables are beneficial to prevent AK and SCC. |
Introduction
Methodology
Influential Role of Exposome Factors
Exposome | Subclassification | Specific factors | Risk/association | References | ||
---|---|---|---|---|---|---|
AK | BD | SCC | ||||
Host | Microbiome | S. aureus | ↑ | – | ↑ | |
Propionibacterium, Malasezzia | ↓ | ↓ | [34] | |||
Hormones | Higher serum vitamin D | – | – | ↑ | ||
– | – | ↓ | [53] | |||
PPARα, PPARγ | ↓ | – | ↓ | [58] | ||
PPARδ | ↑ | – | ↑ | [58] | ||
Nutritional | Fatty acids | Calorie restriction of fat | ↓ | – | ↓ | [65] |
High-fat diets | – | – | ↑ | |||
Oily fish (moderate intake) | ↓ | – | – | |||
Vitamins & minerals | Green leafy vegetables | – | – | ↓ | ||
Vitamin B3 | ↓ | – | ↓ | |||
β-Carotene | – | – | ↓ | [86] | ||
Vitamin C | – | – | ↓ | [86] | ||
Retinol | – | – | ↓ | [91] | ||
Selenium | – | – | ↑ | [92] | ||
Lifestyle | Alcohol & tobacco | Wine | ↓ | – | – | [74] |
Alcohol | ↑ | – | ↑ | |||
Tobacco | – | – | ↑ | |||
Environmental | Viral infections | HPV | ↑ | ↑ | ↑ | |
Merkel cell polyomavirus | – | ↑ | – | [132] | ||
Chemical contaminants | Arsenic | ↑ | ↑ | ↑ | ||
Coal tar, soot | ↑ | – | ↑ | [140] | ||
Paraquat | ↑ | – | ↑ | |||
Air pollution | PM | – | – | ↑ | [153] | |
PAH | – | – | ↑ | |||
Ozone depletion | – | – | ↑ | [169] |
Host Factors
Skin Microbiome
Hormones
Nutritional Factors
Quality and Quantity of Free Fatty Acid Consumption
Antioxidant and Vitamin Intake
Reference | Type of study | No. of individuals | Vitamins and minerals analysed | Main outcome |
---|---|---|---|---|
Kune et al. [86] | Case–control study | 88 cases + 88 controls | β-Carotene and vitamin C serum concentration | β-Carotene- and vitamin C-containing foods appear to be protective for both SCC and BCC. Cases had a lower mean serum level of β-carotene (p < 0.001) and vitamin A (p = 0.02) |
Karagas et al. [87] | Nested case–control study | 132 cases + 264 controls | Selenium, α-tocopherol, β-carotene and retinol serum concentration | No association was found between the concentrations of any of these nutrients and SCC |
Frieling et al. [88] | Randomized, double-blind, placebo-controlled trial | 22,071 | 12 years of 50 mg of β-carotene supplementation on alternate days | An average of 12 years of supplementation with β-carotene does not affect the development of both BCC and SCC |
Green et al. [89] | Community-based randomized controlled trial | 1621 | 30 mg of β-carotene supplementation per day | No beneficial or harmful effect on the rates of SCC and BCC as a result of β-carotene supplementation |
Greenberg et al. [90] | Randomized clinical trial | 1805 | 50 mg of β-carotene supplementation per day | In persons with a previous nonmelanoma skin cancer, treatment with β-carotene does not reduce the occurrence of new skin cancer over a 5-year period |
Moon et al. [91] | Randomized, double-blind, controlled trial | 2297 | 25,000 IU of oral retinol supplementation per day | Daily supplementation with 25,000 IU of retinol was effective in preventing SCC, although it did not prevent BCC |
Duffield-Lillico et al. [92] | Double-blind, randomized, placebo-controlled clinical trial | 1312 | 200 µg daily selenium supplementation | Selenium supplementation is ineffective at preventing BCC and it increases the risk of SCC and total NMSC |