Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen’s Disease and Squamous Cell Carcinoma: A Proposal

Abstract

Actinic keratosis (AK) is the main risk factor for the development of cutaneous invasive squamous cell carcinoma (SCC). It represents the first sign of severe chronic ultraviolet radiation exposure, which has a clear significant effect. Nevertheless, the skin is exposed to many other exposome factors which should be thoroughly considered. Our aim was to assess the impact of exposome factors other than ultraviolet radiation (UVR) on the etiopathology of AK and Bowen's disease (BD) and progression of AK to SCC and to design tailored prevention strategies. We performed an exhaustive literature search in September 2021 through PubMed on the impact of exposome factors other than UVR on AK, BD and SCC. We conducted several parallel searches combining terms of the following topics: AK, BD, SCC and microbiome, hormones, nutrition, alcohol, tobacco, viral infections, chemical contaminants and air pollution. Notably, skin microbiome studies have shown how Staphylococcus aureus infections are associated with AK and AK-to-SCC progression by the production of chronic inflammation. Nutritional studies have demonstrated how a caloric restriction in fat intake, oral nicotinamide and moderate consumption of wine significantly reduce the number of premalignant keratoses and SCC. Regarding lifestyle factors, both alcohol and smoking are associated with the development of SCC in a dosedependent manner. Relevant environmental factors are viral infections and chemical contaminants. Human papillomavirus infections induce deregulation of cellular proliferation and are associated with AK, BD and SCC. In addition to outdoor jobs, occupations such as industrial processing and farming also increase the risk of developing keratoses and SCC. The exposome of AK will undoubtedly help the understanding of its etiopathology and possible progression to

Influence of environmental risk factors on the development of wounds associated with squamous cell carcinoma

“…Frequent exposure to carcinogenic substances was linked to the significantly increased risk of SCC development. In certain professions, occupational or environmental exposure to carcinogens may contribute to the initiation and progression of SCC lesions 22 . In high‐risk environments, enhanced safety measures and stringent regulations are required to reduce exposure.…”

Skin microbiome in cancer patients with pruritus and other skin toxic reactions related to anticancer therapy: A review

“…Выживание Propionibacterium, обычной бактерии, колонизирующей кожу при акне, зависит от выработки кожного сала, и уменьшение ее присутствия может усугубить тяжесть высыпаний вследствие нарушения гомеостаза микробиома и стимулирования роста S. aureus [9]. И наоборот, S. aureus может быть причиной прогрессирования AK и трансформации АК в ПКРК посредством индукции хронического воспаления с выработкой оксида азота и цитокинов, которые способствуют канцерогенезу [11].…”

Effects of Air Pollution on Cellular Senescence and Skin Aging

“…PM causes inflammation in the skin through increased IL-8, MMP-1, ROS production, and neutrophil infiltration in the deep dermis [ 104 ]. Fibroblasts cultivated with conditioned medium obtained from immortalized human keratinocytes (HaCaT) treated with PM displayed increased nuclear translocation of p65 and p50 as well as increased ROS production, morphological changes, and secretion of SASP components including prostaglandin E2, COX-2, TNF-α, IL-1β, and IL-6 [ 93 ].…”

“…A report has shown that in human keratinocytes, exposure to ozone leads to lactate dehydrogenase release, reduced cell proliferation, lipid peroxidation, and NF-κB activation and these effects can be prevented by pretreatment with antioxidant mixtures [ 123 ]. Another study has shown that the combination of UVA and ozone has a synergistic effect and causes increased oxidative stress of the skin and Nrf2 expression in keratinocytes leading to skin inflammation, formation of wrinkles, and pigment spots [ 8 , 9 , 104 ]. In human skin O 3 leads to activation of NF-κB, MMP-9, COX-2, and lipid peroxidation in the epidermis, whereas in the dermis expression of collagen-1 and -3 are downregulated.…”