Severe Sunburn Triggers the Development of Skin Cancers: Non-cumulative/Overwhelming UV Damages, UVA Rays, Human Papillomavirus, Indoor/Outdoor Workers and Animal Models

Abstract

Based on analysis of published data of incidence of melanoma, basal cell carcinoma and squamous cell carcinoma from 2 large prospective cohort studies involving about 120,000 health workers in USA, excellent linear relationships between skin cancer incidence and Severe Sunburn (SS) incidence suggesting their causal association were found. It is postulated that the SS-caused UV radiation overwhelms the skin cell’s capacity to repair/remove DNA lesions (about 70,000 non-cumulative lesions per day) and any of these un-repaired/un-removed lesions can eventually become a pre-cancerous tumor or cancer after overcoming numerous barriers of body’s repair/defense mechanisms. The above rationale for cancer etiology seems consistent with the classical wound-to-tumor doctrine. Infection with Human Papillomavirus will reduce the threshold for non-cumulative DNA lesions thereby facilitating cancer initiation. The proposed SS theory may be generally applicable to people with different races, skin types, hair colors and sunlight exposures. The proposed non-cumulative UV damage concept is supported by published data showing parallel first-order aging kinetics of human skin being exposed and un-exposed to sunlight in ordinary people. Solar UVA only plays a minor or insignificant role in skin cancer and premature aging. Prevalence of SS is reviewed. Controversies on skin cancer risks for indoor and outdoor workers such as airplane pilots and crew, health workers, gardeners and truck drivers are discussed. Potential shortcomings of a common practice of using highly unphysiological UV, UVA or UVB doses in animal, cell culture or human skin studies are discussed. Demonstration resembling the reversibility of intrinsic skin aging using a plant deprived of and then replenished with water is presented. It is hoped that this apparently provocative work may stimulate further discussions in the literature.