Skin cancers are divided into three main types of Basal cell carcinoma, Squamous cell carcinoma and Melanoma, based on the abnormal cell development and proliferation of the type of skin cells. While Basal-cell carcinoma grows slowly and is more localized to the skin tissue, Squamous-cell carcinoma is more aggressive and malignant and can lead to metastatic far distance spread to other body tissues and could be fatal. Melanomas that arise from the melanocytes or skin pigment cells, are the most aggressive, malignant and metastatic, that killed Bob Marley.
While the sun is the source of life on earth and our own life in different aspects depend on its shinning, such as regulation of our circadian rhythm, sleep-wake cycle, and the color of our skin, its excess could contribute to more than 90% of skin cancers cases. The risk nowadays are higher due to a thinner ozone layer, and also the increase fad of artificial tannings as another common source of ultraviolet radiation. The longer and more intense exposures, such as from childhood and the sensitivity of the skin’s subject, for example the white skins, the living zones, such as regions with intense sunshine like Australia and New Zealand, and also the less defensive immune system, the more risk of cancer. (1-2)
Despite all these, and the skin cancer being the most common of all cancers world wide, the early intervention of the skin cancers, even melanoma through removal of the locus of the cancer such as the mole, radiotherapy and medications, have increased the survival rate of all the skin cancers higher than other cancers, close to 90% recovery rate. That takes us to the sad story of Bob Marley, who due to his religious beliefs, refused the full treatment of his melanoma on his toe from 1977, so the cancer spread to his brain and killed him mercilessly on 11 May 1981, at age only 36 and deprived the whole art of music and his global friends form a longer legendary career. (3-5)
Bob Marley, a musical icon, the father of reggae and an international messenger of love and peace, who started with band “The Wailers” , and a national symbol for Jamaica, with all his spirituality, yet could not survive from a small mole on her toe that finally spread to his brain and killed him. His songs such as “One love”, “Is this Love”, “Redemption Song”, “Waiting in Vain”, “Satisfy my Soul”, “O’Woman don’t cry”, “Buffalo Soldier”, “I shot the Sherriff”, “Jamming” and more has no need for an introduction as he is know and loved still to this day by billions. He could easily be the only human’s messenger and representation in popular music and culture. Unfortunately his religious commitment to Rastafari, not to allow the amputation of his cancerous toe so to prevent the spread of the melanoma, deprived him of such a great life and his fans to enjoy his music years longer.
Sunlight: Good, Bad and Ugly
The factor(s) or pathophysiology underlying the causation of all skin cancers by sunlight or UV (Ultra-Violet) radiation lies in the sensitivity of the skin (being fair) and the degree and the loci of radiation. So the incidence of all skin cancers even melanoma is higher among white population and in regions with the higher intensity of sun radiation such as Australia, or whites living in tropics and subtropics. Even in US, the incidence of melanomas are 10% among blacks compared with the white population. In fact melanomas in the blacks and Asians tend to occur at sites not exposed to the sun, such as the nail beds and sole of the foot, that happened to Bob Marley. (6)
In the cases of black and Asians’ sun unexposed melanomas and in the cases of sun exposed skin cancers, there seem to be the underlying pathophysiology of gene or germ-like mutations such as in CDKN2A gene. The sun radiation in whites, and physical traumas to the nail beds and foot in the blacks and Asians as insults, damage the DNA of the Basal, Squamous and melanocyte skin cells, leading to the skin cancers. This theory has been supported by higher incidence of all skin cancers in the patients with “Xeroderma Pigmentosa” a familial disease, deficient in repair of DNA photoproducts induced by UV radiation. (7)
In fact skin cancer is an optimal model for learning the process and pathophysiology of cancer in general across the human organs and tissues. Since the insult or trauma by the sun light in more than 90% of skin cancer cells has been confirmed as the main predisposing factor, the skin is an easier platform to study the evolution of cancer. Moreover the skin sensitivity such as in whites and also aging are other know factors that with the UV light complete the puzzle of skin cancer development. What are these skin sensitivities in the while population and aging at a cellular and molecular level that rise to the evolution of cancer?
As briefly alluded to earlier, these susceptibilities are gene mutations, that surprisingly exist in the so called normal looking skin cells and tissue in sensitive individuals more than others. Actually about 20% of normal skin cells carry such mutations matching cancer. Many of these mutation genes do not evolve to be cancerous, as a strong positive selection, in Darwinian model, protect the normal physiology of the skin. Even in the aged, white and sun-exposed skin, only 25% of the skin cells carrying cancer-causing mutations evolve to malignancy. This pathophysiological process has been also observed in other malignancies such of blood cells, where somatic mutations, including some driver mutations, have been found to accumulate at a low rate with increasing age. (8-10)
Other than sun or UV light as discussed as the predisposing factor in evolution of all skin cancers, in sun unexposed skin such as fingers and toe nail beds, and in black population, trauma could trigger cancer development. This hypothesis, though not as strong as the trauma by the sunlight has been observed in clinical cases and could have true in the case of Bob Marley. In these cases there has been continuum of the initial traumatic lesion as well as topographic correspondence between the initial trauma, the remaining dystrophy and the appearance of the melanoma. This has been true for specific melanomas such as acral melanoma with a high relative risk that is multiplied for repeated trauma, suggesting a “dose-effect” relationship. Trauma could act as the promotional stage of melanoma mediated by cytokines released during wound healing or it could cause direct activation of micro-vascular tumour cell transport. (11-12)
As mentioned briefly earlier, other than sun exposure, nowadays indoor tanning has become a risk factor in the development of skin cancers. The population attributable risk fraction in the United States for such risk factor has been estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma. This corresponds to more than 170, 000 cases of non-melanoma skin cancer each year attributable to indoor tanning. The risk has been higher with earlier age use, so that indoor tanning before age 25 has been more strongly associated with all both squamous cell, basal cell carcinomas and melanoma. (4, 13-14)
In summary, skin cancer while it is the most common of all human’s cancer, it is very much preventable and treatable. The prevention of the skin cancers is more so important and imperative in the susceptible populations such as whites, specially those living in intense sunshine regions of the world. The sufficient application of suntan lotions and avoidance of long-term or hours of exposure is another preventive measures. The elderly population need to be aware and educated about their higher risk. The use of tan salons and exposure to the artificial UV lights, just for the sake of appearance specially in young white population who are at higher risk needs to be avoided. Finally the traumas, specially repeated ones in non-white population or all, in sun non-exposed body areas such as nail beds, specially in the presence of nevi, need to watched out. In case of happening, the hasty treatment of the skin cancer locus by excision of the area or farther, for example the whole toe or foot is mandatory, before the metastasis of the cancer to the rest of body as they could be quite invasive, specially with melanomas, that unfortunately happened to the great Bob Marley.
Dr.Mostafa Showraki, MD, FRCPC Lecturer, School of Medicine, University of Toronto Author: ADHD: Revisited Book, Amazon Kindle Books www.adhdrevisited.com/www.medicinerevisited.com
- Marcil I, Stern RS. Risk of Developing a Subsequent Nonmelanoma Skin Cancer in Patients With a History of Nonmelanoma Skin Cancer.A Critical Review of the Literature and Meta-analysis. Arch Dermatol. 2000;136(12):1524–1530.
- Feller L, Khammissa RAG, Kramer B, Altini M, Lemmer J. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face. Head & Face Medicine. 2016;12:11.
- D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV Radiation and the Skin. International Journal of Molecular Sciences. 2013;14(6):12222-12248.
- Wehner MR, Shive ML, Chren M-M, Han J, Qureshi AA, Linos E. Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis. The BMJ. 2012;345:e5909.
- Surdu S, Fitzgerald EF, Bloom MS, et al. Occupational Exposure to Ultraviolet Radiation and Risk of Non-Melanoma Skin Cancer in a Multinational European Study. Toland AE, ed. PLoS ONE. 2013;8(4):e62359.
- Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. Engl J Med. 1999 Apr 29;340(17):1341-8.
- Pudroma X, Duoji G, Grigalavicius M, Jie D, Juzeniene A. Molecular Mechanisms of UVA-Induced Melanoma. J Environ Pathol Toxicol Oncol. 2017;36(3):217-228.
- Martincorena I, Roshan A, Gerstung M, et al. High burden and pervasive positive selection of somatic mutations in normal human skin. Science (New York, NY). 2015;348(6237):880-886.
- Nowell PC. The clonal evolution of tumor cell populations. 1976 Oct 1; 194(4260):23-8.
- Welch JS, et al. The origin and evolution of mutations in acute myeloid leukemia. 2012 Jul 20; 150(2):264-78.
- Lesage C, Journet-Tollhupp J, Bernard P, Grange F. Post-traumatic acral melanoma: an underestimated reality?. Ann Dermatol Venereol. 2012 Nov;139(11):727-31.
- Juten PG, Hinnen JW. A 71-year-old woman with a pigmented nail bed, which persisted after trauma. Acta Chir Belg. 2010 Jul-Aug; 110(4):475-8.
- Gallagher RP, Spinelli JJ, Lee TK. Tanning beds, sunlamps, and risk of cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev2005;14:562-66.
- International Agency for Research on Cancer Working Group on Artificial Ultraviolet (UV) Light And Skin Cancer. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int J Cancer2007;120:1116-22.