Ultraviolet A radiation exposure and melanoma: a review : Melanoma Research

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Ultraviolet A radiation exposure and melanoma: a review

Fadadu, Raj P.a,b; Wei, Maria L.a,b

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doi: 10.1097/CMR.0000000000000857
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Abstract

Introduction

Cutaneous melanoma is an aggressive form of skin cancer that arises from the malignant transformation of melanocytes, which can be promoted by exposure to ultraviolet radiation (UVR) [1]. In 2020, melanoma was estimated to have a global incidence of 325 000 cases and lead to 57 000 global deaths [2]. Globally, the number of melanoma cases is increasing, and disease incidence is associated with geography, which may suggest environmental influences [3]. Age-standardized incidence rates are higher in areas of low latitude that are closer to the equator, a phenomenon termed the ‘latitude gradient’ [4,5]. Changes in latitude and altitude reflect differences in cloud coverage, ozone absorption and surface reflectance, which are all factors that impact the intensity of UVR exposure [6,7]. Climate change is predicted to have a complex interaction with surface level UVR [8]; the trend of increasing incidence of cutaneous melanoma has also been attributed to other factors, such as increased diagnostic scrutiny [9,10].

Sunlight includes three components: ultraviolet C (UVC) radiation (200–290 nm), ultraviolet B (UVB) radiation (290–320 nm) and ultraviolet A (UVA) radiation (320–400 nm), which is further subdivided into UVA1 (340–400 nm) and UVA2 (320–340 nm). While UVB waves carry greater energy, UVA penetrates deeper into the skin [11,12]. The association between UVB exposure and increased risk for skin cancers has been well established [13,14]. DNA directly absorbs UVB radiation, resulting in photoproducts, such as cyclobutane dimers and 6–4 photoproducts, nucleotide transversions, DNA strand breaks and UV-induced apoptosis [15–18]. Animal and epidemiology studies bolster the positive association between UVB exposure and melanoma occurrence [19–21]. However, there have been relatively fewer studies conducted that focus on the role of UVA exposure in the development of skin cancers.

The role of UVA in melanomagenesis is important to study because stratospheric ozone absorbs most of the UVB radiation but little UVA radiation [22,23], such that UVA radiation comprises approximately 94% of UVR reaching the earth’s surface; additionally, UVA exposure, compared to UVB, starts earlier and ends later each day and is more continuously present throughout the year, especially during winter months at higher latitudes [24–26]. The increasing global incidence of melanoma adds public health urgency to understanding UVA’s role in the carcinogenesis of melanocytes, as UVA exposure can be reduced or prevented with policies on sunscreen products and indoor tanning [27,28].

Prior review articles on UVA exposure and melanoma focused on either molecular or epidemiologic evidence and did not include more recently published evidence [6,29–31]. Here, we provide an updated review that includes recent studies on the relationship between UVA and melanomagenesis across cell, animal and epidemiology studies, which overall, suggest a significant association.

Molecular and cellular biology studies

Studies conducted on human skin cells have demonstrated important elements of UVA’s photobiology [31,32]. Molecular studies reviewed here determined that UVA exposure plays a role in the development of melanoma; reports studied cells from a variety of sources: cell lines [32], foreskin samples [33–35], reconstructed three-dimensional human skin equivalents [36] or in situ irradiated skin before biopsy [37]. Various cellular molecules are capable of absorbing UVA radiation, but most studies focused on DNA. UVA can cause direct DNA damage, generate harmful reactive oxygen species (ROS), and dysregulate gene expression. The extent of DNA damage can be detected by the levels of apoptotic proteins expressed and is associated with impairment of DNA repair systems [38,39], most often resulting from oxidative damage of proteins involved in nucleotide excision repair [6,40].

The mutagenic potential of UVA is in small part related to its direct effects on DNA. Similar to the formation of pyrimidine dimers following UVB exposure, UVA radiation has been found to form mutagenic photoproducts in genomic DNA, including cyclobutane pyrimidine dimers (CPDs), (6–4) pyrimidine photoproducts (64PPs) and Dewar valence isomers [31]. Investigators in one study examined direct DNA damage by irradiating separate areas of healthy volunteers’ buttocks with increasing doses of UVA I (360–450 nm) and UVA I + II (320–400 nm). Immunohistochemistry performed on biopsied cells to assess DNA damage sustained in vivo illustrated a high expression of thymine dimers in the in situ UV-irradiated skin [37]. Similarly, other studies have found that UVA exposure increased the production of thymine cyclobutane dimers hours after exposure, and one showed high induction of direct strand breaks in both melanocytes and keratinocytes [36,41–43]. Impaired DNA repair responses for the removal of UVA-induced CPDs in melanocytes could contribute to the progression of melanoma [44,45]. Additional UVA-induced damages to DNA include gaps and breaks, but the role of UVA in melanoma development may not be primarily due to direct DNA damage [34].

Melanocytes have been found to be more resistant to direct DNA changes caused by UVA exposure than other types of skin cells, and the production of CPDs by UVA irradiation is not as extensive as the damage incurred by UVB [32,36]. One study compared the UV spectrum for the formation of pyrimidine dimers with that for the formation of 8-oxo-2’-deoxyguanosine (8-OhdG) species – products of oxidative DNA base damage – in skin cells [41]. While the peak for the pyrimidine dimers was in the UVB range, the formation of 8-OhdG peaked in the UVA range. The authors suggested that the induction of 8-OHdG species occurs independently of direct absorption of UVA by DNA. Instead, it can be related to the UVA-mediated production of singlet oxygen, a major ROS that causes oxidative damage to cellular molecules [46,47].

ROS generated by UVA radiation can damage DNA through forming single-strand breaks, oxidized purines and pyrimidines and protein-DNA crosslinks, which could result in the development of melanoma, but the exact pathway is still unclear [31,46]. The induction of 8-OHdG in fibroblasts was found to increase linearly in a dose-response fashion with the intensity of broadband UVA irradiation [46]. A follow-up study with melanoma cells concluded that the process of melanin synthesis, but not the mere presence of melanin itself, increased the susceptibility of DNA to oxidative damage by UVA [47]. Another study demonstrated that the effects of UVA on DNA structure can be indirectly due to ROS acting on fragments of melanin, which can then transfer energy to DNA, causing CPD generation hours after UVA exposure in melanocytes, especially when DNA repair mechanisms are suppressed [43]. This reveals a melanin-dependent pathway for melanomagenesis, which is paradoxical given that melanin is typically considered protective for skin carcinogenesis [48]. Other UVA irradiation studies found that melanocytes accumulated more oxidative products compared to keratinocytes and that UVA radiation was noted to have greater oxidative effects on melanocytes compared with UVB, consistent with UVA playing a greater role in indirect DNA damage [33,41]. Furthermore, non-UVA-exposed melanocytes have also been shown to exhibit ‘bystander’ oxidative stress via soluble factors generated by UVA-irradiated keratinocytes or fibroblasts [32]. This indicates that an underlying mechanism of melanomagenesis by UVA may be through the production of ROS in neighboring cells as well as melanocytes. In addition, UV-related ROS and Akt kinase signaling can affect metabolic processes that promote carcinogenesis; increased glucose consumption and lactic acid production promotes immune escape and expression of tumor-relevant proteases [49,50].

UVA exposure has downstream effects on processes such as transcription, translation and cell division [51,52]. One study provided evidence for UVA’s carcinogenic role by noting increased production of proteins that promote tumorigenesis in melanocytes irradiated with UVA [51]. UVA-exposed melanocytes from foreskin overexpressed p73 and Nup88; Nup88 overexpression induces aneuploidy and chromosomal instability whereas overexpression of p73 is associated with vascular invasion [53]. In addition, human melanocytes irradiated with 365 nm UVA were found to upregulate genes encoding transcription factors and those involved in cell cycle regulation, the stress response and apoptosis – hallmarks of cellular damage [35]. Consistent with these findings is the report of UVA-mediated G1 cell cycle arrest in melanocytes [34]. Furthermore, in situ UVA irradiation of human skin increased the expression of the p53 protein, which is implicated in melanocyte cell cycle regulation and increased thymidine dimer formation in the basal layer of the epidermis, where melanocytes reside [37,54]. Finally, increased plasma membrane instability has been reported as a result of UVA-induced damage to melanocytes [33].

Animal model studies

Understanding how UVA exposure contributes to melanoma occurrence in an animal model can provide some insight into the same relationship in humans. We found studies conducted with fish, opossum and mice. Of these, three studies conducted with transgenic mice and one with crosses of platyfish found that these animals had a risk of developing melanoma when exposed to UVA [43,52,55,56]. Van Schanke et al. [52] reported the detection of increased numbers of p53 expressing cells in the basal layer of the epidermis of hairless SKH-2 mice irradiated with UVA, indicating a DNA damage response at epidermal levels where melanocytes reside in humans. However, in contrast to humans, mice normally have no epidermal melanocytes, so the direct effect on melanocytes could not be assessed in this model [56]. Using transgenic mice with melanocytes in the epidermis, mimicking human skin, Premi et al. [43] found continued generation of CPDs in the mouse melanocytes for at least 3 h after in-vivo UVA exposure, in part due to UVA-induced ROS. Other researchers, also using mice with epidermal melanocytes, found that UVA-induced melanoma, attributed to oxidative DNA damage, in a melanin pigment-dependent mechanism [55]. This is consistent with the pigment-dependent mechanism of UVA-mediated melanomagenesis found in the in-vitro studies described above [43].

Some studies conducted with opossum and fish did not demonstrate a direct connection between UVA and melanoma but did report UVA effects on melanocytes [57,58]. Among 856 sucklings irradiated with UVA radiation at various doses, only one, in the high-intensity radiation group, developed a melanocytic lesion [57]. Another study found that the highest dose of UVA administered to opossum gave a statistically significant induction of focal melanocytic hyperplasia [58]. These studies, while not directly linking UVA to melanoma development, did demonstrate adverse effects of UVA on melanocytes. Setlow et al. [56] found that the fraction of fish with tumors increased as exposure to UVA radiation increased, providing what was considered seminal evidence for the melanoma-inducing effects of UVA. However, a later study was unable to replicate these results and found that the number of melanomas induced by UVA was not increased above the number observed in nonirradiated fish; this study re-analyzed the Setlow study results and concluded that the former study did not have adequate numbers of fish to power statistical reliability [59]. While there are similarities between the structure of the skin in these animals and humans, interspecies generalizability of these findings should be taken with caution. For example, humans lack melanophores as well as other biological features that fish have in their skin, and opossums lack the epidermal melanocytes that humans have, which can impact melanoma susceptibility [55].

Epidemiology studies

Epidemiology studies have examined the relationship between UVA exposure and melanoma at a human population level [30]. We reviewed five primary research articles on psoralens and UVA (PUVA) treatment and geography and also discussed findings from five meta-analyses that each included from 10 to 40 observational studies on indoor tanning. Researchers determined individuals’ level of UVA exposure based on geographic location, use of tanning devices that emit UVA radiation [60] or medical treatment with PUVA. The overall data from epidemiology studies predominantly suggest UVA as a risk factor for melanoma development. They have provided evidence for the International Agency for Research on Cancer’s classification of the full range of UV spectrum and artificial UV-emitting devices as carcinogenic in 2009 [30,61,62]. Policies created after this announcement have successfully reduced the prevalence of indoor tanning device use [63].

Significant, positive associations between exposure to indoor tanning devices and melanoma have been reported. Four meta-analyses of observational studies on indoor tanning and melanoma, published in 2012, 2014, 2019 and 2021, found consistent results: a summary relative risk of 1.25 [95% confidence interval (CI), 1.08–1.43], odds ratio of 1.16 (95% CI, 1.05–1.28), relative risk of 1.38 (95% CI, 1.22–1.58) and relative risk of 1.27 (95% CI, 1.16–1.39), respectively [64–67]. The summary measures of association were greater for early-onset skin cancer, if the first use of devices occurred at an earlier age (before 20 or 35 years) and if subjects attended more than 10 tanning sessions. Therefore, earlier and more frequent use of indoor tanning devices may increase the risk for melanoma development, suggestive of a dose-response relationship. One meta-analysis of studies before early 2016 found positive but statistically insignificant summary risk estimates [68]; however, the meta-analysis published in 2021 included more studies in total and focused on cohort studies, which provide a stronger level of evidence compared to the case-control studies [67]. Studies have found statistically significant associations for melanoma occurrence across different types of devices: conventional, high speed/intensity, high pressure and sunlamp [67,69]. In addition, indoor tanning is associated with the development of risk factors for melanoma (elevated nevus count, atypical nevi and lentigines) and lesions suspicious for melanoma [70]. Two recent cohort studies also found that younger female users of tanning devices later developed melanoma at an earlier age [71] and that indoor tanning device use increased risk for multiple primary melanomas [72]. Overall, epidemiology studies were found to vary in quality, but evidence for the carcinogenic effects of UVA included large study populations and accounted for cofounders such as hair color, number of nevi and skin pigmentation.

A similar pattern of increasing risk with a greater degree of UVA exposure was present in PUVA studies with longer follow-up. However, because PUVA typically involves the oral administration of the mutagen methoxsalen (8-methoxypsoralen) and UVA radiation in combination, it is harder to attribute observed health effects specifically to UVA exposure alone [73]. Two studies prospectively evaluated 1380 patients who received PUVA treatment in 1975 and 1976 for the occurrence of melanoma and found that both the dosage of PUVA and the number of phototherapy treatments were associated with a greater risk of developing malignant melanoma [73,74]. The incidence of melanoma began to increase approximately 15 years after patients’ first PUVA treatment, and the risk of disease occurrence increased over time thereafter, with a relative risk of 5.4 (95% CI, 2.2–11.1) [73]. This may explain why other researchers reported that PUVA was not significantly associated with an increased risk for melanoma in two prospective cohort studies of patients followed for a mean of approximately 14–16 years; study participants may not have been observed long enough to capture all cases of melanoma development [75,76]. This also applies for certain epidemiology studies on indoor tanning, in which tumor-induction time may have been insufficient, leading to an inaccurate risk estimation [60]. Challenges to conducting longitudinal studies on UVA and melanoma include an accurate UVA exposure assessment and the prolonged follow-up interval needed for outcome assessment while accounting for confounders.

Finally, an ecologic study examined cutaneous malignant melanoma (CMM) incidence rates with respect to geographic location. Researchers conducted a worldwide analysis of CMM incidence in relation to calculated UVR exposure [11]. They determined that increasing doses of UVB radiation were not associated with CMM and, instead, UVA exposure may play a role in initiating and promoting CMM. This could be attributed to the lesser variation in UVA exposure with changing latitude, compared with UVB exposure, which has a greater decrease with increasing latitude [25].

Discussion

A review of the literature reveals a variety of cell, animal and epidemiology studies that investigated UVA radiation’s role in the development of melanoma. The data, taken together, suggest that UVA exposure is a risk factor for melanoma, with cell studies providing insight into the biological mechanisms of carcinogenesis, animal studies demonstrating in-vivo relevance and epidemiology studies exploring the role of UVA exposure for melanoma development in patients. Molecular studies have clearly highlighted that generation of ROS, leading to DNA damage and modifications to gene transcription, are potential pathways through which UVA radiation induces carcinogenic effects in melanocytes [32,35,55]. In addition, epidemiology studies examined large-scale effects on patients and primarily found UVA to be a risk factor for melanoma development, though the quality of these studies is variable. Several case-control and cohort studies that examined UVA exposure from indoor tanning bed use [67] and PUVA treatment [73] have found a significant positive correlation between exposure and melanoma, with evidence of a dose-response relationship [65]. The discrepancy in results for some epidemiology studies may be due to insufficient lag interval between exposure and outcome assessment and lack of control for confounders.

The overall positive link between UVA exposure and melanoma risk can help inform public health policies on sunscreens and indoor tanning. A significant number of European countries do not have sunbed/tanning bed legislation and legislation in the USA is patchwork, varying by state [77,78]. Exposure to UVA radiation could partially contribute to the increasing incidence of melanoma [30]. Regarding the regulation of sunscreens, the US Food and Drug Administration proposed new rules in February 2019 and September 2021 for increased UVA protection as sun protection factor rating increases and a specified ratio of UVA I (340–400 nm) to UV protection of 0.7 [79–81]. The US also has limited regulations on the use of indoor tanning beds, which primarily emit UVA radiation and are used by over 10 million consumers [82,83]. The European Union and WHO are already enacting strict policies to reduce artificial cosmetic tanning, and Brazil and Australia have banned commercial sunbeds [84]. The Sunbeds Act of 2010 significantly decreased the number of vulnerable youth in England using sunbeds; however, an estimated 62 130 children aged 11–17 years still use sunbeds [85]. Strong regulations limiting the use of indoor tanning devices may be more effective if they target users when they are younger [86] and can reduce skin cancer burden and health care costs [87,88]. Understanding the relationship between UVA exposure and the development of melanoma will assist in the implementation of policy and public health interventions to mitigate the incidence of melanoma.

Acknowledgements

Conflicts of interest

There are no conflicts of interest.

References

1. Sample A, He YY. Mechanisms and prevention of UV-induced melanoma. Photodermatol Photoimmunol Photomed 2018; 34:13–24.
2. Arnold M, Singh D, Laversanne M, Vignat J, Vaccarella S, Meheus F, et al. Global burden of cutaneous melanoma in 2020 and projections to 2040. JAMA Dermatol 2022; 158:495–503.
3. Matthews NH, Li WQ, Qureshi AA, Weinstock MA, Cho E. Epidemiology of Melanoma. In: Ward WH, Farma JM, editors. Cutaneous Melanoma: Etiology and Therapy [Internet]. Codon Publications; 2017. http://www.ncbi.nlm.nih.gov/books/NBK481862/
4. Glazer AM, Winkelmann RR, Farberg AS, Rigel DS. Analysis of trends in US melanoma incidence and mortality. JAMA Dermatol 2017; 153:225–226.
5. Lancaster HO, Nelson J. Sunlight as a cause of melanoma; a clinical survey. Med J Aust 1957; 44:452–456.
6. Pudroma X, Duoji G, Grigalavicius M, Jie D, Juzeniene A. Molecular mechanisms of UVA-induced melanoma. J Environ Pathol Toxicol Oncol 2017; 36:217–228.
7. Krishnamurthy S. The geography of non-ocular malignant melanoma in India: its association with latitude, ozone levels and UV light exposure. Int J Cancer 1992; 51:169–172.
8. Bais AF, McKenzie RL, Bernhard G, Aucamp PJ, Ilyas M, Madronich S, Tourpali K. Ozone depletion and climate change: impacts on UV radiation. Photochem Photobiol Sci 2015; 14:19–52.
9. Welch HG, Mazer BL, Adamson AS. The rapid rise in cutaneous melanoma diagnoses. N Engl J Med 2021; 384:72–79.
10. Swerlick RA, Chen S. The melanoma epidemic: more apparent than real? Mayo Clin Proc 1997; 72:559–564.
11. Godar DE, Subramanian M, Merrill SJ. Cutaneous malignant melanoma incidences analyzed worldwide by sex, age, and skin type over personal Ultraviolet-B dose shows no role for sunburn but implies one for Vitamin D3. Dermatoendocrinol 2017; 9:e1267077.
12. Pustisek N, Situm M. UV-radiation, apoptosis and skin. Coll Antropol 2011; 35 (Suppl 2):339–341.
13. Watson M, Holman DM, Maguire-Eisen M. Ultraviolet radiation exposure and its impact on skin cancer risk. Semin Oncol Nurs 2016; 32:241–254.
14. D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the skin. Int J Mol Sci 2013; 14:12222–12248.
15. Matsumura Y, Ananthaswamy HN. Molecular mechanisms of photocarcinogenesis. Front Biosci 2002; 7:d765–d783.
16. Cleaver JE, Crowley E. UV damage, DNA repair and skin carcinogenesis. Front Biosci 2002; 7:d1024–d1043.
17. Medrano EE, Im S, Yang F, Abdel-Malek ZA. Ultraviolet B light induces G1 arrest in human melanocytes by prolonged inhibition of retinoblastoma protein phosphorylation associated with long-term expression of the p21Waf-1/SDI-1/Cip-1 protein. Cancer Res 1995; 55:4047–4052.
18. Kulms D, Schwarz T. Mechanisms of UV-induced signal transduction. J Dermatol 2002; 29:189–196.
19. Ley RD. Animal models of ultraviolet radiation (UVR)-induced cutaneous melanoma. Front Biosci 2002; 7:d1531–d1534.
20. Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, Melchi CF. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer 2005; 41:45–60.
21. Patton EE, Mueller KL, Adams DJ, Anandasabapathy N, Aplin AE, Bertolotto C, et al. Melanoma models for the next generation of therapies. Cancer Cell 2021; 39:610–631.
22. Parisi AV, Igoe D, Downs NJ, Turner J, Amar A, Jebar MAA. Satellite monitoring of environmental solar ultraviolet A (UVA) exposure and irradiance: a review of OMI and GOME-2. Remote Sens 2021; 13:752.
23. Kerr JB, McElroy CT. Evidence for large upward trends of ultraviolet-B radiation linked to ozone depletion. Science 1993; 262:1032–1034.
24. Diffey BL. Sources and measurement of ultraviolet radiation. Methods 2002; 28:4–13.
25. Grigalavicius M, Moan J, Dahlback A, Juzeniene A. Daily, seasonal, and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer. Int J Dermatol 2016; 55:e23–e28.
26. O’Neill CM, Kazantzidis A, Ryan MJ, Barber N, Sempos CT, Durazo-Arvizu RA, et al. Seasonal changes in vitamin D-effective UVB availability in Europe and associations with population serum 25-hydroxyvitamin D. Nutrients 2016; 8:E533.
27. Coates SJ, McCalmont TH, Williams ML. Adapting to the effects of climate change in the practice of dermatology-A call to action. JAMA Dermatol 2019; 155:415–416.
28. Bharath AK, Turner RJ. Impact of climate change on skin cancer. J R Soc Med 2009; 102:215–218.
29. Wang SQ, Setlow R, Berwick M, Polsky D, Marghoob AA, Kopf AW, Bart RS. Ultraviolet A and melanoma: a review. J Am Acad Dermatol 2001; 44:837–846.
30. Autier P, Doré JF, Eggermont AM, Coebergh JW. Epidemiological evidence that UVA radiation is involved in the genesis of cutaneous melanoma. Curr Opin Oncol 2011; 23:189–196.
31. Khan AQ, Travers JB, Kemp MG. Roles of UVA radiation and DNA damage responses in melanoma pathogenesis. Environ Mol Mutagen 2018; 59:438–460.
32. Redmond RW, Rajadurai A, Udayakumar D, Sviderskaya EV, Tsao H. Melanocytes are selectively vulnerable to UVA-mediated bystander oxidative signaling. J Invest Dermatol 2014; 134:1083–1090.
33. Larsson P, Andersson E, Johansson U, Ollinger K, Rosdahl I. Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis. Exp Dermatol 2005; 14:117–123.
34. Kowalczuk CI, Priestner MC, Pearson AJ, Saunders RD, Bouffler SD. Wavelength dependence of cellular responses in human melanocytes and melanoma cells following exposure to ultraviolet radiation. Int J Radiat Biol 2006; 82:781–792.
35. Jean S, Bideau C, Bellon L, Halimi G, De Méo M, Orsière T, et al. The expression of genes induced in melanocytes by exposure to 365-nm UVA: study by cDNA arrays and real-time quantitative RT-PCR. Biochim Biophys Acta 2001; 1522:89–96.
36. Miyamura Y, Coelho SG, Schlenz K, Batzer J, Smuda C, Choi W, et al. The deceptive nature of UVA tanning versus the modest protective effects of UVB tanning on human skin. Pigment Cell Melanoma Res 2011; 24:136–147.
37. Burren R, Scaletta C, Frenk E, Panizzon RG, Applegate LA. Sunlight and carcinogenesis: expression of p53 and pyrimidine dimers in human skin following UVA I, UVA I + II and solar simulating radiations. Int J Cancer 1998; 76:201–206.
38. Brem R, Karran P. Multiple forms of DNA damage caused by UVA photoactivation of DNA 6-thioguanine. Photochem Photobiol 2012; 88:5–13.
39. Gaddameedhi S, Kemp MG, Reardon JT, Shields JM, Smith-Roe SL, Kaufmann WK, Sancar A. Similar nucleotide excision repair capacity in melanocytes and melanoma cells. Cancer Res 2010; 70:4922–4930.
40. Emri G, Paragh G, Tósaki Á, Janka E, Kollár S, Hegedűs C, et al. Ultraviolet radiation-mediated development of cutaneous melanoma: an update. J Photochem Photobiol B 2018; 185:169–175.
41. Mouret S, Forestier A, Douki T. The specificity of UVA-induced DNA damage in human melanocytes. Photochem Photobiol Sci 2012; 11:155–162.
42. Premi S, Brash DE. Chemical excitation of electrons: a dark path to melanoma. DNA Repair (Amst) 2016; 44:169–177.
43. Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, et al. Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 2015; 347:842–847.
44. Murray HC, Maltby VE, Smith DW, Bowden NA. Nucleotide excision repair deficiency in melanoma in response to UVA. Exp Hematol Oncol 2015; 5:6.
45. Budden T, Davey RJ, Vilain RE, Ashton KA, Braye SG, Beveridge NJ, Bowden NA. Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair. Oncotarget 2016; 7:60940–60953.
46. Kvam E, Tyrrell RM. Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation. Carcinogenesis 1997; 18:2379–2384.
47. Kvam E, Tyrrell RM. The role of melanin in the induction of oxidative DNA base damage by ultraviolet A irradiation of DNA or melanoma cells. J Invest Dermatol 1999; 113:209–213.
48. Tadokoro T, Yamaguchi Y, Batzer J, Coelho SG, Zmudzka BZ, Miller SA, et al. Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. J Invest Dermatol 2005; 124:1326–1332.
49. Kamenisch Y, Baban TSA, Schuller W, von Thaler AK, Sinnberg T, Metzler G, et al. UVA-irradiation induces melanoma invasion via the enhanced warburg effect. J Invest Dermatol 2016; 136:1866–1875.
50. Kamenisch Y, Ivanova I, Drexler K, Berneburg M. UVA, metabolism and melanoma: UVA makes melanoma hungry for metastasis. Exp Dermatol 2018; 27:941–949.
51. Zhang H, Rosdahl I. Ultraviolet A and B differently induce intracellular protein expression in human skin melanocytes–a speculation of separate pathways in initiation of melanoma. Carcinogenesis 2003; 24:1929–1934.
52. van Schanke A, Jongsma MJ, Bisschop R, van Venrooij GM, Rebel H, de Gruijl FR. Single UVB overexposure stimulates melanocyte proliferation in murine skin, in contrast to fractionated or UVA-1 exposure. J Invest Dermatol 2005; 124:241–247.
53. Naylor RM, Jeganathan KB, Cao X, van Deursen JM. Nuclear pore protein NUP88 activates anaphase-promoting complex to promote aneuploidy. J Clin Invest 2016; 126:543–559.
54. Terzian T, Torchia EC, Dai D, Robinson SE, Murao K, Stiegmann RA, et al. p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation. Pigment Cell Melanoma Res 2010; 23:781–794.
55. Noonan FP, Zaidi MR, Wolnicka-Glubisz A, Anver MR, Bahn J, Wielgus A, et al. Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment. Nat Commun 2012; 3:884.
56. Setlow RB, Grist E, Thompson K, Woodhead AD. Wavelengths effective in induction of malignant melanoma. Proc Natl Acad Sci U S A 1993; 90:6666–6670.
57. Robinson ES, Hill RH Jr, Kripke ML, Setlow RB. The Monodelphis melanoma model: initial report on large ultraviolet A exposures of suckling young. Photochem Photobiol 2000; 71:743–746.
58. Ley RD. Dose response for ultraviolet radiation A-induced focal melanocytic hyperplasia and nonmelanoma skin tumors in Monodelphis domestica. Photochem Photobiol 2001; 73:20–23.
59. Mitchell DL, Fernandez AA, Nairn RS, Garcia R, Paniker L, Trono D, et al. Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model. Proc Natl Acad Sci U S A 2010; 107:9329–9334.
60. Clough-Gorr KM, Titus-Ernstoff L, Perry AE, Spencer SK, Ernstoff MS. Exposure to sunlamps, tanning beds, and melanoma risk. Cancer Causes Control 2008; 19:659–669.
61. de Vries E, Arnold M, Altsitsiadis E, Trakatelli M, Hinrichs B, Stockfleth E, et al. Potential impact of interventions resulting in reduced exposure to ultraviolet (UV) radiation (UVA and UVB) on skin cancer incidence in four European countries, 2010–2050. Br J Dermatol 2012; 167 (Suppl 2):53–62.
62. El Ghissassi F, Baan R, Straif K, Grosse Y, Secretan B, Bouvard V, et al.; WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens–part D: radiation. Lancet Oncol 2009; 10:751–752.
63. Rodriguez-Acevedo AJ, Green AC, Sinclair C, van Deventer E, Gordon LG. Indoor tanning prevalence after the International Agency for Research on Cancer statement on carcinogenicity of artificial tanning devices: systematic review and meta-analysis. Br J Dermatol 2020; 182:849–859.
64. Boniol M, Autier P, Boyle P, Gandini S. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ 2012; 345:e4757.
65. Colantonio S, Bracken MB, Beecker J. The association of indoor tanning and melanoma in adults: systematic review and meta-analysis. J Am Acad Dermatol 2014; 70:847–57.e1.
66. O’Sullivan DE, Brenner DR, Demers PA, Villeneuve PJ, Friedenreich CM, King WD; ComPARe Study Group. Indoor tanning and skin cancer in Canada: a meta-analysis and attributable burden estimation. Cancer Epidemiol 2019; 59:1–7.
67. An S, Kim K, Moon S, Ko KP, Kim I, Lee JE, Park SK. Indoor tanning and the risk of overall and early-onset melanoma and non-melanoma skin cancer: systematic review and meta-analysis. Cancers (Basel) 2021; 13:5940.
68. Burgard B, Schöpe J, Holzschuh I, Schiekofer C, Reichrath S, Stefan W, et al. Solarium use and risk for malignant melanoma: meta-analysis and evidence-based medicine systematic review. Anticancer Res 2018; 38:1187–1199.
69. Lazovich D, Vogel RI, Berwick M, Weinstock MA, Anderson KE, Warshaw EM. Indoor tanning and risk of melanoma: a case-control study in a highly exposed population. Cancer Epidemiol Biomarkers Prev 2010; 19:1557–1568.
70. Suppa M, Gandini S, Njimi H, Bulliard JL, Correia O, Duarte AF, et al.; Euromelanoma Working Group,. Association of sunbed use with skin cancer risk factors in Europe: an investigation within the Euromelanoma skin cancer prevention campaign. J Eur Acad Dermatol Venereol 2019; 33 (Suppl 2):76–88.
71. Ghiasvand R, Rueegg CS, Weiderpass E, Green AC, Lund E, Veierød MB. Indoor tanning and melanoma risk: long-term evidence from a prospective population-based cohort study. Am J Epidemiol 2017; 185:147–156.
72. Karapetyan L, Yang X, Wang H, Sander CA, Moyer A, Wilson M, et al. Indoor tanning exposure in association with multiple primary melanoma. Cancer 2021; 127:560–568.
73. Stern RS, Nichols KT, Väkevä LH. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med 1997; 336:1041–1045.
74. Stern RS; PUVA Follow-up Study. The risk of melanoma in association with long-term exposure to PUVA. J Am Acad Dermatol 2001; 44:755–761.
75. Hannuksela-Svahn A, Sigurgeirsson B, Pukkala E, Lindelöf B, Berne B, Hannuksela M, et al. Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis. Br J Dermatol 1999; 141:497–501.
76. Lindelöf B, Sigurgeirsson B, Tegner E, Larkö O, Johannesson A, Berne B, et al. PUVA and cancer risk: the Swedish follow-up study. Br J Dermatol 1999; 141:108–112.
77. Longo MI, Bulliard JL, Correia O, Maier H, Magnússon SM, Konno P, et al. Sunbed use legislation in Europe: assessment of current status. J Eur Acad Dermatol Venereol 2019; 33 (Suppl 2):89–96.
78. AIM at Melanoma Foundation. Indoor Tanning Legislation 2022 [Internet]. [cited 2022 Aug 4]. https://www.aimatmelanoma.org/legislation-policy-advocacy/indoor-tanning/. [Accessed 1 August 2022]
79. FDA, Health and Human Services. Sunscreen Drug Products for Over-the-Counter Human Use [Internet]. Food and Drug Administration; 2019 Feb [cited 2019 Oct 2] p. 72. Report No.: FDA–1978–N–0018. https://www.govinfo.gov/content/pkg/FR-2019-02-26/pdf/2019-03019.pdf. [Accessed 1 October 2019]
80. Guan LL, Lim HW, Mohammad TF. Sunscreens and photoaging: a review of current literature. Am J Clin Dermatol 2021; 22:819–828.
81. Research C for DE and. Questions and Answers: FDA posts deemed final order and proposed order for over-the-counter sunscreen. FDA [Internet]. 2021 Nov 16 [cited 2022 Feb 13]; https://www.fda.gov/drugs/understanding-over-counter-medicines/questions-and-answers-fda-posts-deemed-final-order-and-proposed-order-over-counter-sunscreen
82. Health C for D and R. Tanning [Internet]. FDA. 2019 [cited 2019 Oct 6]. http://www.fda.gov/radiation-emitting-products/radiation-emitting-products-and-procedures/tanning
83. Guy GP Jr, Berkowitz Z, Holman DM, Hartman AM. Recent changes in the prevalence of and factors associated with frequency of indoor tanning among US adults. JAMA Dermatol 2015; 151:1256–1259.
84. Calzavara-Pinton PG, Arisi M, Wolf P. Sunbeds and carcinogenesis: the need for new regulations and restrictions in Europe from the Euromelanoma perspective. J Eur Acad Dermatol Venereol. 2019; 33(Supp 2):104–109.
85. Gordon LG, Hainsworth R, Eden M, Epton T, Lorigan P, Grant M, et al. Sunbed use among 11- to 17-year-olds and estimated number of commercial sunbeds in England with implications for a ‘Buy-Back’ scheme. Children (Basel) 2021; 8:393.
86. Solazzo AL, Geller AC, Hay JL, Ziyadeh NJ, Charlton BM, Frazier AL, Austin SB. Indoor ultraviolet tanning among U.S. adolescents and young adults: results from a prospective study of early onset and persistence. J Adolesc Health 2020; 67:609–611.
87. Gordon LG, Rodriguez-Acevedo AJ, Køster B, Guy GP Jr, Sinclair C, Van Deventer E, Green AC. Association of indoor tanning regulations with health and economic outcomes in North America and Europe. JAMA Dermatol 2020; 156:401–410.
88. Guy GP Jr, Zhang Y, Ekwueme DU, Rim SH, Watson M. The potential impact of reducing indoor tanning on melanoma prevention and treatment costs in the United States: an economic analysis. J Am Acad Dermatol 2017; 76:226–233.
Keywords:

environmental radiation; melanoma; radiation; skin cancer; ultraviolet; ultraviolet A

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