Carcinogenic to Humans: Why the International Agency for Research on Cancer Added Indoor Ultraviolet (UV) Tanning to Group I


Philippe Autier, MD, MPH
Research Director
International Prevention
Research Institute, Lyon, France
Former Head
Unit of Prevention Evaluation
International Agency for
Research on Cancer, Affiliated with the World Health Organization
 
In 2009, a working group of 20 scientists from around the world, brought together by the International Agency for Research on Cancer (IARC), added ultraviolet radiation (UVR) from tanning machines to the IARC’s Group I list of the most carcinogenic forms of radiation.1 Citing evidence from years of international research on the relationship between indoor tanning and skin cancer, the IARC, affiliated with the World Health Organization, placed this type of UVR in its most dangerous cancer category for humans, alongside offenders such as radon, asbestos, cigarettes, plutonium, and solar UVR.
 
UVB and Skin Cancer
An estimated 90 percent of all skin cancers are associated with exposure to UV radiation, above all from the sun, reaching the earth as shortwave, ultraviolet B (UVB) and long-wave, ultraviolet A rays (280 to 315 nm and 315 to 400 nm, respectively). UVB composes about 5 to 10 percent and UVA 90 to 95 percent of the UVR to which we are exposed. By the end of the 1980s, after decades of study, scientists had well documented the carcinogenic properties of UVB. They knew that in the lab, it caused DNA mutations in skin cells that led to the development of cancer; triggered the growth of squamous cell carcinomas in rodents; and was more responsible than UVA for inducing sunburn. At the same time, studies provided increasing evidence that sunlight was the main environmental cause of skin cancer, which at that time was strongly associated with a history of sunburn. Thus, UVB was believed to be the major cause of skin cancer. Far less information was available on the role of UVA in skin cancer, but scientists considered it of the utmost importance to learn more, believing that research could prompt innovations in sun protection, such as improved, broader spectrum sunscreen formulations.
                                 
After thorough review of all available data from laboratory, animal, and human studies, in 1992 a Working Group convened by the IARC determined that sufficient evidence existed to place solar radiation, and more specifically solar UVR, in the IARC’s Group I – the most dangerous carcinogenic agents for humans.2 (For details on the criteria for Group I, see www.iarc.fr, monograph program.) However, there wasn’t yet sufficient evidence to assign specific wavelength ranges, like UVB, to Group I – evidence suggested but was not yet conclusive that UVB was a human carcinogen, and UVA was suspected to be a carcinogen – so both were classified as “probably carcinogenic to humans,” placing them in the IARC’s group IIa.
 
Uncertainties primarily stemmed from the many unanswered questions about the environmental causes of melanoma. In animal studies, UVB was found to induce squamous cell carcinoma (SCC), but had not yet been found to cause tumors akin to human melanomas; nor had DNA mutations specific to UVB exposure been found in melanoma. Epidemiologic studies suggested that melanoma was primarily caused by intermittent, intense sun exposure, acquired mainly during tanning, leisure, or sports activities. This would explain why melanoma was frequently found on areas normally sun-protected in everyday life, such as the trunk and thighs. In contrast, SCC occurred most frequently on chronically sun-exposed areas (e.g., the head and neck) of elderly subjects, and was considered to be mainly due to cumulative sun exposure. At that point, the involvement of sun exposure, and of UVB in particular, in the development of melanoma simply was not as clear as it was in SCC. With even less known about UVA, it was deemed premature to make a clear-cut distinction between UVB’s and UVA’s roles in skin cancer.
 
The Role of UVA
The marketing of modern UV tanning devices started at the end of the 1980s, with the advent of fluorescent lamps mainly emitting UVA rays. (Some UVB — less than five percent of the lamps’ UV output — was also emitted, since this wavelength is better at inducing a deep, long-lasting tan; UVA induces tanning quickly, while a UVB tan may take some days to develop, but stays dark longer.) With no convincing proof yet of UVA’s link to skin cancer and only a low amount of UVB included, tanning vendors could argue that acquiring a tan was safe (or safer) when obtained at a salon.
                                            
During the 1990s and into the 2000s, indoor tanning became very popular among light-skinned populations, and is now suspected to be one cause of the rise in melanoma incidence; nearly 30 million people tan indoors every year in the US alone,3 about 2.3 million of them teens,4 and melanoma is now the most common form of cancer for young adults 25-29 years old and the second most common for adolescents and young adults 15-29 years old.5 Powerful UV tanning units may be 10 to 15 times stronger than the midday sunlight on the Mediterranean Sea, subjecting indoor tanners to UVA doses well above those experienced during daily life or even when sunbathing outdoors. The fact is, repeated exposure to large, concentrated amounts of UVA constitutes a new experience for human beings.
 
Studies have gradually strengthened the evidence for a causal relationship between high doses of UVA exposure, indoor tanning, and skin cancer, especially melanomas of the skin and eyes. These data were systematically reviewed in an IARC monograph in June 2009,1 and the main results can be summarized as follows:
 
1.    Extensive laboratory data and animal experiments (on DNA mutations and repair, immune function, cell integrity, cell cycle regulation, and other critical biological functions) document a role for UVA in skin carcinogenesis.6,7 The studies show that the carcinogenic mechanisms of UVB differ but sometimes overlap with those of UVA. Exposure to the sun causes a specific mutation pattern – cytidine to thymidine transition — due to cyclobutane pyrimidine dimers in DNA, and UVB was long assumed to be the culprit. But the same transition pattern has now been found in the skin of UVA-exposed mice, the Tp53 gene of UVA- or UVB-induced skin tumors in hairless mice, and the TP53 gene in human actinic keratosis and malignant skin tumors.1,6 UVA actually penetrates the skin more deeply than UVB and can damage cells (including melanocytes) in the dermis, while UVB does most of its damage in the epidermis. UVB causes DNA mutations directly, and UVA more indirectly, producing free radicals and reactive oxygen species, such as hydroxyl and oxygen radicals, which then damage DNA in the skin cells. In either case, the mutations can lead to cancer. Recent evidence also shows that the body’s repair and removal of damaged DNA is less effective when the damage is caused by UVA.8
     
2.   Experiments in human volunteers show that tanning lamps produce the types of skin DNA damage associated with photocarcinogenesis.9
 
3.    Experiments in human volunteers also show that UVA and UVB can weaken the immune system through interacting and overlapping mechanisms, increasing vulnerability to cancer as well as other diseases.9
 
4.   Systematic reviews of epidemiological studies provide strong evidence that intermittent, intense sun exposure – the type of exposure often sustained on weekends or sunny vacations, leading to sunburn – is the main environmental risk factor for melanoma;10 this pattern can be simulated by indoor UV tanning, and has a greater potential to cause melanomas at younger ages than chronic sun exposure.11
 
5.   While epidemiological studies have not consistently shown that indoor UV tanning is a risk factor for cutaneous melanoma, in a 2006 IARC meta-analysis, all seven studies examined (six case-control and one cohort) found a significant increase in melanoma risk (ranging from a 40 to a 228 percent increase) when indoor UV tanning started during adolescence or young adulthood.9,12 The meta-analysis found an overall 75 percent increase in melanoma risk when indoor UV tanning began before age 35 [Figure 1]. In another meta-analysis, the Working Group found some evidence that UV tanning increased the risk of squamous cell carcinoma, especially when tanning bed use started before age 20. These results were highly consistent with the considerable data pointing to childhood and adolescence as the key periods for initiation and development of melanoma in adulthood.13
 
6.   Four case-control studies have reported consistently increased risk for ocular melanoma among UV tanning device users,14 with a clear dose-response relationship – increased risk with increased indoor tanning. Again, the risk of this rare but dangerous cancer was greater for subjects who started indoor tanning before age 20.
 
 
Figure 1: Risk of Melanoma in People <35 Years Old at First Sunbed Use9,12  
 
A 2006 survey (meta-analysis) of key tanning bed studies over the past two decades found an overall 75 percent increase in melanoma risk when indoor tanning began before tanners reached age 35. [The size of the box on each line (each line repesenting a different study) is proportional to the number of the subjects included in each study.]
 
 
Further review of the studies by the IARC found no indication that the findings were due to biased or otherwise problematic study design. No evidence supported a protective effect from sun bed use against future sun damage,9,12 and all the research substantiated a role for both UVA and UVB in human carcinogenesis. Thus, the entire UV spectrum and UV-emitting tanning devices were classified as carcinogenic to humans.1
 
UV tanning’s role in the rise in melanoma incidence has been corroborated by a number of recent epidemiological observations. A few years ago, we predicted that we would begin seeing an increase in melanomas associated with tanning bed use on the trunk, especially in women.15 In areas where indoor UV tanning is popular, especially among teenagers and young adults, such as in Sweden, Iceland, and Northern Ireland, sharp increases in the incidence of melanoma on the trunk have indeed been described.16, 17,18 [See Figure 2].
 
 
Figure 2: Melanoma in Sweden, 1960-200416  
2A=Men; 2B=Women
 
Incidence (cases/100,000, European Standard Population) of melanoma by body site, men and women, Sweden 1960-2004. While leg melanomas have always predominated in light-skinned women, after 1975 incidence rates for women increased more rapidly on the trunk than on the legs, and by the end of the 1990s, the incidence of trunk melanomas had caught up to that of leg melanomas. Experts hypothesize that this phenomenon among women is largely due to increased full-body exposure to tanning devices.
 
 
In view of all the amassed knowledge on the detrimental effects of indoor UV tanning, public health officials need to increase control over indoor tanning, starting by preventing exposure to UV lamps by teenagers and young adults.
                                            
References
1.   El Ghissassi F, Bann R, Starif K, et al. A review of human carcinogens – Part D: radiation. Lancet Oncol 2009; 10(8):751-752.
2.   International Agency for Research on Cancer (IARC). Solar and ultraviolet radiation. Monographs on the Evaluation of Carcinogenic Risks to Humans. No. 55. Lyon: International Agency for Research on Cancer; 1992.
3.  Kwon HT, Mayer JA, Walker KK, Yu H, Lewis EC, Belch GE. Promotion of frequent tanning sessions by indoor tanning facilities: two studies. J Am Acad Dermatol 2003; 46:700-5.
4.  Demierre MF. Time for the national legislation of indoor tanning to protect minors. Arch Dermatol 2006; 139:520-4.
5.  Swerdlow AJ, Weinstock MA. Do tanning lamps cause melanoma? An epidemiologic assessment. J Am Acad Dermatol 1998; 39:89-98.
6.  Rünger TM, Kappes UP. Mechanisms of mutation formation with long-wave ultraviolet light (UVA). Photodermatology, Photoimmunology & Photomedicine 2008; 24:2–10.7.
7.  Ridley AJ, Whiteside JR, McMillan TJ, et al. Cellular and subcellular responses to UVA in relation to carcinogenesis. Int J Radiat Biol 2009; 85:177-195.
8. Mouret S, Baudouin C, Charveron M, Favier A, Cadet J, Douki T. Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proc Natl Acad Sci U S A 2006; 103:13765-70.
9.  International Agency for Research on Cancer (IARC). Exposure to artificial UV radiation and skin cancer. IARC Working Group Reports No 1. IARC, Lyon; 2006 (available free at www.iarc.fr).
10.       Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer 2005; 41:45–60.
11.       Autier P, Severi G, Boniol M, de Vries E, Coebergh J-W, Dore JF. Correspondence: Re: Sun exposure and mortality from melanoma. JNCI 2005; 97(15):1159;doi:10.1093/jnci/dji212.
12. 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 Cancer 2007; 120(5):1116-1122. Erratum in: Int J Cancer. 2007; 120(11):2526.
13.       Autier P. Boyle P. Artificial ultraviolet sources and skin cancers: rationale for restricting access to sunbed use before 18 years of age. Nat Clin Pract Oncol 2008; 5(4):178-179.
14.       Vajdic CM, Kricker A, Giblin M, et al. Artificial ultraviolet radiation and ocular melanoma in Australia. Int J Cancer 2004; 112:896-900. PM:15386378.
15. Boniol M, Autier P, Doré JF. Re: A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst 2004; 96(4):335-336.
16. Dal H, Boldemann C, Lindelöf B. Does relative melanoma distribution by body site 1960-2004 reflect changes in intermittent exposure and intentional tanning in the Swedish population? Eur J Dermatol 2007; 17(5):428-434.
17. Montella A, Gavin A, Middleton R, Autier P, Boniol M. Cutaneous melanoma mortality starting to change: A study of trends in Northern Ireland. Eur J Cancer 2009; 45(13):2360-6.

18.       Héry C, Tryggvadóttir L, Sigurdsson T. A melanoma epidemic in Iceland: possible influence of sunbed use. Am J Epidemiology (2010, in press).