The Road to Group I

How the International Agency for Research on Cancer Came to Classify Indoor Ultraviolet (UV) Tanning as Carcinogenic to Humans
Philippe Autier, MD, MPH

TanningBedFace_Jrnl10pg68In 2009, a working group of the International Agency for Research on Cancer (IARC), affiliated with the World Health Organization (WHO), added ultraviolet radiation (UVR) from tanning machines to its Group I list of the most carcinogenic (cancer-causing) forms of radiation. Citing evidence from years of international research on the relationship between indoor tanning and skin cancer, the IARC placed this type of UVR in a danger category alongside offenders such as radon, plutonium, and solar UVR.

UVB and Skin Cancer
Visible_UV_Jrnl10pg68_300wAn estimated 90 percent of all skin cancers are associated with exposure to UV radiation, mainly from the sun. UV reaches the earth in the form of shortwave, ultraviolet B (UVB) and long-wave, ultraviolet A (UVA) rays. Scientists have been studying UVR for decades, and by the end of the 1980s 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 what resembled human squamous cell carcinoma (the second most common human skin cancer) 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, the risk of which was then strongly associated with a history of sunburn. Thus, UVB was believed to be the major cause of skin cancer. Much less data was available on the role of UVA in skin cancer. However, 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 a thorough review of all available data from laboratory, animal, and human studies, in 1992 a Working Group convened by the IARC first placed solar radiation, and more specifically the sun's UV radiation, in the IARC Group I of the most dangerous carcinogenic agents for humans.1 (For details on the criteria for Group I, see - monograph program.) However, there wasn't yet sufficient evidence to assign specific wavelengths, like UVB, to Group I, so both UVA and UVB were classified as "probably carcinogenic to humans," placing them in the IARC's Group IIa. Evidence suggested but was not yet conclusive that UVB was a human carcinogen, and UVA was suspected to be a carcinogen.

Uncertainties primarily resulted from the many unanswered questions about the causes of melanoma, the deadliest form of skin cancer. In animal studies, UVB was found to induce squamous cell carcinoma (SCC), but had not been found to cause tumors resembling human melanomas; nor had DNA mutations specific to UVB exposure been found in melanoma. Epidemiologic studies (statistical studies on human populations that explore the links between human health effects and specified causes) suggested that melanoma was due to 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,squamous cell carcinoma 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 did not appear as clear or important as it was in squamous cell carcinoma. 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 - also was emitted, since this wavelength is better at inducing a deep, long-lasting tan.) 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. 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 UVA exposure from indoor tanning and skin cancer, especially melanomas of the skin and eyes. These data were systematically reviewed in an IARC monograph in June 2009, and the main results can be summarized as follows:

1. Extensive laboratory data and animal experiments document a role for UVA in skin cancer development.2,3 In fact, UVA penetrates the skin more deeply than UVB and can cause damage to cells in the middle layer of skin (the dermis), while UVB does most of its damage in the top layer (epidermis). UVB causes DNA mutations more directly, while UVA causes DNA damage more indirectly; however, in both cases the DNA mutations can lead to cancer. And there is some evidence that the body's repair and removal of damaged DNA is less effective when the damage is caused by UVA.

2. Experiments in human volunteers show that tanning lamps produce the types of DNA damage associated with UV-induced skin cell mutations that can lead to cancer.4

3. Experiments in human volunteers also show that both UVA and UVB can damage the immune system.4

4. Systematic reviews of studies show that intermittent, intense sun exposure is the main environmental risk factor for melanoma5; this pattern can be simulated by indoor UV tanning.

Figure 1. Risk of Melanoma in People <35 Years Old at First Sunbed Use4,6
Figure 1: A 2006 survey (meta-analysis) of key tanning bed studies over the past two decades found an overall 75 percent increase in melanoma 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.] Summary relative risk indicates the total range of relative risk, from 1.35 - 2.26.

5. While studies have not consistently shown that indoor UV tanning is a risk factor for melanoma, during a 2006 IARC review, all seven studies examined found a significant increase in melanoma risk (ranging from a 40 percent increase to a 228 percent increase) when indoor UV tanning started during adolescence or young adulthood.4,6 The meta-analysis (an analysis of the results of several studies) found an overall 75 percent increase in melanoma risk when indoor UV tanning began before tanners reached 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.7

6. Four studies have reported an increased risk for ocular melanoma among UV tanning device users.8 Again, the risk of this rare but dangerous cancer was greater for subjects who started indoor tanning before age 20.

Further review of the studies by the IARC found no indication that the findings were due to any problems with study design. All the research substantiated a role for both UVA and UVB in human cancer development. Thus, the entire UV spectrum and UV-emitting tanning devices were classified as carcinogenic to humans.9

UV tanning's relationship to the rise in melanoma incidence has been corroborated by a number of recent epidemiological studies. 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.10 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.11,12 [See Figure 2].

Figure 2. Melanoma in Sweden, 1960-200411
Figure2A_Jrnl10pg70_300w Figure2B_Jrnl10pg70_300w
Figure 2. 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.

DR. AUTIER is the Research Director of the iPRI (International Prevention Research Institute), in Lyon, France, and the former Head of the Unit of Prevention Evaluation and Cluster Coordinator of the Biostatistics and Epidemiology Cluster at the International Agency for Research on Cancer (IARC), affiliated with the World Health Organization (WHO).

Dr. Autier is a member of the editorial board of Melanoma Research and the European Journal of Cancer and a member and co-chairman of EPIMEL, the Epidemiology and Prevention section of the EORTC Melanoma Cooperative Group. He has published more than 140 scientific articles.

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