Skin is the most common organ to be affected by cancer in the United States, and the incidence of skin cancer has been rising rapidly over the past several decades, especially among younger adults. The causes of this trend are multi-factorial, but UV exposure patterns are broadly accepted as contributory, as fits the extensive evidence that UV radiation induces DNA damage in the skin, which can initiate carcinogenesis [2
]. In particular, the aromatic heterocyclic bases in DNA absorb strongly in the wavelength range of UVB, leading to the generation of cyclobutane pyrimidine dimers that cause C→T and CC→TT mutations [4
]. Recent evidence suggests that radiation in the UVA range can also trigger DNA damage via cyclobutane pyrimidine dimer formation [5
]. This DNA photodamage can be repaired through mechanisms involving the tumor suppressor p53 (or, in cases of more extensive damage, p53 plays a role in regulating apoptosis), though p53 itself is subject in the skin to dipyrimidine mutagenesis. Thus, UV-mediated DNA damage has carcinogenic potential both by initiating mutations throughout the genome and by contributing to loss of p53 function [6
Importantly, DNA damage also initiates the tanning pathway. When activated in response to DNA damage in keratinocytes, p53 binds to and upregulates transcription of the pro-opiomelanocortin (POMC) gene [8**
] (). The POMC polypeptide is post-translationally cleaved into several products, including α-melanocyte-stimulating hormone, which then signals to melanocytes via the melanocortin 1 receptor (MC1R) [9
]. If signaling through this receptor is disrupted, tanning does not occur, as in red-haired individuals who harbor loss-of-function polymorphisms of MC1R and burn in response to sun exposure without tanning [10
]. In other words, UV-mediated DNA damage can occur in some individuals in the absence of tanning, but tanning does not apparently occur without antecedent DNA damage. These data cast significant doubt over the theoretical possibility of a truly “safe tan.”
Schematic of molecular steps in the tanning and UV-carcinogenesis pathways. DNA damage appears to be a common/proximal intermediate in both pathways.
While sun exposure is a known risk factor for developing skin cancer, particularly squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), comparatively less attention has been directed at indoor tanning as a risk factor. An important study from 2002 addressed this question, finding that indoor tanning does contribute significantly to the risk of developing SCC and BCC [11
]. Based on a sample of 603 BCC patients and 293 SCC patients, along with 540 controls, this study found that ever having used a tanning device resulted in a 50% increase in BCC risk (OR = 1.5, 95% CI = 1.1-2.1) and more than doubled the risk of developing SCC (OR = 2.5, 95% CI = 1.7-3.8). Age at first use of a tanning device was also a significant risk factor, with age less than 20 years associated with the highest risk for both BCC and SCC.
The tanning industry has attempted to downplay the significance of the elevated BCC and SCC risk, arguing that these forms of skin cancer are generally less aggressive than melanoma. Such an argument ignores the fact that non-melanoma skin cancer, especially SCC, does have metastatic potential and is likely responsible for thousands of potentially avoidable deaths each year in the United States [3
]. Additionally, the morbidity associated with surgical excision of non-lethal BCC and SCC and the utilization of healthcare resources to treat these preventable cancers are substantial.
Nonetheless, by shifting the discussion away from BCC and SCC and toward melanoma, the tanning industry has all but invited scientific inquiry into the association between indoor tanning and melanoma risk. Early studies of this association produced equivocal results, perhaps because indoor tanning has gained in popularity only over the past thirty years, and, due to the lag time characteristic of melanoma development, early studies may not have allowed for a sufficiently long post-exposure period to adequately assess melanoma risk. Indeed, a recent case-control study by Clough-Gorr et al produced equivocal results for the same reason; the study found a non-statistically significant increase in melanoma risk for individuals who had ever used a tanning bed (OR = 1.14, 95% CI = 0.80-1.61), but their study population had, on average, only begun using tanning beds 17 years prior to the time of data collection, which corresponded to a later age at first use [12*
]. By contrast, a recent report by Ting et al enrolled a slightly younger population, composed of 1518 dermatologic patients, among whom there were 79 cases of malignant melanoma [13*
]. This study found that ever using a tanning bed was associated with an increased risk of developing malignant melanoma (OR = 1.64, 95% CI = 1.01-2.67), and, importantly, this risk was particularly pronounced among women aged 45 years or younger (OR = 3.22, 95% CI = 1.01-11.46).
A landmark study published in 2007 by the International Agency for Research on Cancer confirms the association between indoor tanning and melanoma [14**
]. The authors conducted a meta-analysis of all 19 reports published to that time that evaluated indoor tanning behavior and malignant melanoma risk. The included reports represented a total of 7,355 cases across 3 continents and spanned 24 years of publication. In total, having ever used a tanning bed was associated with an increased risk of melanoma (summary RR = 1.15, 95% CI = 1.00-1.31). Out of the 19 reports initially included in the meta-analysis, 7 contained data on age at first use of a tanning bed. Based on those 7 studies, first exposure to indoor tanning before age 35 years was associated with a 75% increased risk of developing melanoma (summary RR = 1.75, 95% CI = 1.35-2.26), as shown in .
Figure 2 Relative risk of melanoma associated with early first exposure to indoor tanning: estimates of 7 studies and summary estimate. Reprinted with permission [14**].
Importantly, numerous laboratory models suggest that relatively low-dose UV exposure, which would not be sufficient to generate erythema (“sunburn”), is still able to induce skin carcinogenesis [15*
]. Thus, the notion of “responsible tanning” is, together with “safe tanning” mechanistically incongruous since the ability to induce measurable tanning shares a carcinogenic intermediate.