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Reviews on sun exposure and artificial light and melanoma
Progress in Biophysics and Molecular Biology 107 (2011) 362e366
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Review
Reviews on sun exposure and artificial light and melanoma Sara Gandinia, *, Philippe Autierb, Mathieu Boniolb a b
European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy International Prevention Research Institute, 95 Cours Lafayette, 69006 Lyon, France
a r t i c l e i n f o
a b s t r a c t
Article history: Available online 19 September 2011
Melanoma is the most common form of cancer among young adults aged 25e29 years and the second most common cancer in those aged 15e29 years. We reviewed all the evidence regarding risk factors for melanoma, looking in particular at childhood exposure to ultraviolet radiation (UV). UV radiation is clearly the predominant environmental and thus potentially modifiable risk factor for melanoma. All activities related to tan-seeking behaviour and history of sunburns were shown to be significantly associated to melanoma. Host factors, such as pigmentary characteristics, and genetic predisposition plays also an important role. UV exposure is not only due to the sun but also to indoor tanning devices that have been shown to lead to an elevated risk of melanoma. The strongest evidence for a link between artificial UV and melanoma is found among individuals who had their first exposure to indoor tanning before the age of 30: they have a 75% increase risk of developing melanoma than individuals who had no exposure to indoor tanning. Prevention is very important, especially for children and young adults, as childhood and adolescence are critical periods in the development of later melanoma. Indoor tanning is a widespread practice in most developed countries, particularly in Northern Europe and the USA. In the recent decades more and more people, especially teenagers and women, are exposed to substantially high radiant exposures of UV through artificial sources and these trends raised a considerable concern. In fact the International Agency for Research on Cancer concluded that the association between skin cancer and exposure to solar radiation and the use of UV-emitting tanning devices are causal. Interesting analyses carried out in Iceland showed that when interventions to discourage sunbed use were introduced the incidence of melanoma among women decreased. All this evidence encouraged many countries to introduce regulations on sunbed use to avoid exposure before the age of 18. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Ultraviolet radiation Indoor tanning Sun Melanoma
Contents 1. 2. 3. 4. 5. 6.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 Melanoma risk factors: phenotypic and genetic factors, sun exposure and childhood susceptibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Sun exposure, vitamin D and cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Indoor tanning and skin cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 Prevalence of exposure to artificial UV for tanning purposes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
1. Introduction
* Corresponding author. E-mail address: [email protected] (S. Gandini). 0079-6107/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.pbiomolbio.2011.09.011
Over the last 25 years, cutaneous melanoma (CM) has become an increasingly common cause of cancer morbidity and mortality in
S. Gandini et al. / Progress in Biophysics and Molecular Biology 107 (2011) 362e366
Caucasian populations worldwide (Berwick et al., 2005; de Vries et al., 2003). The incidence rates of melanoma have also increased significantly in the last decade (Garbe and Leiter, 2009). The incidence of melanoma and non-melanoma skin cancer (NMSC) is increasing at a rapid rate, particularly among young women. Melanoma is the most common form of cancer among young adults aged 25e29 years and the second most common cancer in those aged 15e29 years (Christenson et al., 2005; Birch-Johansen et al., 2010). In this paper we reviewed all the evidence regarding all known risk factors for melanoma, looking in particular at childhood exposure to ultraviolet radiation (UV). Although much remains to be learned about the type, periodicity, and timing of sun exposure, UV radiation is clearly the predominant environmental and thus potentially modifiable risk factor for melanoma. Prevention is supremely important, especially for children and young adults, as childhood and adolescence are critical periods in the development of later melanoma. However UV exposure is not only due to the Sun but also to indoor tanning devices that have been shown to lead to an elevated risk of melanoma, especially in young adults (International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer, 2007). The modifying effect of host and genotypic factors has also been studied in many populations. Even if it is important to remember that sunlight is the most common source of vitamin D which has potential anti-carcinogenic properties, all types of UV radiation were classified by the International Agency for Research on Cancer (IARC) “carcinogenic to humans” (Group 1). The IARC concluded that the association between skin cancer and exposure to solar radiation and the use of UV-emitting tanning devices are causal (El Ghissassi et al., 2009). 2. Melanoma risk factors: phenotypic and genetic factors, sun exposure and childhood susceptibility Although solar UV exposure is the major established environmental risk factor for cutaneous malignant melanoma, the association is complex. In a meta-analysis summarising 57 studies on sun exposure and melanoma, we showed that intermittent sun exposures, such as all activities related to tan-seeking behaviour, and history of sunburns, a marker of intermittent exposure, substantially double the melanoma risk: Summary Relative Risk (SRR) ¼ 1.61 with 95% Confidential Interval (CI): (1.31, 1.99), and SRR: 2.03, with 95% CI: (1.73, 2.37) for intermittent sun exposure and sunburns respectively (Gandini et al., 2005a). Host factors are also important, with number of naevi which is associated to sun exposure, being the most powerful predictor of melanoma risk (Gandini et al., 2005b). In a meta-analysis on 47 studies we observed that number of common naevi, that is associated to sun exposure, is a key factor with a substantially increased risk associated 7 fold greater with the presence of 101e120 naevi compared with <15 naevi: SRR ¼ 6.89 (95% CI: 4.63, 10.25). Similar estimates were obtained for atypical naevi: SRR ¼ 6.36 (95% CI: 3.80, 10.33; for 5 versus 0 atypical naevi). Pigmentary characteristics such as hair, eye and skin colour and Fitzpatrick classification of skin’s sensitivity to sunburns and ability to tan, together with family history and actinic damage indicators, also determine melanoma susceptibility (Gandini et al., 2005c). Genetic predisposition plays also an important role. Hair colour is a phenotypic indicator of the Melanocortin-1-receptor (MC1R) genotype that may modify the association between naevi and melanoma risk. MC1R is one of the major genes that determine skin pigmentation. We performed a meta-analysis on the association between the MC1R variants and melanoma and/or red hair, fair skin phenotype. This meta-analysis provided evidence that some MC1R
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variants are associated both with melanoma and phenotype, while other are only associated with melanoma development. These results suggest that MC1R variants could play a role in melanoma development both via pigmentary and non-pigmentary pathways (Fargnoli et al., 2010). A meta-analysis was performed to evaluate if CM risk factors differ depending on CM body site (Caini et al., 2009). High naevus counts are strongly associated with CM on usually not sun exposed body sites (P < 0.001) confirming that individuals with a high propensity for melanocyte proliferation tend to develop melanomas on intermittently sun exposed body sites. These results were in agreement with the hypothesis of different pathways for melanoma: one related to melanocytes instability and intermittent sun exposure and the other that required long sun exposure (Green, 1992; Whiteman et al., 2003; Whiteman, 2010). Migrant studies provide convincing evidence of childhood and adolescence being critical periods for the development of a later melanoma. They suggest that adults are at increased melanoma risk if they spent childhood in sunny geographical locations or generally received intermittent sun exposure during vacation and/or recreation. In an Australian case-control study published in 1984 (Holman and Armstrong, 1984a,b; Holman et al., 1986; English and Armstrong, 1988) age at arrival and duration of residence in Australia was studied. Earlier age at arrival was a predictor of melanoma risk with little residual effect of duration of residence. Specifically, migrants arriving before age 10 years appeared to have a risk similar to that of native born Australians, whereas the estimated incidence in those arriving after age 15 years was around one quarter of the native born rate, with arrival at later ages giving no additional advantage. Similarly, in an European case-control study, age <10 years old at arrival in a sunny location of residence (that is, the Mediterranean, subtropics, or tropics) conferred a fourfold increased risk of developing melanoma (Autier et al., 1997). In addition to migrant studies, location of residence studies provide further evidence that sun exposure in childhood and adolescence is closely associated with melanoma risk. A nested case-control analysis from the Nurses’ Health Study cohort (Weinstock et al., 1989) showed an increased risk of melanoma in women whose residence during the ages 15e20 years was more equatorial in latitude whereas latitude of residence after 30 years of age was not significantly related to melanoma risk. In another study of 474 cases and 926 controls, those who lived near the coast before the age of 15 years had an increased risk of melanoma compared to those who never lived near the coast (OR ¼ 1.6; 95% CI 1.0e2.6) (Osterlind et al., 1988). 3. Sun exposure, vitamin D and cancer Worldwide photosynthesis from sunlight is the most common source of vitamin D. 25-hydroxyvitamin D (25OHD), which is the main circulating and storage form of Vitamin D, undergoes 1ahydroxylation in the kidney to form the active hormone, 1,25dihyroxyvitamin D. 1,25-dihyroxyvitamin D was shown to be an anti-proliferative, pro-differentiation and pro-apoptotic agent (Osborne and Hutchinson, 2002; Deeb et al., 2007). We performed a meta-analysis of observational studies of serum 25-hydroxyvitamin D level and colorectal, breast and prostate cancer. Because in caseecontrol studies, serum 25-hydroxyvitamin D level is measured after the diagnosis of cancer, separate analyses for caseecontrol and prospective studies were done. The analysis of 35 independent studies showed that 10 ng/ml increase in serum 25-hydroxyvitamin D was associated to a significant decreased risk for colorectal cancer: SRR ¼ 0.85 (95% CI: 0.79, 0.91). For breast
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cancer caseecontrol studies had major limitations and we concluded that the association with breast and prostate cancer were not convincing (Gandini et al., 2011). The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. We performed a meta-analysis on the association between the two most studied VDR polymorphisms (FokI and BsmI) and any cancer site. Results showed that the two polymorphisms might modulate the risk of cancer of skin, breast, and prostate and possibly affect cancer risk at any site in Caucasians (Gandini et al., 2009; Raimondi et al., 2009). 4. Indoor tanning and skin cancer For most individuals, the main source of exposure to ultraviolet radiation is the sun. Nevertheless, some individuals are exposed to substantially high doses of UV through artificial sources. Sunbeds and sunlamps used for tanning purposes are the major source of deliberate exposure to UV radiations. In 2007 we published a meta-analysis summarising twentythree observational studies (22 caseecontrol, one cohort) that investigated the association between indoor tanning use and risk for melanoma, and 7 caseecontrol studies for keratinocytic skin cancers. Among the 19 informative studies, the summary relative risk estimate forever versus never use of indoor tanning was 1.14 (95% CI: 1.00, 1.31). When the analysis was restricted to the nine population-based caseecontrol studies and the cohort study, the SRR was 1.18 (95% CI: 0.97, 1.43). All studies that examined age at first exposure found an increased risk for melanoma when exposure started before approximately 30 years of age, with a summary relative risk estimate of 1.75 (95% CI: 1.35, 2.26). Studies on exposure to indoor tanning and squamous cell carcinoma found some evidence for an increased risk for squamous cell carcinoma. Studies on basal cell carcinoma did not support an association with use of indoor tanning facilities (International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer, 2007). Given the estimates of the meta-analysis Hirst et al. (2009) estimated the numbers of potential skin cancers prevented through regulation of solaria and the associated cost-savings to the Federal Government. The results was that with stricter regulations, between 18 and 31 melanomas, 200e251 squamous cell carcinomas and associated costs of $AU 256,054 would be avoided per 100,000 persons. In the previous meta-analysis we were not able to carry out a doseeresponse meta-analysis because there were not enough published data. Recently some studies published data on trend by time, age and number of sessions. After our meta-analysis, a further big study was published: a caseecontrol study nested within the Nurses’ Health Study. Results showed that sunlamp usage or tanning salon attendance was significantly associated to melanoma after adjusting for potential confounding variables (OR for ‘ever’ versus ‘never’ usage, 2.06, 95% CI: 1.30, 3.26) (Han et al., 2006). In a survey conducted in dermatological clinics in US, women aged 45 years or younger accounted for about 60% of all tanning bed users. In the entire cohort, the “ever-use” of tanning beds was found to be a significant risk factor for the development of melanoma [OR, 1.64; 95% CI: 1.01, 2.67]. The risk was greater in women aged 45 years or younger (OR, 3.22; 95% CI: 1.01, 11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min (OR, 3.18; 95% CI: 1.48, 6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI: 1.41, 12.02) (Ting et al., 2007). Results from the Australian Melanoma Family Study, a multicentre population-based caseecontrol study, confirmed sunbed use
as a risk factor for increasing with greater use, an earlier age at first use and for earlier onset disease: RR ¼ 1.41 (95% CI: 1.01, 1.96) for ever use, and 2.01 (95% CI: 1.22, 3.31) for more than 10 lifetime sessions (P trend 0.01 with cumulative use). The association was stronger for earlier age at first use (P trend 0.02). The association was also stronger for melanoma diagnosed at 18e29 years of age than for melanoma diagnosed at 30e39 years of age: for more than 10 lifetime sessions OR was 6.57 (95% CI: 1.41, 30.49) and 1.60 (95% CI: 0.92, 2.77) for the younger and the older age group respectively (P ¼ 0.01). Among those who had ever used a sunbed and were diagnosed between 18 and 29 years of age, three quarters (76%) of melanomas were attributable to sunbed use (Cust et al., 2011). In a population-based caseecontrol study in UK, those starting sunlamp use at <20 years had an OR ¼ 1.23 (95% CI: 0.81, 1.88) and those starting at >20 years an OR ¼ 1.71 (95% CI: 1.00e2.92). Data suggested increasing risk with number of sunlamp uses and with duration of use (P ¼ 0.02). The OR was 1.96 (95% CI: 1.06e3.61) for having used sunbed and sunlamp (Clough-Gorr et al., 2008). Results from the big prospective cohort study published by Veierod et al. in 2003 were updated with a longer follow-up confirming an increase risk for exposure to indoor tanning. The cohort included 106,366 followed-up from 1991 through 2005 and the RRs increased from 1.24 for rarely use one, two, or three decades from 10 to 39 years to 1.38 for use one or more times per month in one of the three decades to 2.37 for use one or more times per month in two or three decades (P trend ¼ 0.003). The authors found little indication that the relative effects of solarium use varied with hair colour, cutaneous sun sensitivity, or presence of asymmetric large naevi (Veierod et al., 2010). This is further important strong piece of evidence since the statistical power is high and the chance of uncontrolled bias in this big prospective cohort study is very low. Hery et al. (2010) presented a fascinating analysis of an ecologic association of melanoma trends in Iceland. In this study, the authors note a sharp increase in melanoma incidence among young women that began after 1990 with a peak in 2000. At the same time the prevalence of sunbeds in Iceland rapidly increased from 1979 to 1988. They also observed a decline in melanoma rates among women after 2001, following a reduction in prevalence of sunbed use. Despite its reliance on population-level data, this study provides further evidence of causality for sunbed showing that implementation of public health interventions to decrease sunbed use resulted in a concomitant decrease in melanoma rates. 5. Prevalence of exposure to artificial UV for tanning purposes Indoor tanning is a widespread practice in most developed countries, particularly in Northern Europe and the USA. Even in Australia there is growing concern about the expanding solarium industry, particularly among women and young people. Already in 1996 in Canada a survey indicated that a 20% of the adult respondents reported to have used, at least once, a tanning device in a commercial tanning salon during the last 5 years before the survey (Rhainds et al., 1999). In the last decades the prevalence increased: in 2002 in USA a report describing prevalence of indoor tanning use in adults showed an increase prevalence: 38% of adults had ever used indoor tanning facilities (Lazovich et al., 2004). Generally in northern Europe the prevalence is even greater. A caseecontrol study conducted in 1991 in 5 centres in Belgium, France and Germany showed that the proportion of controls that had ever exposed themselves to a sunlamp or a sunbed was higher in Germany (25%) than in Belgium (20%) and in France (6%) (Autier et al., 1994). In a caseecontrol study conducted by the same investigators between 1998 and 2000 in Belgium, France, Sweden (Bataille et al., 2005), the Netherlands and the United Kingdom
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(Autier and Dore, 1998) among persons younger than 50 years (mean age of controls, 37 years), 57% of controls had ever exposed themselves to artificial UV tanning, the highest prevalence of use being found in Sweden (87%) (Bataille et al., 2005). Prevalence in teenagers is worrisome. Two cross-sectional population-based surveys of US youths ages 11e18 years, conducted in 1998 and 2004, showed that the prevalence of indoor tanning use within the past year was around 10%. Half of adolescent indoor tanners in the US used indoor tanning >6 times during the past year and fifty-eight percent of users reported burns from indoor tanning (Cokkinides et al., 2009). In Sweden, according to two studies conducted within the same population in 1988e1990 and in 1995e1997, the prevalence of exposure doubled in 7 years. In 1988e1990, 46% of individuals younger than 30 years had ever exposed themselves to sunlamps or solaria (56% of women and 12% of men, these figures being higher in the 15e24 years age group) while this proportion was only of 24% among individuals older than 30 years (31% of women and 16% of men) (Westerdahl et al., 1994). After 1995, the prevalence of solarium use in the population aged 16e80 years was 41%, but 70% of women and 50% of men aged 18e50 years reported the use of a solarium (Westerdahl et al., 2000). In a survey carried out in USA and published in 2008 the authors found that knowledge of limiting tanning to help prevent melanoma increased from 1988 (25%) to 1994 (77%), but decreased from 1994 to 2007 (67%). This decline in knowledge about limiting tanning was concurrent with an increase in the attitude that having a tan looks better (1994, 69%; 2007, 81%) (Robinson et al., 2008). A survey from USA comparing prevalence by gender indicated that few men and women had used a tanning device before 1980. Women were almost twice as likely as men to report tanning indoors during the 1980s (19% versus 10%), but in the following decades, the proportion of men using indoor tanning facilities approached that of women (15% versus 17% in the 1990s) (Lazovich et al., 2004). Use of indoor tanning facilities is generally more prevalent among women. In 2001, a survey on 12,741 adult volunteers in France (SU.VI.MAX cohort) reported almost three times women having ever experienced indoor tanning than men (22% women and 8% men) (Ezzedine et al., 2008). Cokkinides et al. (2009) showed an increase in the prevalence of past year use of indoor tanning among girls (from 15.6% to 17.7%) and youths ages 14e15 years (from 7.1% to 10.5%). In general younger age (<35 years) is significantly associated with higher likelihood of using indoor tanning facilities among both men and women. In a caseecontrol study comparing data in different European countries (Bataille et al., 2005), exposure before the age of 15 years was reported in 3% of all controls, but reached 20% in Sweden. The mean age at first exposure was 20 years in Sweden, 23 years in the United Kingdom and 27 years in France. Since 1989, a total of 16 studies (18 reports) examined indoor tanning among children and adolescents aged 8e19 years (Lazovich and Forster, 2005; Lazovich et al., 2004). Studies were conducted in Europe (Norway, Sweden and United Kingdom), in various locations throughout the USA (including two nationally representative samples) and in Australia. All these studies showed a frequent use by adolescents and children, sometimes at a very young age. Thirty percent of adolescents in Sweden and 24% of adolescents in the USA aged 13e19 years reported ever use of indoor tanning facilities, and 8% and 12% respectively are frequent users (10 times per year or more). Considering frequency of use, a survey demonstrated that in Scotland 31% of 205 responders had more than five sunbed sessions
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in a year and, for 16% of them, this amounted to over 100 sessions per year (McGinley et al., 1998). In a US survey (Lazovich et al., 2005; Lazovich and Forster, 2005) the median number of times of use was 10 for men and 20 for women, and 21% of women reported frequent use (defined as more than 30 times). A community-based survey was administered in USA to verify if tanning bed operators and patrons are compliant with the US Food and Drug Administration (FDA) exposure limits. In the study published in 2003, out of 483 users 95% were exceeding the recommended exposure times. The average period of tanning for each user was 6.3 weeks (Hornung et al., 2003). 6. Conclusions All activities related to tan-seeking behaviour and history of sunburns were shown to be significantly associated to melanoma. Host factors, such as pigmentary characteristics, and genetic predisposition plays also an important role. Probably individuals with various phenotypes need different pattern of UV exposure to get melanoma. However we have to remember that photosynthesis from sunlight is the most common source of vitamin D that seems to be associated to a reduce risk of several other cancer sites. In the recent decades more and more people, especially teenagers and women, are exposed to substantially high radiant exposures of UV through artificial sources and these trends raised a considerable concern. In fact the International Agency for Research on Cancer (IARC) classified tanning beds and other UVemitting tanning devices as Group 1 carcinogens, meaning that there is sufficient evidence to conclude that these devices cause cancer in humans. The strongest evidence for a link between artificial UV and melanoma is found among individuals who had their first exposure to indoor tanning before the age of 30: they have a 75% increase risk of developing melanoma than individuals who had no exposure to indoor tanning. Hery et al. presented data to suggest that when in Iceland interventions to discourage sunbed use were introduced, the incidence of melanoma among women decreased Hery et al., 2010. All this evidence encouraged many countries to introduce regulations on sunbed use to avoid exposure before the age of 18. Finally in Brazil a government working group was established to review existing legislation, and after extensive discussions with health authorities and the sunbed industry, it was determined that the health benefits of sunbed tanning were little or none, certainly not enough to outweigh their dangers. The Brazilian National Health Surveillance Agency banned UV cosmetic tanning altogether throughout the country (Cumberland and Jurberg, 2009). References Autier, P., Dore, J.F., 1998 08/12. Influence of sun exposures during childhood and during adulthood on melanoma risk. EPIMEL and EORTC melanoma cooperative group. European organisation for research and treatment of cancer. Int. J. Cancer 77 (4), 533e537. Autier, P., Dore, J.F., Lejeune, F., Koelmel, K.F., Geffeler, O., Hille, P., et al., 1994 09/15. Cutaneous malignant melanoma and exposure to sunlamps or sunbeds: an EORTC multicenter case-control study in Belgium, France and Germany. EORTC melanoma cooperative group. Int. J. Cancer 58 (6), 809e813. Autier, P., Dore, J.F., Gefeller, O., Cesarini, J.P., Lejeune, F., Koelmel, K.F., et al., 1997. Melanoma risk and residence in sunny areas. EORTC melanoma co-operative group. European organization for research and treatment of cancer. Br. J. Cancer 76 (11), 1521e1524. Bataille, V., Boniol, M., De Vries, E., Severi, G., Brandberg, Y., Sasieni, P., et al., 2005 Sep. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe. Eur. J. Cancer 41 (14), 2141e2149. Berwick, M., Armstrong, B.K., Ben-Porat, L., Fine, J., Kricker, A., Eberle, C., et al., 2005 02/02. Sun exposure and mortality from melanoma. J. Natl. Cancer Inst. 97 (3), 195e199. Birch-Johansen, F., Jensen, A., Mortensen, L., Olesen, A.B., Kjaer, S.K., 2010 Nov 1. Trends in the incidence of nonmelanoma skin cancer in Denmark 1978e2007: rapid incidence increase among young Danish women. Int. J. Cancer 127 (9), 2190e2198.
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Caini, S., Gandini, S., Sera, F., Raimondi, S., Fargnoli, M.C., Boniol, M., et al., 2009 06/ 20. Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant. Eur. J. Cancer. Christenson, L.J., Borrowman, T.A., Vachon, C.M., Tollefson, M.M., Otley, C.C., Weaver, A.L., et al., 2005 Aug 10. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA 294 (6), 681e690. Clough-Gorr, K.M., Titus-Ernstoff, L., Perry, A.E., Spencer, S.K., Ernstoff, M.S., 2008 Sep. Exposure to sunlamps, tanning beds, and melanoma risk. Cancer Causes Control 19 (7), 659e669. Cokkinides, V., Weinstock, M., Lazovich, D., Ward, E., Thun, M., 2009 Jan 1. Indoor tanning use among adolescents in the US, 1998 to 2004. Cancer 115 (1), 190e198. Cumberland, S., Jurberg, C., 2009 August. From Australia to Brazil: sun worshippers beware. Bull. World Health Organ. 87 (8), 574e575. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC2733274. Cust, A.E., Armstrong, B.K., Goumas, C., Jenkins, M.A., Schmid, H., Hopper, J.L., et al., 2011 May 15. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma. Int. J. Cancer 128 (10), 2425e2435. Deeb, K.K., Trump, D.L., Johnson, C.S., 2007 09. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat. Rev. Cancer 7 (9), 684e700. de Vries, E., Bray, F.I., Coebergh, J.W., Parkin, D.M., 2003 10/20. Changing epidemiology of malignant cutaneous melanoma in Europe 1953e1997: rising trends in incidence and mortality but recent stabilizations in western Europe and decreases in Scandinavia. Int. J. Cancer 107 (1), 119e126. El Ghissassi, F., Baan, R., Straif, K., Grosse, Y., Secretan, B., Bouvard, V., et al., 2009 Aug. A review of human carcinogens e part D: radiation. Lancet Oncol. 10 (8), 751e752. English, D.R., Armstrong, B.K., 1988 05/07. Identifying people at high risk of cutaneous malignant melanoma: results from a case-control study in western Australia. Br. Med. J. (Clin. Res. Ed.) 296 (6632), 1285e1288. Ezzedine, K., Malvy, D., Mauger, E., Nageotte, O., Galan, P., Hercberg, S., et al., 2008 Feb. Artificial and natural ultraviolet radiation exposure: beliefs and behaviour of 7200 french adults. J. Eur. Acad. Dermatol. Venereol. 22 (2), 186e194. Fargnoli, M.C., Gandini, S., Peris, K., Maisonneuve, P., Raimondi, S., 2010 May. MC1R variants increase melanoma risk in families with CDKN2A mutations: a metaanalysis. Eur. J. Cancer 46 (8), 1413e1420. Gandini, S., Sera, F., Cattaruzza, M.S., Pasquini, P., Picconi, O., Boyle, P., et al., 2005a. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur. J. Cancer 41 (1), 45e60. Gandini, S., Sera, F., Cattaruzza, M.S., Pasquini, P., Abeni, D., Boyle, P., et al., 2005b. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur. J. Cancer 41 (1), 28e44. Gandini, S., Sera, F., Cattaruzza, M.S., Pasquini, P., Zanetti, R., Masini, C., et al., 2005c. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur. J. Cancer 41 (14), 2040e2059. Gandini, S., Raimondi, S., Gnagnarella, P., Dore, J.F., Maisonneuve, P., Testori, A., 2009 03. Vitamin D and skin cancer: a meta-analysis. Eur. J. Cancer 45 (4), 634e641. Gandini, S., Boniol, M., Haukka, J., Byrnes, G., Cox, B., Sneyd, M.J., et al., 2011 Mar 15. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int. J. Cancer 128 (6), 1414e1424. Garbe, C., Leiter, U., 2009 JaneFeb. Melanoma epidemiology and trends. Clin. Dermatol. 27 (1), 3e9. Green, A., 1992 Nov. A theory of site distribution of melanomas: Queensland, Australia. Cancer Causes Control 3 (6), 513e516. Han, J., Colditz, G.A., Hunter, D.J., 2006 Dec. Risk factors for skin cancers: a nested case-control study within the nurses’ health study. Int. J. Epidemiol. 35 (6), 1514e1521. Hery, C., Tryggvadottir, L., Sigurdsson, T., Olafsdottir, E., Sigurgeirsson, B., Jonasson, J.G., et al., 2010 Oct 1. A melanoma epidemic in Iceland: possible influence of sunbed use. Am. J. Epidemiol. 172 (7), 762e767.
Hirst, N., Gordon, L., Gies, P., Green, A.C., 2009 Mar. Estimation of avoidable skin cancers and cost-savings to government associated with regulation of the solarium industry in Australia. Health Policy 89 (3), 303e311. Holman, C.D., Armstrong, B.K., 1984a. Cutaneous malignant melanoma and indicators of total accumulated exposure to the sun: an analysis separating histogenetic types. J. Natl. Cancer Inst. 73 (1), 75e82. JID - 7503089. Holman, C.D., Armstrong, B.K., 1984b. Pigmentary traits, ethnic origin, benign nevi, and family history as risk factors for cutaneous malignant melanoma. J. Natl. Cancer Inst. 72 (2), 257e266. Holman, C.D., Armstrong, B.K., Heenan, P.J., 1986 03. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. J. Natl. Cancer Inst. 76 (3), 403e414. Hornung, R.L., Magee, K.H., Lee, W.J., Hansen, L.A., Hsieh, Y.C., 2003 Oct. Tanning facility use: are we exceeding food and drug administration limits? J. Am. Acad. Dermatol. 49 (4), 655e661. International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer, 2007 Mar 1. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int. J. Cancer 120 (5), 1116e1122. Lazovich, D., Forster, J., 2005 Jan. Indoor tanning by adolescents: prevalence, practices and policies. Eur. J. Cancer 41 (1), 20e27. Lazovich, D., Forster, J., Sorensen, G., Emmons, K., Stryker, J., Demierre, M.F., et al., 2004 Sep. Characteristics associated with use or intention to use indoor tanning among adolescents. Arch. Pediatr. Adolesc. Med. 158 (9), 918e924. Lazovich, D., Sweeney, C., Forster, J., 2005 Apr. Prevalence of indoor tanning use in Minnesota, 2002. Arch. Dermatol. 141 (4), 523e524. McGinley, J., Martin, C.J., MacKie, R.M., 1998 Sep. Sunbeds in current use in Scotland: a survey of their output and patterns of use. Br. J. Dermatol. 139 (3), 428e438. Osborne, J.E., Hutchinson, P.E., 2002 Aug. Vitamin D and systemic cancer: is this relevant to malignant melanoma? Br. J. Dermatol. 147 (2), 197e213. Osterlind, A., Tucker, M.A., Stone, B.J., Jensen, O.M., 1988 09/15. The Danish casecontrol study of cutaneous malignant melanoma. II. Importance of UV-light exposure. Int. J. Cancer 42 (3), 319e324. Raimondi, S., Johansson, H., Maisonneuve, P., Gandini, S., 2009 07. Review and metaanalysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 30 (7), 1170e1180. Rhainds, M., De Guire, L., Claveau, J., 1999 Apr. A population-based survey on the use of artificial tanning devices in the province of Quebec, Canada. J. Am. Acad. Dermatol. 40 (4), 572e576. Robinson, J.K., Kim, J., Rosenbaum, S., Ortiz, S., 2008 Apr. Indoor tanning knowledge, attitudes, and behavior among young adults from 1988e2007. Arch. Dermatol. 144 (4), 484e488. Ting, W., Schultz, K., Cac, N.N., Peterson, M., Walling, H.W., 2007 Dec. Tanning bed exposure increases the risk of malignant melanoma. Int. J. Dermatol. 46 (12), 1253e1257. Veierod, M.B., Adami, H.O., Lund, E., Armstrong, B.K., Weiderpass, E., 2010 Jan. Sun and solarium exposure and melanoma risk: effects of age, pigmentary characteristics, and nevi. Cancer Epidemiol. Biomarkers Prev. 19 (1), 111e120. Weinstock, M.A., Colditz, G.A., Willett, W.C., Stampfer, M.J., Bronstein, B.R., Mihm Jr., M.C., et al., 1989 Aug. Nonfamilial cutaneous melanoma incidence in women associated with sun exposure before 20 years of age. Pediatrics 84 (2), 199e204. Westerdahl, J., Olsson, H., Ingvar, C., 1994. At what age do sunburn episodes play a crucial role for the development of malignant melanoma [published erratum appears in Eur. J. cancer 1995; 31A (2): 287]. Eur. J. Cancer 30A (11), 1647e1654. Westerdahl, J., Ingvar, C., Masback, A., Jonsson, N., Olsson, H., 2000 05. Risk of cutaneous malignant melanoma in relation to use of sunbeds: further evidence for UV-A carcinogenicity. Br. J. Cancer 82 (0007e0920; 9), 1593e1599. Whiteman, D.C., 2010 May. Testing the divergent pathway hypothesis for melanoma: recent findings and future challenges. Expert Rev. Anticancer Ther. 10 (5), 615e618. Whiteman, D.C., Watt, P., Purdie, D.M., Hughes, M.C., Hayward, N.K., Green, A.C., 2003 06/04. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J. Natl. Cancer Inst. 95 (11), 806e812. JID - 7503089.
Contents lists available at SciVerse ScienceDirect
Progress in Biophysics and Molecular Biology journal homepage: www.elsevier.com/locate/pbiomolbio
Review
Reviews on sun exposure and artificial light and melanoma Sara Gandinia, *, Philippe Autierb, Mathieu Boniolb a b
European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy International Prevention Research Institute, 95 Cours Lafayette, 69006 Lyon, France
a r t i c l e i n f o
a b s t r a c t
Article history: Available online 19 September 2011
Melanoma is the most common form of cancer among young adults aged 25e29 years and the second most common cancer in those aged 15e29 years. We reviewed all the evidence regarding risk factors for melanoma, looking in particular at childhood exposure to ultraviolet radiation (UV). UV radiation is clearly the predominant environmental and thus potentially modifiable risk factor for melanoma. All activities related to tan-seeking behaviour and history of sunburns were shown to be significantly associated to melanoma. Host factors, such as pigmentary characteristics, and genetic predisposition plays also an important role. UV exposure is not only due to the sun but also to indoor tanning devices that have been shown to lead to an elevated risk of melanoma. The strongest evidence for a link between artificial UV and melanoma is found among individuals who had their first exposure to indoor tanning before the age of 30: they have a 75% increase risk of developing melanoma than individuals who had no exposure to indoor tanning. Prevention is very important, especially for children and young adults, as childhood and adolescence are critical periods in the development of later melanoma. Indoor tanning is a widespread practice in most developed countries, particularly in Northern Europe and the USA. In the recent decades more and more people, especially teenagers and women, are exposed to substantially high radiant exposures of UV through artificial sources and these trends raised a considerable concern. In fact the International Agency for Research on Cancer concluded that the association between skin cancer and exposure to solar radiation and the use of UV-emitting tanning devices are causal. Interesting analyses carried out in Iceland showed that when interventions to discourage sunbed use were introduced the incidence of melanoma among women decreased. All this evidence encouraged many countries to introduce regulations on sunbed use to avoid exposure before the age of 18. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: Ultraviolet radiation Indoor tanning Sun Melanoma
Contents 1. 2. 3. 4. 5. 6.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 Melanoma risk factors: phenotypic and genetic factors, sun exposure and childhood susceptibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Sun exposure, vitamin D and cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 Indoor tanning and skin cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 Prevalence of exposure to artificial UV for tanning purposes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
1. Introduction
* Corresponding author. E-mail address: [email protected] (S. Gandini). 0079-6107/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.pbiomolbio.2011.09.011
Over the last 25 years, cutaneous melanoma (CM) has become an increasingly common cause of cancer morbidity and mortality in
S. Gandini et al. / Progress in Biophysics and Molecular Biology 107 (2011) 362e366
Caucasian populations worldwide (Berwick et al., 2005; de Vries et al., 2003). The incidence rates of melanoma have also increased significantly in the last decade (Garbe and Leiter, 2009). The incidence of melanoma and non-melanoma skin cancer (NMSC) is increasing at a rapid rate, particularly among young women. Melanoma is the most common form of cancer among young adults aged 25e29 years and the second most common cancer in those aged 15e29 years (Christenson et al., 2005; Birch-Johansen et al., 2010). In this paper we reviewed all the evidence regarding all known risk factors for melanoma, looking in particular at childhood exposure to ultraviolet radiation (UV). Although much remains to be learned about the type, periodicity, and timing of sun exposure, UV radiation is clearly the predominant environmental and thus potentially modifiable risk factor for melanoma. Prevention is supremely important, especially for children and young adults, as childhood and adolescence are critical periods in the development of later melanoma. However UV exposure is not only due to the Sun but also to indoor tanning devices that have been shown to lead to an elevated risk of melanoma, especially in young adults (International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer, 2007). The modifying effect of host and genotypic factors has also been studied in many populations. Even if it is important to remember that sunlight is the most common source of vitamin D which has potential anti-carcinogenic properties, all types of UV radiation were classified by the International Agency for Research on Cancer (IARC) “carcinogenic to humans” (Group 1). The IARC concluded that the association between skin cancer and exposure to solar radiation and the use of UV-emitting tanning devices are causal (El Ghissassi et al., 2009). 2. Melanoma risk factors: phenotypic and genetic factors, sun exposure and childhood susceptibility Although solar UV exposure is the major established environmental risk factor for cutaneous malignant melanoma, the association is complex. In a meta-analysis summarising 57 studies on sun exposure and melanoma, we showed that intermittent sun exposures, such as all activities related to tan-seeking behaviour, and history of sunburns, a marker of intermittent exposure, substantially double the melanoma risk: Summary Relative Risk (SRR) ¼ 1.61 with 95% Confidential Interval (CI): (1.31, 1.99), and SRR: 2.03, with 95% CI: (1.73, 2.37) for intermittent sun exposure and sunburns respectively (Gandini et al., 2005a). Host factors are also important, with number of naevi which is associated to sun exposure, being the most powerful predictor of melanoma risk (Gandini et al., 2005b). In a meta-analysis on 47 studies we observed that number of common naevi, that is associated to sun exposure, is a key factor with a substantially increased risk associated 7 fold greater with the presence of 101e120 naevi compared with <15 naevi: SRR ¼ 6.89 (95% CI: 4.63, 10.25). Similar estimates were obtained for atypical naevi: SRR ¼ 6.36 (95% CI: 3.80, 10.33; for 5 versus 0 atypical naevi). Pigmentary characteristics such as hair, eye and skin colour and Fitzpatrick classification of skin’s sensitivity to sunburns and ability to tan, together with family history and actinic damage indicators, also determine melanoma susceptibility (Gandini et al., 2005c). Genetic predisposition plays also an important role. Hair colour is a phenotypic indicator of the Melanocortin-1-receptor (MC1R) genotype that may modify the association between naevi and melanoma risk. MC1R is one of the major genes that determine skin pigmentation. We performed a meta-analysis on the association between the MC1R variants and melanoma and/or red hair, fair skin phenotype. This meta-analysis provided evidence that some MC1R
363
variants are associated both with melanoma and phenotype, while other are only associated with melanoma development. These results suggest that MC1R variants could play a role in melanoma development both via pigmentary and non-pigmentary pathways (Fargnoli et al., 2010). A meta-analysis was performed to evaluate if CM risk factors differ depending on CM body site (Caini et al., 2009). High naevus counts are strongly associated with CM on usually not sun exposed body sites (P < 0.001) confirming that individuals with a high propensity for melanocyte proliferation tend to develop melanomas on intermittently sun exposed body sites. These results were in agreement with the hypothesis of different pathways for melanoma: one related to melanocytes instability and intermittent sun exposure and the other that required long sun exposure (Green, 1992; Whiteman et al., 2003; Whiteman, 2010). Migrant studies provide convincing evidence of childhood and adolescence being critical periods for the development of a later melanoma. They suggest that adults are at increased melanoma risk if they spent childhood in sunny geographical locations or generally received intermittent sun exposure during vacation and/or recreation. In an Australian case-control study published in 1984 (Holman and Armstrong, 1984a,b; Holman et al., 1986; English and Armstrong, 1988) age at arrival and duration of residence in Australia was studied. Earlier age at arrival was a predictor of melanoma risk with little residual effect of duration of residence. Specifically, migrants arriving before age 10 years appeared to have a risk similar to that of native born Australians, whereas the estimated incidence in those arriving after age 15 years was around one quarter of the native born rate, with arrival at later ages giving no additional advantage. Similarly, in an European case-control study, age <10 years old at arrival in a sunny location of residence (that is, the Mediterranean, subtropics, or tropics) conferred a fourfold increased risk of developing melanoma (Autier et al., 1997). In addition to migrant studies, location of residence studies provide further evidence that sun exposure in childhood and adolescence is closely associated with melanoma risk. A nested case-control analysis from the Nurses’ Health Study cohort (Weinstock et al., 1989) showed an increased risk of melanoma in women whose residence during the ages 15e20 years was more equatorial in latitude whereas latitude of residence after 30 years of age was not significantly related to melanoma risk. In another study of 474 cases and 926 controls, those who lived near the coast before the age of 15 years had an increased risk of melanoma compared to those who never lived near the coast (OR ¼ 1.6; 95% CI 1.0e2.6) (Osterlind et al., 1988). 3. Sun exposure, vitamin D and cancer Worldwide photosynthesis from sunlight is the most common source of vitamin D. 25-hydroxyvitamin D (25OHD), which is the main circulating and storage form of Vitamin D, undergoes 1ahydroxylation in the kidney to form the active hormone, 1,25dihyroxyvitamin D. 1,25-dihyroxyvitamin D was shown to be an anti-proliferative, pro-differentiation and pro-apoptotic agent (Osborne and Hutchinson, 2002; Deeb et al., 2007). We performed a meta-analysis of observational studies of serum 25-hydroxyvitamin D level and colorectal, breast and prostate cancer. Because in caseecontrol studies, serum 25-hydroxyvitamin D level is measured after the diagnosis of cancer, separate analyses for caseecontrol and prospective studies were done. The analysis of 35 independent studies showed that 10 ng/ml increase in serum 25-hydroxyvitamin D was associated to a significant decreased risk for colorectal cancer: SRR ¼ 0.85 (95% CI: 0.79, 0.91). For breast
364
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cancer caseecontrol studies had major limitations and we concluded that the association with breast and prostate cancer were not convincing (Gandini et al., 2011). The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. We performed a meta-analysis on the association between the two most studied VDR polymorphisms (FokI and BsmI) and any cancer site. Results showed that the two polymorphisms might modulate the risk of cancer of skin, breast, and prostate and possibly affect cancer risk at any site in Caucasians (Gandini et al., 2009; Raimondi et al., 2009). 4. Indoor tanning and skin cancer For most individuals, the main source of exposure to ultraviolet radiation is the sun. Nevertheless, some individuals are exposed to substantially high doses of UV through artificial sources. Sunbeds and sunlamps used for tanning purposes are the major source of deliberate exposure to UV radiations. In 2007 we published a meta-analysis summarising twentythree observational studies (22 caseecontrol, one cohort) that investigated the association between indoor tanning use and risk for melanoma, and 7 caseecontrol studies for keratinocytic skin cancers. Among the 19 informative studies, the summary relative risk estimate forever versus never use of indoor tanning was 1.14 (95% CI: 1.00, 1.31). When the analysis was restricted to the nine population-based caseecontrol studies and the cohort study, the SRR was 1.18 (95% CI: 0.97, 1.43). All studies that examined age at first exposure found an increased risk for melanoma when exposure started before approximately 30 years of age, with a summary relative risk estimate of 1.75 (95% CI: 1.35, 2.26). Studies on exposure to indoor tanning and squamous cell carcinoma found some evidence for an increased risk for squamous cell carcinoma. Studies on basal cell carcinoma did not support an association with use of indoor tanning facilities (International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer, 2007). Given the estimates of the meta-analysis Hirst et al. (2009) estimated the numbers of potential skin cancers prevented through regulation of solaria and the associated cost-savings to the Federal Government. The results was that with stricter regulations, between 18 and 31 melanomas, 200e251 squamous cell carcinomas and associated costs of $AU 256,054 would be avoided per 100,000 persons. In the previous meta-analysis we were not able to carry out a doseeresponse meta-analysis because there were not enough published data. Recently some studies published data on trend by time, age and number of sessions. After our meta-analysis, a further big study was published: a caseecontrol study nested within the Nurses’ Health Study. Results showed that sunlamp usage or tanning salon attendance was significantly associated to melanoma after adjusting for potential confounding variables (OR for ‘ever’ versus ‘never’ usage, 2.06, 95% CI: 1.30, 3.26) (Han et al., 2006). In a survey conducted in dermatological clinics in US, women aged 45 years or younger accounted for about 60% of all tanning bed users. In the entire cohort, the “ever-use” of tanning beds was found to be a significant risk factor for the development of melanoma [OR, 1.64; 95% CI: 1.01, 2.67]. The risk was greater in women aged 45 years or younger (OR, 3.22; 95% CI: 1.01, 11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min (OR, 3.18; 95% CI: 1.48, 6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI: 1.41, 12.02) (Ting et al., 2007). Results from the Australian Melanoma Family Study, a multicentre population-based caseecontrol study, confirmed sunbed use
as a risk factor for increasing with greater use, an earlier age at first use and for earlier onset disease: RR ¼ 1.41 (95% CI: 1.01, 1.96) for ever use, and 2.01 (95% CI: 1.22, 3.31) for more than 10 lifetime sessions (P trend 0.01 with cumulative use). The association was stronger for earlier age at first use (P trend 0.02). The association was also stronger for melanoma diagnosed at 18e29 years of age than for melanoma diagnosed at 30e39 years of age: for more than 10 lifetime sessions OR was 6.57 (95% CI: 1.41, 30.49) and 1.60 (95% CI: 0.92, 2.77) for the younger and the older age group respectively (P ¼ 0.01). Among those who had ever used a sunbed and were diagnosed between 18 and 29 years of age, three quarters (76%) of melanomas were attributable to sunbed use (Cust et al., 2011). In a population-based caseecontrol study in UK, those starting sunlamp use at <20 years had an OR ¼ 1.23 (95% CI: 0.81, 1.88) and those starting at >20 years an OR ¼ 1.71 (95% CI: 1.00e2.92). Data suggested increasing risk with number of sunlamp uses and with duration of use (P ¼ 0.02). The OR was 1.96 (95% CI: 1.06e3.61) for having used sunbed and sunlamp (Clough-Gorr et al., 2008). Results from the big prospective cohort study published by Veierod et al. in 2003 were updated with a longer follow-up confirming an increase risk for exposure to indoor tanning. The cohort included 106,366 followed-up from 1991 through 2005 and the RRs increased from 1.24 for rarely use one, two, or three decades from 10 to 39 years to 1.38 for use one or more times per month in one of the three decades to 2.37 for use one or more times per month in two or three decades (P trend ¼ 0.003). The authors found little indication that the relative effects of solarium use varied with hair colour, cutaneous sun sensitivity, or presence of asymmetric large naevi (Veierod et al., 2010). This is further important strong piece of evidence since the statistical power is high and the chance of uncontrolled bias in this big prospective cohort study is very low. Hery et al. (2010) presented a fascinating analysis of an ecologic association of melanoma trends in Iceland. In this study, the authors note a sharp increase in melanoma incidence among young women that began after 1990 with a peak in 2000. At the same time the prevalence of sunbeds in Iceland rapidly increased from 1979 to 1988. They also observed a decline in melanoma rates among women after 2001, following a reduction in prevalence of sunbed use. Despite its reliance on population-level data, this study provides further evidence of causality for sunbed showing that implementation of public health interventions to decrease sunbed use resulted in a concomitant decrease in melanoma rates. 5. Prevalence of exposure to artificial UV for tanning purposes Indoor tanning is a widespread practice in most developed countries, particularly in Northern Europe and the USA. Even in Australia there is growing concern about the expanding solarium industry, particularly among women and young people. Already in 1996 in Canada a survey indicated that a 20% of the adult respondents reported to have used, at least once, a tanning device in a commercial tanning salon during the last 5 years before the survey (Rhainds et al., 1999). In the last decades the prevalence increased: in 2002 in USA a report describing prevalence of indoor tanning use in adults showed an increase prevalence: 38% of adults had ever used indoor tanning facilities (Lazovich et al., 2004). Generally in northern Europe the prevalence is even greater. A caseecontrol study conducted in 1991 in 5 centres in Belgium, France and Germany showed that the proportion of controls that had ever exposed themselves to a sunlamp or a sunbed was higher in Germany (25%) than in Belgium (20%) and in France (6%) (Autier et al., 1994). In a caseecontrol study conducted by the same investigators between 1998 and 2000 in Belgium, France, Sweden (Bataille et al., 2005), the Netherlands and the United Kingdom
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(Autier and Dore, 1998) among persons younger than 50 years (mean age of controls, 37 years), 57% of controls had ever exposed themselves to artificial UV tanning, the highest prevalence of use being found in Sweden (87%) (Bataille et al., 2005). Prevalence in teenagers is worrisome. Two cross-sectional population-based surveys of US youths ages 11e18 years, conducted in 1998 and 2004, showed that the prevalence of indoor tanning use within the past year was around 10%. Half of adolescent indoor tanners in the US used indoor tanning >6 times during the past year and fifty-eight percent of users reported burns from indoor tanning (Cokkinides et al., 2009). In Sweden, according to two studies conducted within the same population in 1988e1990 and in 1995e1997, the prevalence of exposure doubled in 7 years. In 1988e1990, 46% of individuals younger than 30 years had ever exposed themselves to sunlamps or solaria (56% of women and 12% of men, these figures being higher in the 15e24 years age group) while this proportion was only of 24% among individuals older than 30 years (31% of women and 16% of men) (Westerdahl et al., 1994). After 1995, the prevalence of solarium use in the population aged 16e80 years was 41%, but 70% of women and 50% of men aged 18e50 years reported the use of a solarium (Westerdahl et al., 2000). In a survey carried out in USA and published in 2008 the authors found that knowledge of limiting tanning to help prevent melanoma increased from 1988 (25%) to 1994 (77%), but decreased from 1994 to 2007 (67%). This decline in knowledge about limiting tanning was concurrent with an increase in the attitude that having a tan looks better (1994, 69%; 2007, 81%) (Robinson et al., 2008). A survey from USA comparing prevalence by gender indicated that few men and women had used a tanning device before 1980. Women were almost twice as likely as men to report tanning indoors during the 1980s (19% versus 10%), but in the following decades, the proportion of men using indoor tanning facilities approached that of women (15% versus 17% in the 1990s) (Lazovich et al., 2004). Use of indoor tanning facilities is generally more prevalent among women. In 2001, a survey on 12,741 adult volunteers in France (SU.VI.MAX cohort) reported almost three times women having ever experienced indoor tanning than men (22% women and 8% men) (Ezzedine et al., 2008). Cokkinides et al. (2009) showed an increase in the prevalence of past year use of indoor tanning among girls (from 15.6% to 17.7%) and youths ages 14e15 years (from 7.1% to 10.5%). In general younger age (<35 years) is significantly associated with higher likelihood of using indoor tanning facilities among both men and women. In a caseecontrol study comparing data in different European countries (Bataille et al., 2005), exposure before the age of 15 years was reported in 3% of all controls, but reached 20% in Sweden. The mean age at first exposure was 20 years in Sweden, 23 years in the United Kingdom and 27 years in France. Since 1989, a total of 16 studies (18 reports) examined indoor tanning among children and adolescents aged 8e19 years (Lazovich and Forster, 2005; Lazovich et al., 2004). Studies were conducted in Europe (Norway, Sweden and United Kingdom), in various locations throughout the USA (including two nationally representative samples) and in Australia. All these studies showed a frequent use by adolescents and children, sometimes at a very young age. Thirty percent of adolescents in Sweden and 24% of adolescents in the USA aged 13e19 years reported ever use of indoor tanning facilities, and 8% and 12% respectively are frequent users (10 times per year or more). Considering frequency of use, a survey demonstrated that in Scotland 31% of 205 responders had more than five sunbed sessions
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in a year and, for 16% of them, this amounted to over 100 sessions per year (McGinley et al., 1998). In a US survey (Lazovich et al., 2005; Lazovich and Forster, 2005) the median number of times of use was 10 for men and 20 for women, and 21% of women reported frequent use (defined as more than 30 times). A community-based survey was administered in USA to verify if tanning bed operators and patrons are compliant with the US Food and Drug Administration (FDA) exposure limits. In the study published in 2003, out of 483 users 95% were exceeding the recommended exposure times. The average period of tanning for each user was 6.3 weeks (Hornung et al., 2003). 6. Conclusions All activities related to tan-seeking behaviour and history of sunburns were shown to be significantly associated to melanoma. Host factors, such as pigmentary characteristics, and genetic predisposition plays also an important role. Probably individuals with various phenotypes need different pattern of UV exposure to get melanoma. However we have to remember that photosynthesis from sunlight is the most common source of vitamin D that seems to be associated to a reduce risk of several other cancer sites. In the recent decades more and more people, especially teenagers and women, are exposed to substantially high radiant exposures of UV through artificial sources and these trends raised a considerable concern. In fact the International Agency for Research on Cancer (IARC) classified tanning beds and other UVemitting tanning devices as Group 1 carcinogens, meaning that there is sufficient evidence to conclude that these devices cause cancer in humans. The strongest evidence for a link between artificial UV and melanoma is found among individuals who had their first exposure to indoor tanning before the age of 30: they have a 75% increase risk of developing melanoma than individuals who had no exposure to indoor tanning. Hery et al. presented data to suggest that when in Iceland interventions to discourage sunbed use were introduced, the incidence of melanoma among women decreased Hery et al., 2010. All this evidence encouraged many countries to introduce regulations on sunbed use to avoid exposure before the age of 18. Finally in Brazil a government working group was established to review existing legislation, and after extensive discussions with health authorities and the sunbed industry, it was determined that the health benefits of sunbed tanning were little or none, certainly not enough to outweigh their dangers. The Brazilian National Health Surveillance Agency banned UV cosmetic tanning altogether throughout the country (Cumberland and Jurberg, 2009). References Autier, P., Dore, J.F., 1998 08/12. Influence of sun exposures during childhood and during adulthood on melanoma risk. EPIMEL and EORTC melanoma cooperative group. European organisation for research and treatment of cancer. Int. J. Cancer 77 (4), 533e537. Autier, P., Dore, J.F., Lejeune, F., Koelmel, K.F., Geffeler, O., Hille, P., et al., 1994 09/15. Cutaneous malignant melanoma and exposure to sunlamps or sunbeds: an EORTC multicenter case-control study in Belgium, France and Germany. EORTC melanoma cooperative group. Int. J. Cancer 58 (6), 809e813. Autier, P., Dore, J.F., Gefeller, O., Cesarini, J.P., Lejeune, F., Koelmel, K.F., et al., 1997. Melanoma risk and residence in sunny areas. EORTC melanoma co-operative group. European organization for research and treatment of cancer. Br. J. Cancer 76 (11), 1521e1524. Bataille, V., Boniol, M., De Vries, E., Severi, G., Brandberg, Y., Sasieni, P., et al., 2005 Sep. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe. Eur. J. Cancer 41 (14), 2141e2149. Berwick, M., Armstrong, B.K., Ben-Porat, L., Fine, J., Kricker, A., Eberle, C., et al., 2005 02/02. Sun exposure and mortality from melanoma. J. Natl. Cancer Inst. 97 (3), 195e199. Birch-Johansen, F., Jensen, A., Mortensen, L., Olesen, A.B., Kjaer, S.K., 2010 Nov 1. Trends in the incidence of nonmelanoma skin cancer in Denmark 1978e2007: rapid incidence increase among young Danish women. Int. J. Cancer 127 (9), 2190e2198.
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Caini, S., Gandini, S., Sera, F., Raimondi, S., Fargnoli, M.C., Boniol, M., et al., 2009 06/ 20. Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant. Eur. J. Cancer. Christenson, L.J., Borrowman, T.A., Vachon, C.M., Tollefson, M.M., Otley, C.C., Weaver, A.L., et al., 2005 Aug 10. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA 294 (6), 681e690. Clough-Gorr, K.M., Titus-Ernstoff, L., Perry, A.E., Spencer, S.K., Ernstoff, M.S., 2008 Sep. Exposure to sunlamps, tanning beds, and melanoma risk. Cancer Causes Control 19 (7), 659e669. Cokkinides, V., Weinstock, M., Lazovich, D., Ward, E., Thun, M., 2009 Jan 1. Indoor tanning use among adolescents in the US, 1998 to 2004. Cancer 115 (1), 190e198. Cumberland, S., Jurberg, C., 2009 August. From Australia to Brazil: sun worshippers beware. Bull. World Health Organ. 87 (8), 574e575. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC2733274. Cust, A.E., Armstrong, B.K., Goumas, C., Jenkins, M.A., Schmid, H., Hopper, J.L., et al., 2011 May 15. Sunbed use during adolescence and early adulthood is associated with increased risk of early-onset melanoma. Int. J. Cancer 128 (10), 2425e2435. Deeb, K.K., Trump, D.L., Johnson, C.S., 2007 09. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat. Rev. Cancer 7 (9), 684e700. de Vries, E., Bray, F.I., Coebergh, J.W., Parkin, D.M., 2003 10/20. Changing epidemiology of malignant cutaneous melanoma in Europe 1953e1997: rising trends in incidence and mortality but recent stabilizations in western Europe and decreases in Scandinavia. Int. J. Cancer 107 (1), 119e126. El Ghissassi, F., Baan, R., Straif, K., Grosse, Y., Secretan, B., Bouvard, V., et al., 2009 Aug. A review of human carcinogens e part D: radiation. Lancet Oncol. 10 (8), 751e752. English, D.R., Armstrong, B.K., 1988 05/07. Identifying people at high risk of cutaneous malignant melanoma: results from a case-control study in western Australia. Br. Med. J. (Clin. Res. Ed.) 296 (6632), 1285e1288. Ezzedine, K., Malvy, D., Mauger, E., Nageotte, O., Galan, P., Hercberg, S., et al., 2008 Feb. Artificial and natural ultraviolet radiation exposure: beliefs and behaviour of 7200 french adults. J. Eur. Acad. Dermatol. Venereol. 22 (2), 186e194. Fargnoli, M.C., Gandini, S., Peris, K., Maisonneuve, P., Raimondi, S., 2010 May. MC1R variants increase melanoma risk in families with CDKN2A mutations: a metaanalysis. Eur. J. Cancer 46 (8), 1413e1420. Gandini, S., Sera, F., Cattaruzza, M.S., Pasquini, P., Picconi, O., Boyle, P., et al., 2005a. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur. J. Cancer 41 (1), 45e60. Gandini, S., Sera, F., Cattaruzza, M.S., Pasquini, P., Abeni, D., Boyle, P., et al., 2005b. Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi. Eur. J. Cancer 41 (1), 28e44. Gandini, S., Sera, F., Cattaruzza, M.S., Pasquini, P., Zanetti, R., Masini, C., et al., 2005c. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur. J. Cancer 41 (14), 2040e2059. Gandini, S., Raimondi, S., Gnagnarella, P., Dore, J.F., Maisonneuve, P., Testori, A., 2009 03. Vitamin D and skin cancer: a meta-analysis. Eur. J. Cancer 45 (4), 634e641. Gandini, S., Boniol, M., Haukka, J., Byrnes, G., Cox, B., Sneyd, M.J., et al., 2011 Mar 15. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int. J. Cancer 128 (6), 1414e1424. Garbe, C., Leiter, U., 2009 JaneFeb. Melanoma epidemiology and trends. Clin. Dermatol. 27 (1), 3e9. Green, A., 1992 Nov. A theory of site distribution of melanomas: Queensland, Australia. Cancer Causes Control 3 (6), 513e516. Han, J., Colditz, G.A., Hunter, D.J., 2006 Dec. Risk factors for skin cancers: a nested case-control study within the nurses’ health study. Int. J. Epidemiol. 35 (6), 1514e1521. Hery, C., Tryggvadottir, L., Sigurdsson, T., Olafsdottir, E., Sigurgeirsson, B., Jonasson, J.G., et al., 2010 Oct 1. A melanoma epidemic in Iceland: possible influence of sunbed use. Am. J. Epidemiol. 172 (7), 762e767.
Hirst, N., Gordon, L., Gies, P., Green, A.C., 2009 Mar. Estimation of avoidable skin cancers and cost-savings to government associated with regulation of the solarium industry in Australia. Health Policy 89 (3), 303e311. Holman, C.D., Armstrong, B.K., 1984a. Cutaneous malignant melanoma and indicators of total accumulated exposure to the sun: an analysis separating histogenetic types. J. Natl. Cancer Inst. 73 (1), 75e82. JID - 7503089. Holman, C.D., Armstrong, B.K., 1984b. Pigmentary traits, ethnic origin, benign nevi, and family history as risk factors for cutaneous malignant melanoma. J. Natl. Cancer Inst. 72 (2), 257e266. Holman, C.D., Armstrong, B.K., Heenan, P.J., 1986 03. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. J. Natl. Cancer Inst. 76 (3), 403e414. Hornung, R.L., Magee, K.H., Lee, W.J., Hansen, L.A., Hsieh, Y.C., 2003 Oct. Tanning facility use: are we exceeding food and drug administration limits? J. Am. Acad. Dermatol. 49 (4), 655e661. International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer, 2007 Mar 1. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int. J. Cancer 120 (5), 1116e1122. Lazovich, D., Forster, J., 2005 Jan. Indoor tanning by adolescents: prevalence, practices and policies. Eur. J. Cancer 41 (1), 20e27. Lazovich, D., Forster, J., Sorensen, G., Emmons, K., Stryker, J., Demierre, M.F., et al., 2004 Sep. Characteristics associated with use or intention to use indoor tanning among adolescents. Arch. Pediatr. Adolesc. Med. 158 (9), 918e924. Lazovich, D., Sweeney, C., Forster, J., 2005 Apr. Prevalence of indoor tanning use in Minnesota, 2002. Arch. Dermatol. 141 (4), 523e524. McGinley, J., Martin, C.J., MacKie, R.M., 1998 Sep. Sunbeds in current use in Scotland: a survey of their output and patterns of use. Br. J. Dermatol. 139 (3), 428e438. Osborne, J.E., Hutchinson, P.E., 2002 Aug. Vitamin D and systemic cancer: is this relevant to malignant melanoma? Br. J. Dermatol. 147 (2), 197e213. Osterlind, A., Tucker, M.A., Stone, B.J., Jensen, O.M., 1988 09/15. The Danish casecontrol study of cutaneous malignant melanoma. II. Importance of UV-light exposure. Int. J. Cancer 42 (3), 319e324. Raimondi, S., Johansson, H., Maisonneuve, P., Gandini, S., 2009 07. Review and metaanalysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 30 (7), 1170e1180. Rhainds, M., De Guire, L., Claveau, J., 1999 Apr. A population-based survey on the use of artificial tanning devices in the province of Quebec, Canada. J. Am. Acad. Dermatol. 40 (4), 572e576. Robinson, J.K., Kim, J., Rosenbaum, S., Ortiz, S., 2008 Apr. Indoor tanning knowledge, attitudes, and behavior among young adults from 1988e2007. Arch. Dermatol. 144 (4), 484e488. Ting, W., Schultz, K., Cac, N.N., Peterson, M., Walling, H.W., 2007 Dec. Tanning bed exposure increases the risk of malignant melanoma. Int. J. Dermatol. 46 (12), 1253e1257. Veierod, M.B., Adami, H.O., Lund, E., Armstrong, B.K., Weiderpass, E., 2010 Jan. Sun and solarium exposure and melanoma risk: effects of age, pigmentary characteristics, and nevi. Cancer Epidemiol. Biomarkers Prev. 19 (1), 111e120. Weinstock, M.A., Colditz, G.A., Willett, W.C., Stampfer, M.J., Bronstein, B.R., Mihm Jr., M.C., et al., 1989 Aug. Nonfamilial cutaneous melanoma incidence in women associated with sun exposure before 20 years of age. Pediatrics 84 (2), 199e204. Westerdahl, J., Olsson, H., Ingvar, C., 1994. At what age do sunburn episodes play a crucial role for the development of malignant melanoma [published erratum appears in Eur. J. cancer 1995; 31A (2): 287]. Eur. J. Cancer 30A (11), 1647e1654. Westerdahl, J., Ingvar, C., Masback, A., Jonsson, N., Olsson, H., 2000 05. Risk of cutaneous malignant melanoma in relation to use of sunbeds: further evidence for UV-A carcinogenicity. Br. J. Cancer 82 (0007e0920; 9), 1593e1599. Whiteman, D.C., 2010 May. Testing the divergent pathway hypothesis for melanoma: recent findings and future challenges. Expert Rev. Anticancer Ther. 10 (5), 615e618. Whiteman, D.C., Watt, P., Purdie, D.M., Hughes, M.C., Hayward, N.K., Green, A.C., 2003 06/04. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J. Natl. Cancer Inst. 95 (11), 806e812. JID - 7503089.