Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e4757 (Published 24 July 2012)
Cite this as: BMJ 2012;345:e4757

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Increasing indoor UV tanning is leading to increased melanoma incidence (BMJ 2012;345:e4757). Surprisingly, recommendations against UV exposure are coming from an equally trendy source--tattoo artists. Tattoos constitute an ancient form of body modification, globally used for religious, cultural, and personal expression. Tattoos once found mainly on male motorcyclists, sailors and military personnel, now appear on one in four persons of both genders.(1-3) Tattoos remain more common among individuals with greater risk taking behavior—those who are younger, lower paid, less educated, use recreational drugs, drink alcohol, or have served time in prison.(2)

While many governments regulate tattoo parlors to ensure patient safety, post tattoo care instructions are not standardized.(4) On January 4, 2012, we explored post-tattoo care instructions by conducting a Google® search using the terms “tattoo care” and archived the top 50 web results using WebCite®. Four researchers (ES, MS, JTJ, MF) categorized the results by consensus (Table 1).

The most common recommendation (30/50) was to avoid manipulation at the tattoo site. The next most common recommendations were to apply non-antibiotic ointment (25/50), to keep the site dry (25/50), and to use sunscreen to prevent the tattoo ink from fading (25/50). Two other frequent recommendations were to avoid UV exposure long term (19/50) and to avoid sunburning the tattoo (13/50).

Although much of the focus was restricted to tattoo preservation and widespread UV protection is not emphasized, these results reveal online tattoo care instructions as a surprising source of UV protection advice, targeted to a population associated with risky health behaviors. As both tanning bed popularity and melanoma continue to rise, a unique opportunity to further educate tattoo artists on sun safety, and expand their UV recommendations to their cliental presents itself.

References

[1] Urdang M, Mallek J, Mallon, W. Tattoos and Piercing: A Review for the Emergency Department Physician. West J Emerg Med. 2011;12(4): 393-398.

[2] Heywood, W, K Patrick, et al. "Who Gets Tattoos? Demographic and Behavioral Correlates of Ever Being Tattooed in a Representative Sample of Men and Women ." Annals of Epidemiology. 22.1 (2012): 51-56. Web. 5 Jan. 2012

[3] Laumann A, Derick A. Tattoos and body piercings in the United States: a national data set. J Am Acad Dermatol. 2006; 55:413–421.

[4] SeverJ.TheHarrisPollNo.58, October8, 2003. Harris Interactive Website. Available at: http://harrisinteractive.com/harris_poll/printerfriend/ index.asp?PID1⁄4407. Accessed April 23, 2008.

Competing interests: None declared

Emilee K. Sandsmark, Medical student

Monica Salazar, Jamira Jones, Marie Freyta, Barbara Walkosz, Robert Dellavalle

University of Colorado School of Medicine, Building 500 - 13001 E. 17th Place, Campus Box C290, Room E1354, Aurora, CO 80045

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I thank the authors of Ref. 1 for responding to my rapid response and expanding the discussion of our different opinions [2]. In this response, I respond to specific points in their response, then discuss the more general questions regarding the evidence that UVB irradiance is more beneficial than harmful and that the evidence for beneficial effects of vitamin D without adverse effects is strong.

Regarding randomized controlled trials (RCTs), one was recently published reporting that a median intake of 800 IU/d vitamin D was associated with a 30% reduction in hip fracture rate [3]. Regarding a secondary analysis of the Women’s Health Initiative study based on the subset of participants who did not take personal calcium or vitamin D supplements prior to enrollment in the study [4], that approach has been proposed as a way of “correcting for errors in design or adjusting for problems in execution” of RCTs [5]. As noted in a recent paper, there are many problems inherent in designing and executing RCTs with vitamin D including knowing the serum 25-hydroxyvitamin D [25(OH)D] concentration-disease outcome relation, choosing participants who have 25(OH)D concentrations near the low end of the relation, giving sufficient vitamin D to increase 25(OH)D concentrations to the upper end of the relation, and measuring 25(OH)D concentrations after supplementation [6,7]. Unfortunately, the Women’s Health Initiative calcium and vitamin D supplementation study did not follow any of these criteria.

Regarding the recent finding in the Danish study of a J-shaped relation between serum 25(OH)D concentration and all-cause mortality rate observed during a mean three-year follow-up period [8], a possible explanation for the finding was that those with higher serum 25(OH)D concentrations (75-150 nmol/l) had started taking vitamin D supplements shortly before the blood draw because they were advised to do so by their physician, perhaps after diagnosis of osteoporosis. Vitamin D cannot overcome all of the adverse effects of low 25(OH)D concentrations for much of the lifetime. In support of this hypothesis are two recent studies of frailty index with respect to serum 25(OH)D concentrations in 4+ year follow-up studies: for men, higher 25(OH)D was associated with lower frailty index [9] but for women, there was a U-shaped relation [10].

The statement in [2]: “A key hypothesis to explain the discrepancy between observational and experimental studies would be the diversity of physiological functions of vitamin D in virtually all body organs. Low vitamin D status could be a reflection of metabolic disturbances found in patients with obesity, chronic inflammatory diseases, chronic heart failure, chronic kidney disease, particularly the bedridden, or those at the end of life.” is neither accurate [11] nor useful since many of the observational studies either not include such cases and the experimental studies to date have not been well conducted.

Regarding the Swedish Women’s Lifestyle and Health cohort study, regular use of a sunbed was associated with a reduced risk of breast cancer [12], not increased as claimed in [2]. It is noted that women in Nordic countries apparently have much less solar UVB irradiance than men since in a study of cancer related to occupation, outdoor occupations were associated with reduced risk of only three types of cancer for women but 14 types for men [13].

Regarding the carcinogenicity of UV radiation, as I stated in my original response [14], it is not the increased risk of melanoma per se that is important but, rather, whether the health benefits of artificial UV irradiance are outweigh the health risks. In my analysis, I found that it did by a wide margin. However, the estimate of benefit was overstated. An alternate calculation based on assuming that melanoma risks and cancer risk reduction associated with sunbed use are the same as those for above average solar UV irradiance. (Ref. 1 points out that sunbeds emit primarily UVA with <5% in the UVB range. This is the same as midday, midlatitude solar UV hitting the earth’s surface.) Using a value of a 15% reduction in overall cancer incidence rates for high vs. low serum 25(OH)D concentrations for Europe [4,6,13] using incidence data for the European Union [15] and assuming that all melanoma incidence is due to UV irradiance results in a ratio of 6.1 to 1 for males and 4.6 to one for females. Doing the same analysis for mortality rates yields a ratio of 13.3 for males and 12.7 for females. The discrepancy between incidence and mortality rates may be due to “excess” diagnosis of melanoma [16].

Of course vitamin D supplements could be used for the health benefits of UVB irradiance, but it is difficult to obtain high-dose vitamin D supplements in Europe. The same reasoning also applies to solar UVB irradiance. Solar UVB is the primary source of vitamin D for most people, e.g. [17], and human skin pigmentation has adapted to where people live for many generations to optimize vitamin D production while protecting against the adverse effects of UV [18]. In a review commissioned by the World Health Organization, it was stated that “UVR exposure is a minor contributor to the world's disease burden, causing an estimated annual loss of 1.6 million DALYs; i.e. 0.1% of the total global disease burden. A markedly larger annual disease burden, 3.3 billion DALYs, might result from reduction in global UVR exposure to very low levels.” [19] The accompanying commentary states: “But the importance of the exercise undertaken by Lucas et al. is to make clear that unless dietary/supplement intake in fact substitutes for some UV exposure, there are potentially substantial risks to markedly reducing UV exposure. What is clear is that the shaping of sun exposure policy should not ignore the major benefits of vitamin D, while at the same time acknowledging that UV is a known carcinogen and responsible for skin cancer and other ill effects.” [20]

Let’s turn now to evidence. Meta-analyses of observational studies are considered nearly as strong as RCTs. In fact, the analysis in [1] is just that. There are no RCTs of UV irradiance and risk of melanoma in humans as such studies would be both unethical and take many years. Since they are observational studies, they are subject to confounding, primarily from not considering skin type in the earlier studies and from solar UV irradiance, which is difficult to quantify. Meta-analyses have found significant inverse correlations between serum 25(OH)D concentrations and incidence of colorectal [21] and breast [22] cancer, diabetes and cardiovascular disease [23], and all-cause mortality rate [24,25]. The observational studies of breast and colorectal cancer are in excellent agreement with ecological studies [25]. Such ecological studies were recently supported in a large-scale prospective study that found solar UVB doses in the U.S. associated with a 22% (95% confidence interval 13%-32%) increased risk of melanoma but 9% to 43% reduced risk of bladder, colon, kidney, squamous cell lung, pleural, prostate and overall cancer and non-Hodgkin’s lymphoma [27].

References
1.Boniol M, Autier P, Boyle P, Gandini S. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ 2012;345:e4757.
2. Boniol M, Autier P, Boyle P, Gandini S. Re: Answer to the rapid response of WB Grant. BMJ 27 July 2012.
3. Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 2012;367:40-9.
4. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011;94:1144-9.
5. Kristal AR. Are clinical trials the "gold standard" for cancer prevention research? Cancer Epidemiol Biomarkers Prev 2008;17:3289-91.
6. Lappe JM, Heaney RP. Why randomized controlled trials of calcium and vitamin D sometimes fail. Dermatoendocrin 2012;4(2) epub
7. Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011;31:617-22.
8. Durup D, Jørgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice, the CopD Study. J Clin Endocrinol Metab 2012 May 9. [Epub ahead of print]
9. Ensrud KE, Blackwell TL, Cauley JA, Cummings SR, Barrett-Connor E, Dam TT, et al. Circulating 25-hydroxyvitamin D levels and frailty in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 2011;59:101-6.
10. Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA, et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab 2010;95:5266-73.
11. Fung GJ, Steffen LM, Zhou X, Harnack L, Tang W, Lutsey PL, et al. Vitamin D intake is inversely related to risk of developing metabolic syndrome in African American and white men and women over 20 y: the Coronary Artery Risk Development in Young Adults study. Am J Clin Nutr 2012;96:24-9.
12. Yang L, Veierød MB, Löf M, Sandin S, Adami HO, Weiderpass E. Prospective Study of UV Exposure and Cancer Incidence among Swedish Women. Cancer Epidemiol Biomarkers Prev 2011;20:1358-67.
13. Grant WB. Role of solar UV irradiance and smoking in cancer as inferred from cancer incidence rates by occupation in Nordic countries. Dermatoendocrinol 2012;4(2) epub
14. Grant WB. Re: Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ 25 July 2012.
15. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-917. http://globocan.iarc.fr/factsheet.asp
16. Weyers W. The 'epidemic' of melanoma between under- and overdiagnosis. J Cutan Pathol. 2012;39:9-16.
17. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr 2007;85:860-8.
18. Jablonski NG. The evolution of human skin colouration and its relevance to health in the modern world. J R Coll Physicians Edinb 2012;42:58-63.
19. Lucas RM, McMichael AJ, Armstrong BK, Smith WT. Estimating the global disease burden due to ultraviolet radiation exposure. Int J Epidemiol 2008;37:654-67.
20. Freedman DM. Commentary: The complexities of minimizing risks due to UV exposures. Int J Epidemiol 2008;37:667-8.
21. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther 2009;30:113-25.
22. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: Serum vitamin D and breast cancer risk. Eur J Cancer 2010;46:2196-205.
23. Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, et al. Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas 2010;65:225-36.
24. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: A meta-analysis of prospective cohort studies. Am J Clin Nutr 2012;95:91-100.
25. Schöttker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev 2012 Feb 16. [Epub ahead of print]
26. Grant WB. Ecological studies of the UVB–vitamin D–cancer hypothesis; review. Anticancer Res 2012;32:223-36.
27. Lin SW, Wheeler DC, Park Y, Cahoon EK, Hollenbeck AR, Freedman DM, et al. Prospective study of ultraviolet radiation exposure and risk of cancer in the U.S. Int J Cancer 2012;131:E1015-23.

Competing interests: I receive funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), the Vitamin D Society (Canada), and the Sunlight Research Forum (Veldhoven).

William B. Grant, Independent researcher

Sunlight, Nutrition and Health Research Center, PO Box 641603, San Francisco, CA 94164-1603 USA

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We should like to thank William Grant’s comments on our article concerning the risks of exposure to artificial ultraviolet radiation.[1] His views certainly concur with those of the indoor tanning industry which has long claimed possible health benefits resulting from increasing one’s vitamin D health status to justify sunbed use.

Ecological and observational studies have found low vitamin D status to be associated with a wide diversity of conditions such as overall survival, multiple sclerosis, depression, cardiovascular diseases, hypertension, inflammatory processes, diabetes mellitus type 2, allergy and also rarer diseases.[2] However, ecological or observational associations by no means imply causality. To date, no randomised control trial of vitamin D supplementation has consistently shown that taking such supplements raising serum 25-hydroxyvitamin D levels above 20 or 30 ng/mL can prevent any chronic condition, including cardiovascular diseases, hypertension and diabetes.[3-8] Randomised trials have consistently failed to show that taking vitamin D supplements decreases the risk of breast or of colorectal cancer,[9-11] although changes in 25-hydroxyvitamin D level achieved in one of these trials (i.e., the Women’s Health Initiative study) were probably modest.[12] A key hypothesis to explain the discrepancy between observational and experimental studies would be the diversity of physiological functions of vitamin D in virtually all body organs. Low vitamin D status could be a reflection of metabolic disturbances found in patients with obesity, chronic inflammatory diseases, chronic heart failure, chronic kidney disease, particularly the bedridden, or those at the end of life.

In his commentary, WB Grant cites the Nebraska trial.[13] which suggested that supplementation with 27.5 µg per day of vitamin D3 could reduce the risk of cancer. However four letters to the Editor have significantly criticized the methodology and statistical analysis of this trial.[14-17] For instance, an intent‐to‐treat analysis comparing subjects receiving vitamin D with all subjects receiving calcium and/or placebo shows no significant decrease in cancer risk, whereas a significant decrease is observed when subjects receiving calcium supplements are compared with all subjects receiving vitamin D and/or placebo. Grant also cites a subgroup analysis of the Women’s Health Initiative study [18] whose results are incompatible with the analysis of the entire dataset.[19]

Some epidemiological findings on the extra-skeletal effects of vitamin D are worth consideration. For instance, meta-analyses and pooled analyses of randomised trials on vitamin D and calcium supplementation have found that elderly individuals taking these supplements were at reduced risk of all-cause mortality.[20-21] Additionally a prospective study of melanoma patients found that higher serum 25-hydroxyvitamin D levels were associated with a lower Breslow thickness at diagnosis and were independently protective of relapse and death.[22]

These findings may just be the result of other physiological disorders associated with greater propensity to develop advanced cancer, or to shorter survival. The observed effect of vitamin D and calcium supplementation on all-cause mortality may result from poor nutrition and metabolic decreases prevailing in many elderly. Nonetheless, these findings support the need to further investigate why vitamin D status seems to be associated with some key health events.

In contrast to the meagre data suggesting that normal healthy people need to increase their vitamin D status, a growing body of data indicates that long-term maintenance of high levels of 25-hydroxyvitamin D levels may be associated with shorter life expectancy.[3, 23] Furthermore, the Swedish Women's Lifestyle and Health cohort provided data suggesting for the first time that women regularly using sunbed could be at a higher risk of all-cause mortality and of cancer, especially of breast cancer.[24-25]

Our new meta-analysis incorporating more recent studies further strengthens the evidence on skin carcinogenic hazards associated with sunbed use.[26] In view of these health hazards and uncertainty about the benefits or risks of long-term maintenance of high vitamin D levels, recommending UV-exposure to prevent chronic diseases is not justifiable.

In some respect, the proposed worldwide epidemic of “vitamin D deficiency” affecting most healthy people can be regarded as a successful case of disease mongering.[27] The indoor tanning industry claims that acquiring a tan in a controlled environment is safe (or safer). However regulation of indoor tanning facilities does not change the real carcinogenicity of UV radiation.[28] The strategy of the indoor tanning industry has been described as similar to that of the tobacco industry[29] but ungrounded and deceptive statements about the positive health effects of indoor UV tanning should be strongly resisted. In France, advertisements claiming health benefit for consumers of indoor tanning parlours have already been banned.

Finally, for patients whose doctor determines their need to increase their vitamin D level, oral vitamin D supplements are widely available, and taking these supplements is cheaper and safer than indoor UV tanning.

References
1 Boniol M, Autier P, Boyle P, et al. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ 2012;345:e4757.
2 Harvey C. Vitamin D: some perspective please. BMJ 2012:345:e4695.
3 International Agency for Research on Cancer. Vitamin D and cancer. IARC Working Group Reports Vol. 5. Lyon: IARC, 2008. Available at: www.iarc.fr. accessed 26 July 2012
4 Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens 2009;27:1948–54.
5 George PS, Pearson ER, Witham MD. Effect D supplementation on glycaemic control and insulin resistance: a vitamin systematic review and meta-analysis. Diabet Med 2012;9:e142-50.
6 Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press, 2010. Available at: http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-an.... accessed 26 July 2012.
7 Sokol SI, Tsang P, Aggarwal V, et al. Vitamin D Status and Risk of Cardiovascular Events: Lessons Learned via Systematic Review and Meta-Analysis. Cardiol Rev 2011;19:192-201.
8 Gepner AD, Ramamurthy R, Krueger DC, et al. A prospective randomized controlled trial of the effects of vitamin d supplementation on cardiovascular disease risk. PLoS One 2012;7:e36617.
9 Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326:469.
10 Wactawski-Wende J, Kotchen JM, Anderson GL, et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006;354:684–96.
11 Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitaminD supplementation and the risk of breast cancer. J Natl Cancer Inst 2008;100:1581–91.
12 Autier P, Gandini S, Mullie P. A Systematic review: Influence of vitamin D Supplementation on serum 25-hydroxyvitamin D concentration. J Clin Endocrinol Metab Published Online First: Published online before print 14 June 2012. doi: 10.1210/jc.2012-1238
13 Lappe JM, Travers-Gustafson D, Davies KM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007;85:1586-91.
14 Sood MM, Sood AR. Dietary vitamin D and decreases in cancer rates: Canada as the national experiment. Am J Clin Nutr 2007;86:1549.
15 Bolland MJ, Reid IR. Calcium supplementation and cancer incidence. Am J Clin Nutr 2008;87:792-3.
16 Ojha RP, Felini MJ, Fischbach LA. Vitamin D for cancer prevention: valid assertion or premature anointment? Am J Clin Nutr 2007;86:1804-5.
17 Schabas R. Artifact in the control group undermines the conclusions of a vitamin D and cancer study. Am J Clin Nutr 2008;87:792.
18 Bolland MJ, Grey A, Gamble GD, et al. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011;94:1144–9.
19 Chlebowski RT, Pettinger M, Kooperberg C. Caution in reinterpreting the Women’s Health Initiative (WHI) Calcium and Vitamin D Trial breast cancer results. Am J Clin Nutr 2012;95:258-9.
20 Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1730–7.
21 Rejnmark L, Avenell A, Masud T, et al. Vitamin D with Calcium Reduces Mortality: Patient Level Pooled Analysis of 70,528 Patients from Eight Major Vitamin D Trials. J Clin Endocrinol Metab Published Online First: 17 May 2012. doi: 10.1210/jc.2011-3328
22 Newton-Bishop JA, Beswick S, Randerson-Moor J, et al. Serum 25-Hydroxyvitamin D3 Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma. J Clin Oncol 2009;27:5439-44.
23 Durup D, Jørgensen HL, Christensen J, et al. A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice, the CopD Study. J Clin Endocrinol Metab Published Online First: 9 May 2012. doi: 10.1210/jc.2012-1176
24 Yang L, Lof M, Veierød MB, et al. Ultraviolet Exposure and Mortality among Women in Sweden. Cancer Epidemiol Biomarkers Prev 2011;20:683–90.
25 Yang L, Veierød MB, Löf M, et al. Prospective Study of UV Exposure and Cancer Incidence among Swedish Women. Cancer Epidemiol Biomarkers Prev 2011;20:1358-67.
26 El Ghissassi F, Baan R, Straif K, et al. A review of human carcinogens—part D: radiation. Lancet Oncol 2009;10:751-2.
27 Moynihan R, Evan Doran, David Henry. Disease Mongering Is Now Part of the Global Health Debate. PLOS Med 2008;5:e106.
28 Autier P, Doré JF, Breitbart E, et al. The indoor tanning industry's double game. Lancet 2011;377:1299-301.
29 Greenman J, Jones DA. Comparison of advertising strategies between the indoor tanning and tobacco industries. J Am Acad Dermatol 2010;62:685.e1–18.

Competing interests: None declared

Mathieu Boniol, Research Director

Philippe Autier, Peter Boyle, Sara Gandini

International Prevention Research Institute, 95 cours Lafayette, 69006, Lyon, France

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The paper by Boniol and colleagues estimates that sunbed use accounts for 1096 (986-1224) cases of melanoma/year for men and 2341 (2107-2614) cases/year for women in 2008 [1]. The 95% confidence intervals were not stated but were calculated from the summary relative risk for ever use of sunbeds given in Table 2. A more important indication of melanoma risk is death from melanoma. The mortality rate can be estimated by the ratio of melanoma deaths to cases in the 27 countries of the European Union, available from GLOBOCAN [2]. Assuming that the EU-18 used in Ref. 1 account for 71% of both cases and deaths, there would be 186 (95% CI, 167-208) melanoma deaths for men and 304 (274-339) deaths for women in 2008. (See Table 1)

Any estimate of risk should also estimate benefit. This was not done in Ref. 1. Sunbeds are a good source of vitamin D, producing at least 10,000 IU in a single session [3]. There are about 15 types of cancer for which solar ultraviolet-B (UVB) irradiance has been found inversely correlated with incidence or mortality rate in ecological studies [4]. Vitamin D production is the only mechanism suggested to explain the findings. The role of vitamin D in reducing risk of cancer has been supported in observational [5,6] and randomized controlled trials [7,8].

An estimate of the benefits in reducing risk of internal cancers can be made using findings of cancer incidence in Sweden for women with respect to use of sunbeds [9]. Ref. 9 had information on sunbed use for 37,940 women. For the 26.2% of the women who used sunbeds rarely but not >1 time/month in any decade, 10-39 years, the hazard ratio for breast cancer was 0.81 (0.68-0.96) while that for overall cancer was 0.89 (0.79-1.00). These values were similar to those for annual number of weeks spent on sunbathing vacations, >1, 20-29 and/or 30-39 years: 0.87 (0.70-1.07) for breast cancer and 0.88 (0.77-1.01) for overall cancer, giving confidence in the findings.

The estimates for breast cancer and overall cancer can be estimated assuming that 16% of men and 26% of women used sunbeds in the amount used from Ref. 9 based on a study of sunbed use in Germany [10]. Breast cancer cases and deaths for the 18 European countries can be estimated from the data in Ref. 2 assuming that 71% of the cases and deaths are from the 18 countries included in Ref. 1. The estimate of reductions in cases in 2008 is 11,668 (19,652-3703) and that for deaths is 3151 (663-5307). (See Table 2.) For overall cancer, the estimates for reductions is 16,554 (0-31,602) cases and 8667 (0-16,547) deaths for men and 22,740 (0-43,414) cases and 11,265 (0-20,960) deaths. (See Table 3) The benefit-to-risk ratio based on overall cancer deaths to melanoma deaths is 47:1 for men and 37:1 for women. Since there are many other health benefits of vitamin D [11], the overall benefit-to-risk ratios are much higher.

There have been several papers reporting health benefits of sunbed use including higher bone mass density [12], reduced risk of thrombotic events [13], and reduced risk of endometrial cancer [14].

It should be noted that melanoma accounted for 1.2% of male cancer deaths in the European Union in 2008 and 1.1% of female cancer deaths [2]. Thus, to base sunbed use policy on melanoma when the health benefits are estimated to be large is not good public policy. It should also be noted that the role of UV in risk of melanoma is complex. Those who have chronic UV exposure do not have higher risk of melanoma than others [15-18].

An alternative source of vitamin D would be food fortification and easy access to high-dose (1000-5000 IU) vitamin D3 supplements. Vitamin D fortification of food in Europe is rare except in Nordic countries [19]. Vitamin D supplements are also hard to get. The fact that the IARC largely dismissed the evidence that vitamin D reduces the risk of cancer in 2008 [20] did not help. Some of the authors of Ref. 1 were involved in the preparation of the IARC report. The report was criticized for bias in evaluating the evidence that vitamin D reduced the risk of cancer [21]. The Institute of Medicine of the National Academies also largely dismissed the evidence in their 2011 review of vitamin D and calcium [22] since they were only willing to consider randomized controlled trials as strong evidence. This report has been criticized by over 140 peer-reviewed journal publications. As it is impossible to produce vitamin D for 3-6 months of the year in Europe [23], alternate sources of vitamin D are required, and sunbeds are such a source. The potential health benefits of vitamin D are very great as shown in ecological [15] and observational [11,24] studies and randomized controlled trials [25].

Returning to the analysis in Ref. 1, it should be noted that the analysis of risk of melanoma associated with ever use of sunbeds when first use was before age 35 years (Figure 1) has several problems not discussed by the authors of Ref. 1. One problem is that some of the studies did not adjust the findings for skin pigmentation [26]. Those with type 1 skin type have a much higher risk of melanoma than those with darker skin [27], and they are generally prohibited from sunbed use. A second problem is that several of the studies combined UV irradiance from three different sources: commercial tanning salons, home units, and medical facilities [28]. Risk of melanoma from home units might be higher than from tanning salons as home use is not regulated. A third problem is that the studies that reported an increased risk of melanoma with use of sunbeds prior to age 35 years were more likely to report statistically significant increased risk of melanoma with ever use of sunbeds [29]. Of the 15 studies used in the under 35-year analysis, six found statistically significant increased risk of melanoma for ever use of sunbeds. Of the 14 studies that did not provide results for those with first use prior to age 35 years, three reported statistically significant increased risk while one reported statistically significant reduced risk. Thus, the analysis is biased due to omission of data since the authors finding no correlation were not motivated to report the results for use prior to age 35 years.

Disclosure
I receive funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), the Vitamin D Society (Canada), and the Sunlight Research Forum (Veldhoven).

References
1.Boniol M, Autier P, Boyle P, Gandini S. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis. BMJ 2012;345:e4757.
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-917. http://globocan.iarc.fr/factsheet.asp
3. Moan J, Lagunova Z, Cicarma E, Aksnes L, Dahlback A, Grant WB, et al. Sunbeds as vitamin D sources. Photochem Photobiol. 2009;85:1474-9.
4. Grant WB. Ecological studies of the UVB–vitamin D–cancer hypothesis; review. Anticancer Res. 2012;32:223-36.
5. Grant WB. Relation between prediagnostic serum 25-hydroxyvitamin D level and incidence of breast, colorectal, and other cancers. J Photochem Photobiol B. 2010;101:130–6.
6. Grant WB. Effect of interval between serum draw and follow-up period on relative risk of cancer incidence with respect to 25-hydroxyvitamin D level; implications for meta-analyses and setting vitamin D guidelines, Dermatoendocrinol. 2011;3:199-204.
7. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586-91.
8. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Am J Clin Nutr. 2011;94:1144-9.
9. Yang L, Veierød MB, Löf M, Sandin S, Adami HO, Weiderpass E. Prospective study of UV exposure and cancer incidence among Swedish women. Cancer Epidemiol Biomarkers Prev. 2011;20:1358-67.
10. Schneider S, Zimmermann S, Diehl K, Breitbart EW, Greinert R. Sunbed use in German adults: risk awareness does not correlate with behaviour. Acta Derm Venereol. 2009;89:470-5.
11. Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr. 2011;65:1016-26.
12. Tangpricha V, Turner A, Spina C, Decastro S, Chen TC, Holick MF. Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D concentration) and higher bone mineral density. Am J Clin Nutr. 2004;80:1645-9.
13. Lindqvist PG, Epstein E, Olsson H. Does an active sun exposure habit lower the risk of venous thrombotic events? A D-lightful hypothesis. J Thromb Haemost. 2009;7:605-10.
14. Epstein E, Lindqvist PG, Geppert B, Olsson H. A population-based cohort study on sun habits and endometrial cancer. Br J Cancer. 2009;101:537-40.
15. Grant WB. An ecologic study of cancer mortality rates in Spain with respect to indices of solar UV irradiance and smoking. Int J Cancer. 2007;120:1123-7.
16. Chang YM, Barrett JH, Bishop DT, Armstrong BK, Bataille V, Bergman W, et al. Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls. Int J Epidemiol. 2009;38:814-30.
17. Newton-Bishop JA, Chang YM, Elliott F, Chan M, Leake S, Karpavicius B, et al. Relationship between sun exposure and melanoma risk for tumours in different body sites in a large case-control study in a temperate climate. Eur J Cancer. 2011;47:732-41.
18. Grant WB. Role of solar UV irradiance and smoking in cancer as inferred from cancer incidence rates by occupation in Nordic countries. Dermatoendocrinol. 2012;4(2) epub
19. Kiely M, Black LJ. Dietary strategies to maintain adequacy of circulating 25-hydroxyvitamin D concentrations. Scand J Clin Lab Invest Suppl. 2012;243:14-23.
20. IARC Working Group Report 5: Vitamin D and Cancer. IARC, Lyon, France (Nov. 25, 2008)
21. Grant WB. A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D. Dermato-Endocrinology. 2009;1:25-33.
22. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-8.
23. Webb AR, Engelsen O. Calculated ultraviolet exposure levels for a healthy vitamin D status. Photochem Photobiol. 2006;82:1697-703.
24. Schöttker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. Ageing Res Rev. 2012 Feb 16. Epub
25. Rejnmark L, Avenell A, Masud T, Anderson F, Meyer HE, Sanders KM, et al. Vitamin D with calcium reduces mortality: Patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab. 2012 May 17. Epub
26. Grant WB. Critique of the International Agency for Research on Cancer meta-analyses of the association of sunbed use with risk of cutaneous malignant melanoma. Dermatoendocrinol. 2009;1:294-9.
27. Bataille V, Boniol M, De Vries E, Severi G, Brandberg Y, Sasieni P, et al. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe. Eur J Cancer. 2005;41:2141-9.
28. Chen YT, Dubrow R, Zheng T, Barnhill RL, Fine J, Berwick M. Sunlamp use and the risk of cutaneous malignant melanoma: a population-based case-control study in Connecticut, USA. Int J Epidemiol. 1998;27:758-65.
29. Hoel D. IARC’s estimate of melanoma risk from sunbed use in young adults. Presented at the American Society for Photobiology conference in Montreal, June 26, 2012.

Competing interests: I receive funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), the Vitamin D Society (Canada), and the Sunlight Research Forum (Veldhoven).

William B. Grant, Independent researcher

Sunlight, Nutrition and Health Research Center, PO Box 641603, San Francisco, CA 94164-1603

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