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

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

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

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.
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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.
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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: No competing interests

27 July 2012
Mathieu Boniol
Research Director
Philippe Autier, Peter Boyle, Sara Gandini
International Prevention Research Institute
95 cours Lafayette, 69006, Lyon, France