Re: Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis
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).
Rapid Response:
Re: Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis
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).