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Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study

Andreas Seidler, Gaël Paul Hammer*, Gabriele Husmann, Jochem König, Anne Krtschil, Irene Schmidtmann and Maria Blettner

Journal of Occupational Medicine and Toxicology 2008, 3:12  doi:10.1186/1745-6673-3-12

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Cancer incidence ecological study in Rhineland-Palatinate, Germany, provides strong support for the ultraviolet B–vitamin D–cancer hypothesis

William B. Grant   (2010-07-19 11:50)  Sunlight, Nutrition, and Health Research Center (SUNARC) email

The paper by Seidler et al. [1] provides strong support for the ultraviolet B–vitamin D–cancer hypothesis [2-5]. This study was designed to look for a potential association between pesticide exposure and cancer risk. By dividing the state into three categories, (small: >0 to 5 percent; medium: >5 to 20 percent; large: >20 percent area under wine cultivation), the study essentially divided the state into urban, mixed, and rural regions. It is reasonable to expect that those living in the rural region would have greater solar ultraviolet (UV) irradiance, and, based on the standardized incidence ratios (SIR) for non melanoma skin cancer (NMSC) and malignant melanoma for men shown in Table 4, that seems to be the case. The situation is not as clear for women as shown in Table 5, but those living in the urban regions had lower skin cancer and malignant melanoma SIR than those living in the mixed or rural regions.

As has been discussed in several papers, NMSC incidence and mortality rates serve as an index of solar UVB irradiance experienced by individuals and the population [6-11]. While the effect is stronger at latitudes equatorward of about 40º [9,10], there is evidence that the effect is also observed at higher latitudes in Europe [8,11]. Risk factors for melanoma include both UVA and UVB; with sunscreen use at high latitudes, UVA is the more important risk factor while for lower latitudes, sunburning from UVB is more important [12].

The role of solar UVB in reducing the risk of cancer can be estimated from the results in Tables 4 and 5. For this, I will assume that the lower 95% confidence interval (CI) for NMSC and malignant melanoma should be higher than the upper 95% CI interval for other cancers for the mixed or rural regions. For males, the cancers that satisfy this criterion for both regions are: stomach; colon, sigmoid & rectum; trachea, bronchus and lung; urinary tract; leukaemia; and all malignancies excluding C44. For females, the cancers that satisfy this criterion for both regions are: stomach; colon, sigmoid & rectum; trachea, bronchus and lung; cervix uteri; and ovary and other unspecified female genital organs. All of these cancers have been identified as having reduced risk from solar UVB in one or more ecological studies [5, 7, 13, 14].

However, puzzling is why some well-studied vitamin D-sensitive cancers did not show inverse correlations. For males, the reduced SIR was not statistically significant. Bladder cancer is vitamin D sensitive [5], but also sensitive to pesticides. Risk for prostate cancer is hypothesized to be linked to genetics and diet rather than vitamin D [15]. For non-Hodgkin’s lymphoma for both males and females, the SIR was significantly reduced in one region but not the other. Other studies have found NMSC correlated with risk of lymphoma [16]; however, at least in sunny countries, there is a benefit for UVB irradiance [17]. For females, the SIR for breast cancer was not significantly reduced. Alcohol is a risk factor for breast cancer [18], and in an affluent, wine-growing county in California, alcohol consumption is a risk factor for breast cancer [19]. The SIR for corpus uteri cancer was higher than for NMSC, malignant melanoma. Alcohol is also a risk factor for this cancer [20]. Thus, increased alcohol consumption in the winegrowing regions might explain these findings.

To extend this study, serum 25(OH) levels could be measured in summer for a cross-section of the older population living in each region.

In terms of policy, it would be worthwhile to recommend raising serum 25-hydroxyvitamin D levels to above 100 nmol/L at the population level, a value estimated to reduce all-cause mortality rates by 15-20% and health system costs by 10-15% [21-25]. In the absence of solar UVB, it would take 2000-5000 IU/day of vitamin D3 (cholecalciferol) to achieve this goal since each 1000 IU/day increases serum 25-hydroxyvitamin D levels by 15-25 nmol/L [26].

References
1. Seidler A, Hammer GP, Husmann G, König J, Krtschil A, Schmidtmann I, Blettner M. Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study. J Occup Med Toxicol. 2008 Jun 6;3:12.

2. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980;9:227-31.

3. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252-61.

4. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: Global perspective. Ann Epi. 2009;19:468-83.

5. Grant WB, Mohr SB. Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Ann Epidemiol. 2009;19:446-54.

6. Grant WB. A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers. J Steroid Biochem Mol 2007;103:668-74.

7. 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.

8. de Vries E, Soerjomataram I, Houterman S, Louwman MW, Coebergh JW. Decreased risk of prostate cancer after skin cancer diagnosis: A protective role of ultraviolet radiation? Am J Epidemiol. 2007 165: 966-972.

9. Tuohimaa P, Pukkala E, Scelo G, Olsen JH, Brewster DH, Hemminki K, Tracey E, Weiderpass E, Kliewer EV, Pompe-Kirn V, McBride ML, Martos C, Chia KS, Tonita JM, Jonasson JG, Boffetta P, Brennan P. Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: Vitamin D as a possible explanation. Eur J Cancer. 2007;43:1701-12.

10. Grant WB. The effect of solar UVB doses and vitamin D production, skin cancer action spectra, and smoking in explaining links between skin cancers and solid tumours. Eur J Cancer. 2008;44:12-15.

11. Soerjomataram I, Louwman WJ, Lemmens VE, Coebergh JW, de Vries E. Are patients with skin cancer at lower risk of developing colorectal or breast cancer? Am J Epidemiol. 2008;167: 1421-9.

12. Gorham ED, Mohr SB, Garland CF, Chaplin G, Garland FC. Do sunscreens increase risk of melanoma in populations residing at higher latitudes? Ann Epidemiol. 2007;17:956-63.

13. Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993-2000. BMC Cancer. 2006;6:264.

14. Grant WB. Does Solar Ultraviolet Irradiation affect Cancer Mortality Rates in China? Asian Pac J Cancer Prev. 2007;8:236-42.

15. Grant WB. A multicountry ecological study of risk-modifying factors for prostate cancer: Apolipoprotein E 4 as a risk factor and cereals as a risk reduction factor. Anticancer Res. 2010;30;189-99.

16. Adami J, Frisch M, Yuen J, Glimelius B, Melbye M. Evidence of an association between non-Hodgkin's lymphoma and skin cancer. BMJ. 1995;310:1491-5.

17. Kricker A, Armstrong BK, Hughes AM, Goumas C, Smedby KE, Zheng T, Spinelli JJ, De Sanjose S, Hartge P, Melbye M, Willett EV, Becker N, Chiu BC, Cerhan JR, Maynadie M, Staines A, Cocco P, Boffeta P; for the Interlymph Consortium. Personal sun exposure and risk of non Hodgkin lymphoma: A pooled analysis from the Interlymph Consortium. Int J Cancer. 2008;122:144-54.

18. Grant WB. An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates. Cancer. 2002;94:272-81.

19. Keegan TH, Chang ET, John EM, Horn-Ross PL, Wrensch MR, Glaser SL, Clarke CA. Recent changes in breast cancer incidence and risk factor prevalence in San Francisco Bay area and California women: 1988 to 2004. Breast Cancer Res. 2007;9:R62.

20. Friberg E, Orsini N, Mantzoros CS, Wolk A. Alcohol intake and endometrial cancer risk: a meta-analysis of prospective studies. Br J Cancer. 2010;103:127-31.

21. Grant WB, Cross HS, Garland CF, Gorham ED, Moan J, Peterlik M, et al. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in Western Europe. Prog Biophys Mol Biol. 2009;99:104–13.

22. Grant WB. In defense of the sun: An estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin D levels were raised to 45 ng/mL by solar ultraviolet-B irradiance. Dermato-Endocrinology, 2009;1:207–14.

23. Grant WB, Schwalfenberg GK, Genuis SJ, Whiting SJ. An estimate of the economic burden and premature deaths due to vitamin D deficiency in Canada, Molec Nutr Food Res. 2010 Mar 29. [Epub ahead of print]

24. Grant WB, Schuitemaker G. Health benefits of higher serum 25-hydroxyvitamin D levels in The Netherlands. J Steroid Biochem Molec Biol. 2010 Apr 14. [Epub ahead of print]

25. Zittermann A. The estimated benefits of vitamin D for Germany. Mol Nutr Food Res. 2010 Apr 1. [Epub ahead of print]

26. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204-10.

Competing interests

I receive or have received funding from the UV Foundation (McLean, VA), the Sunlight Research Forum (Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Danish Sunbed Federation.

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