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In Reply

Department of Environmental Health, Harvard School of Public Health, Boston, MA

Rebecca S. Heist

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA

David C. Christiani

Department of Epidemiology, Harvard School of Public Health, Boston, MA

We do agree that "association does not mean causality," "physical activity and fitness are associated with vitamin D levels," and the existing data are not powerful enough to draw any conclusion or make any recommendation regarding the use of vitamin D supplementation as adjuvant therapy for lung cancer. Therefore, results from this epidemiologic study need to be confirmed and validated by other observational studies as well as by randomized clinical trials. However, we do not believe that "vitamin D should be considered just a marker of physical fitness," for a number of reasons. First, many studies have reported that dietary/supplemental vitamin D intake is associated with favorable prognosis of various types of cancers,^2,3 and this association cannot be explained by physical fitness alone. Second, studies have also suggested that vitamin D receptor polymorphisms may be associated with prognosis of various types of cancers.^4-7 Third, physical fitness/activity may explain only some of the effects of vitamin D in lung cancer prognosis. Other vitamin D determinants include season of diagnosis, residential region/latitude.^8-12 These have been shown consistently to be associated with lung cancer prognosis, and are not necessarily associated with physical fitness. Fifth, the hazard ratios and P values for overall survival and disease-free survival are similar in our report, especially for the joint effects of circulation 25-hydroxyvitamin D levels and vitamin D intake. Sixth, in vitro and animal assays support the biologic mechanism of vitamin D in the prognosis of lung cancer.^13-15 Additional research is needed to define the clinical utility of vitamin D in lung cancer treatment.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

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1. Reference deleted

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7. Obara W, Suzuki Y, Kato K, et al: Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population. Int J Urol 14:483-487, 2007[CrossRef][Medline]

8. Zhou W, Suk R, Liu G, et al: Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Cancer Epidemiol Biomarkers Prev 14:2303-2309, 2005[Abstract/Free Full Text]

9. Lim HS, Roychoudhuri R, Peto J, et al: Cancer survival is dependent on season of diagnosis and sunlight exposure. Int J Cancer 119:1530-1536, 2006[CrossRef][Medline]

10. Grant WB: The likely role of vitamin D from solar ultraviolet-B irradiance in increasing cancer survival. Anticancer Res 26:2605-2614, 2006[Medline]

11. Porojnicu AC, Robsahm TE, Dahlback A, et al: Seasonal and geographical variations in lung cancer prognosis in Norway: Does Vitamin D from the sun play a role? Lung Cancer 55:263-270, 2007[CrossRef][Medline]

12. Grant WB: An ecologic study of cancer mortality rates in Spain with respect to indices of solar UVB irradiance and smoking. Int J Cancer 120:1123-1128, 2007[CrossRef][Medline]

13. Maeda Y, Hirai T, Yamato H, et al: Antitumor effect of 24R,25-dihydroxyvitamin D3. In Vivo 2:129-132, 1988[Medline]

14. Higashimoto Y, Ohata M, Nishio K, et al: 1 alpha, 25-Dihydroxyvitamin D3 and all-trans-retinoic acid inhibit the growth of a lung cancer cell line. Anticancer Res 16:2653-2659, 1996[Medline]

15. Nakagawa K, Sasaki Y, Kato S, et al: 22-Oxa-1alpha,25-Dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer. Carcinogenesis 26:1044-1054, 2005[Abstract/Free Full Text]

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