Originally published as JCO Early Release 10.1200/JCO.2009.22.1135 on September 21 2009

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Serum 25-Hydroxyvitamin D₃ Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma

Julia A. Newton-Bishop, Samantha Beswick, Juliette Randerson-Moor, Yu-Mei Chang, Paul Affleck, Faye Elliott, May Chan, Susan Leake, Birute Karpavicius, Sue Haynes, Kairen Kukalizch, Linda Whitaker, Sharon Jackson, Edwina Gerry, Clarissa Nolan, Chandra Bertram, Jerry Marsden, David E. Elder, Jennifer H. Barrett, D. Timothy Bishop

From the Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds; Department of Dermatology, University Hospital Birmingham National Health Service Foundation Trust, Birmingham, United Kingdom; and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.

Corresponding author: Julia A. Newton-Bishop, MD, Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, St James's Hospital, Beckett St, Leeds LS9 7TF, United Kingdom; e-mail: j.a.newton-bishop{at}leeds.ac.uk.

Purpose A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma.

Methods A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma. We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort (median follow-up, 4.7 years).

Results In the retrospective study, self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse (odds ratio = 0.6; 95% CI, 0.4 to 1.1; P = .09). Nonrelapsers had higher mean 25-hydroxyvitamin D₃ levels than relapsers (49 v 46 nmol/L; P = .3; not statistically significant). In the cohort (prospective) study, higher 25-hydroxyvitamin D₃ levels were associated with lower Breslow thickness at diagnosis (P = .002) and were independently protective of relapse and death: the hazard ratio for relapse-free survival (RFS) was 0.79 (95% CI, 0.64 to 0.96; P = .01) for a 20 nmol/L increase in serum level. There was evidence of interaction between the vitamin D receptor (VDR) BsmI genotype and serum 25-hydroxyvitamin D₃ levels on RFS.

Conclusion Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome. The cohort study tests this hypothesis, providing evidence that higher 25-hydroxyvitamin D₃ levels, at diagnosis, are associated with both thinner tumors and better survival from melanoma, independent of Breslow thickness. Patients with melanoma, and those at high risk of melanoma, should seek to ensure vitamin D sufficiency. Additional studies are needed to establish optimal serum levels for patients with melanoma.

S.B., J.R.-M., and Y.-M.C. contributed equally to this work.

Supported by the following: The collection of samples in the melanoma cohort study was funded by Cancer Research UK (project Grant No. C8216/A6129 and program award C588/A4994) and by the National Institutes of Health (Grant No. R01 CA83115). Recruitment was facilitated by the UK National Cancer Research Network. The relapse study was funded by Cancer Research UK (Programme Grant No. C588/A4994). It was also in part funded by a grant from the Skin Cancer Research Fund, Frenchay Hospital, Bristol, United Kingdom.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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