NOORDWIJK, NETHERLANDS — Vitamin D supplementation was protective against late relapse of melanoma, particularly among patients who carry certain polymorphisms of the vitamin D receptor, Dr. Julia Newton Bishop reported at a conference on melanoma sponsored by Imedex Inc.
“In recent years there has been considerable interest in vitamin D because of its diverse functions, including antiproliferative and antiangiogenic effects,” Dr. Newton Bishop said.
The observation of the vitamin's effect on melanoma relapse emerged from a case-control study that included 143 patients who relapsed more than 3 years after surgical removal of their primary tumor, and 189 patients matched for age, sex, and Breslow thickness who did not relapse.
“Our hypothesis was that relapses and deaths within the first 3 years are likely to be related to the genetic and epigenetic effects of the tumor,” she said. Later relapses, in contrast, may relate to environmental effects on persisting melanoma cells.
Study participants filled out a questionnaire on dietary habits, vitamin supplementation, and sun exposure history. Serum and DNA were obtained to test for two known functional vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs), Cdx-2 and FOKl, and three noncoding SNPs, Apal, Bsml, and Taql, that have been shown to be associated with altered levels of VDR expression.
Data analysis revealed that there were no differences between cases and controls with regard to overall dietary practices or Fitzpatrick skin types.
Nor were there differences in time spent sunbathing or in the number of reported sunburn episodes either before or after diagnosis.
Although more relapsing patients reported using sunblock after the removal of their tumor than controls—91% vs. 85%—this difference was not statistically significant, said Dr. Newton Bishop of the Genetic Epidemiology Division, Cancer Research U.K., St. James's University Hospital, Leeds, England.
However, there were significant differences in vitamin D supplement use during the year prior to relapse, with 42% of controls and 28% of relapsing patients reporting that they took supplementary vitamin D. The odds ratio was 0.54 for relapse among those with a history of vitamin D supplement use, she said.
Serum vitamin D levels were significantly higher in those taking the supplement than in those who did not: a mean level of 54.3 nmol/L compared with 42.8 nmol/L. These measures confirmed patients' reports of taking the vitamin, she said.
VDR genotype results were available for 300 of the participants. None of the SNPs showed a significant association with relapse overall, but among patients who carried one or more copies of the variant Cdx-2 allele for increased VDR activity and expression, supplement use was associated with a highly significant reduced risk of relapse, with an odds ratio of 0.1.
Among patients who were homozygous for the wild-type variant of Taql associated with increased expression of VDR, there also was a significant reduction in risk of relapse, again with an odds ratio of 0.1.
“The observed protective effects of vitamin D intake and interaction with VDR genotype suggest that [this vitamin] is an important therapeutic candidate, which must be urgently evaluated further,” she said.