A combination of calcium and vitamin D may slash the risk of melanoma in half for some women at high risk of developing this life-threatening skin cancer.

Using existing data from a large clinical trial, the study narrowed in on women with a history of nonmelanoma skin cancer, because individuals with this typically nonfatal disease are more likely to develop the more deadly illness--melanoma. Researchers, from the Stanford University School of Medicine (Stanford, CA, USA), discovered that women who once had nonmelanoma and took the calcium/vitamin D combination developed 57% fewer melanomas than women with similar histories who were not given the supplements. Nonmelanoma skin cancers, such as basal cell or squamous cell tumors, are the most common forms of skin cancer.

“In preventive medicine, we want to target people most at risk for the disease,” said dermatologist Jean Tang, MD, PhD, lead author of the study. “If you previously had a nonmelanoma skin cancer, calcium, plus vitamin D might reduce your risk of the more deadly melanoma.”

Dr. Tang added a note of caution. The study revealed that a daily dose of 1,000 mg calcium plus 400 IU of vitamin D does not provide skin cancer protection for everybody. Women without a history of nonmelanoma skin cancer who took the supplements did not see any reduction of risk compared with their placebo-group counterparts, according to the research. The study’s findings were published online on June 27 in the Journal of Clinical Oncology.

Vitamin D is well known for its role in bone growth, but it also affects nonskeletal cells. In many parts of the body, including the skin, vitamin D controls how quickly cells replicate, a process that frequently goes amiss in cancer. Reports from various institutions have suggested that vitamin D is linked with lower risks of colon, breast, prostate, and other cancers. Nevertheless, the Institute of Medicine (Washington DC, USA) published a report in November 2010 stating that more research was needed on vitamin D and calcium, as the evidence was inadequate to validate their having a benefit for conditions other than bone health.

This study is the second to examine the effect of vitamin D supplementation on cancer risk with a randomized, controlled trial.

Dr. Tang and colleagues analyzed data from the Women’s Health Initiative (WHI), a study that followed 36,000 women ages 50 to 79 for an average of seven years. Half of the women took the daily dose of calcium and vitamin D as part of the experiment; the other half took a placebo pill. The WHI calcium plus vitamin D trial was designed to look at the effects of the supplement on hip fractures and colorectal cancers, but its researchers collected data on many other health issues, including other cancers.

Dr. Tang and colleagues took advantage of the large and long-term data set provided by the WHI trial to explore whether vitamin D has a protective effect against skin cancer. “Our results include the first positive cancer-reducing effect seen from the calcium plus vitamin D trial,” said Teresa Fu, MD, a coauthor of the study and a recent graduate of the School of Medicine.

The lack of protective effect in women without a history of nonmelanoma skin cancer may be due to the amount of vitamin D given to the patients in the WHI trial. “The patients in the Women’s Health Initiative were given vitamin D at a very low dose, based on today’s knowledge --only 400 IU per day,” said David Feldman, MD, professor emeritus of endocrinology and a coauthor of the study. Furthermore, patients in the placebo group were allowed to take as much vitamin D as patients that were provided the calcium and vitamin D supplements, so the experimental difference between the two groups was small. In light of that small difference, “it’s somewhat surprising that there was an effect on melanoma risk, and I think many potential benefits of vitamin D may not have been detected,” said Feldman.

Because men were not included in the trial, the researchers cannot be sure whether the protective effect of the supplements would also apply to men with a history of nonmelanoma skin cancer. Nonetheless, a 2010 study by Dr. Tang showed that elderly men with higher blood levels of vitamin D have fewer nonmelanoma skin cancers.

Even in a large study like the WHI, the low frequency of melanomas means that the absolute number of cancers was small. Out of the 36,000 participants, only 176 cases of melanoma were reported. “That just highlights how large a trial needs to be to capture cancer as relatively rare as melanoma,” said Marcia Stefanick, PhD, the Stanford WHI lead investigator and senior author of this study.

“These results spur us to do more studies,” said Dr. Tang. She is planning multiple lines of research to study the possible relationship between vitamin D and cancer prevention, including research that will compare blood levels of vitamin D with melanoma outcomes. Another phase of study will examine the effect of larger doses of vitamin D on the behavior of skin cells in patients with high skin-cancer risk.

Guangzhou Jia Yu medical equipment Limited