Effect of vitamin D receptor genotype on the relationship between sun exposure and melanoma risk

February 1, 2008

There is growing evidence that vitamin D "protects" us against colorectal, breast and prostate cancers. According to a recent study in patients with multiple primary and primary single melanomas, chronic daily sun exposure may be more beneficial than harmful in that it contributes to a great extent to vitamin D synthesis.

Key Points

Albuquerque, N.M. - Vitamin D is an integral part of the status quo and homeostasis in our bodies, and irreplaceable with regard to regulating body levels of calcium and phosphorus, as well as in the mineralization of bone in sync with sun exposure. A recent study shows that this vitamin may play an important role in protecting against an array of cancers, including malignant melanoma.

"One of the things we are interested in is the effect of sun exposure on the skin, and the development of melanoma and survival of melanoma patients. We think that vitamin D may play a key role in this relationship.

"This is why we looked at polymorphisms and the vitamin D receptor, which is essential for the utilization of vitamin D," says Marianne Berwick, Ph.D., M.P.H., professor and chief of the division of epidemiology at the University of New Mexico.

Dr. Berwick and a team of researchers conducted a multicenter study from nine different population centers in North America, Europe and Australia, analyzing the vitamin D receptor genotype on the relationship between sun exposure and the development of melanoma in patients with multiple primary and single primary melanomas.

In a preliminary study of 2,126 study participants, 1,301 had a history of a primary melanoma and 825 had a history of multiple primary melanomas.

Patients were required to give a very detailed residential history and a very detailed sun exposure history over a lifetime, as well as to submit a DNA sample.

Dr. Berwick tells Dermatology Times that an SNP (single nucleotide polymorphism) is a variation in the gene, and it is normal that we have endless variations in our genetic structures due to evolution.

Upon analyzing two of the many vitamin D receptor polymorphisms (or SNPs), Dr. Berwick and her team noticed that there was a very interesting relationship with chronic sun exposure among people who had these SNPs.

Everyone has three possible genotypes. One is the wild type (bb), which is the normal; that is, without any change. Then, there is a heterozygous form (Bb). This genotype has just one small change at a specific allele within the gene. The third genotype is the variant form, also called homozygous mutant form or minor allele, and this genotype has two different alleles than the wild type.

A significant protective effect of recent daily sun exposure was seen with the BB genotype. No significant effects were seen with either the Bb or bb genotypes. People with FF have low risk of developing melanoma, and people with ff - the homozygous mutant - have an increased risk with sun exposure, especially with multiple melanomas.

"We saw that if people had a lot of sun exposure and they had any alterations in one of these SNPs, they had less risk of developing melanoma," Dr. Berwick says.

Dr. Berwick says that these experiments evaluating polymorphisms and vitamin D and the importance of vitamin D are still in "early days."

She says there is a lot of controversy about what vitamin D does with regard to its comprehensive effect with sun exposure, how much sun exposure is needed in order to have enough vitamin D, and whether we should increase vitamin D in our diets or take vitamin D supplements.

"At this point of our research, we are simply not sure. We do not know if it is really vitamin D that is imparting protection against ultraviolet radiation and melanomas, as well as protecting us against other cancers, such as colorectal, breast and prostate cancers, although more and more evidence is mounting to suggest precisely this," Dr. Berwick says.

According to Dr. Berwick, there is a new suggestion among some experts that sun exposure prior to the diagnosis of melanoma may also be somewhat protective against the development of melanomas.

She says sun exposure may somehow act as an adjuvant therapy by inhibiting cell proliferation and increasing apoptosis and causal mutations.

"Our study is just a piece of this great puzzle; however, we are coming closer. The Genes and Environment in Melanoma (GEM) study as a whole will have almost twice as many study participants, from whom we will have a lot of information on more SNPs and on more variants within the vitamin D receptor.

"In our study, we were able to see the relationship between sun exposure and SNPs, and it is a clear step forward in helping us to focus our efforts further," Dr. Berwick says.

She says this study offers physicians more evidence that vitamin D, or the genetic pathway for the metabolism of vitamin D, may be important and protective in the area of melanoma.

However, the research is in the early stages, and according to Dr. Berwick, it is important to follow this up with rigorous studies.

"Sun exposure is self-regulating, but sun exposure also has risks of squamous and basal cell carcinomas, as well as melanomas. But you will never get toxic from the vitamin D you get from sun exposure.

However, a number of experts in the Northeast part of the U.S. - where there is not very much sunshine - suggest taking supplements of vitamin D," Dr. Berwick says.