BOSTON-Excessive sun exposure is a known risk factor for the development of skin cancer, but sun exposure appears to have a protective effect against a variety of other cancers, according to speakers at a symposium on sunlight at the 168th National Meeting of the American Association for the Advancement of Science (AAAS).
BOSTONExcessive sun exposure is a known risk factor for the development of skin cancer, but sun exposure appears to have a protective effect against a variety of other cancers, according to speakers at a symposium on sunlight at the 168th National Meeting of the American Association for the Advancement of Science (AAAS).
Sunlight’s product, vitamin D, long recognized as crucial to a number of vital bodily functions, also protects against prostate, breast, and colon cancer, and probably other solid tumors, said panel member Michael F. Holick, PhD, MD, professor of medicine, dermatology and physiology and director of the Vitamin D, Skin and Bone Research Laboratory, Boston University School of Medicine. In agreement was William B. Grant, PhD, an independent scholar from Newport News, Virginia.
Dr. Holick cited physiological evidence and Dr. Grant presented data from an ecological study to argue that insufficient vitamin D is related to higher cancer incidence and mortality.
Kenneth Kraemer, MD, research scientist in dermatology at the National Cancer Institute, however, reminded the audience that sunlight is clearly implicated in the genetic damage leading to basal cell and squamous cell carcinoma and, to a lesser extent, melanoma.
The link between cancer protection and vitamin D is the enzyme 25 hydroxy vitamin D 1-hydroxylase, Dr. Holick said. This enzyme is vital for changing the inactive form of vitamin D, produced when the skin reacts to sufficient sunlight, into the activated form that can be used by cells. Among other functions, he noted, activated vitamin D appears to down-regulate cell growth, acting as a "brake" on incipient cancers.
The hormone was previously thought to occur only in the kidney. It is now known, however, that prostate, breast, skin, and colon tissue also produce it, Dr. Holick said. He suspects that it also occurs in other tissues as well. A variety of organs thus have the ability to take circulating vitamin D and turn it into the activated form, he noted.
Sunlight and Cancer Rates
Studies have shown that animals deficient in vitamin D have more metastatic cancer than animals whose vitamin D levels are adequate, he said. Although the incidence of skin cancer in humans is directly correlated with sun exposure, he said, it is inversely correlated with the incidence of prostate, breast, and colon cancers. Indeed, he said, the incidence of these and some other solid tumors is higher in high latitudes where sunlight is scarce and people do not receive enough sunlight to maintain adequate levels of vitamin D.
Dr. Grant presented data amplifying this point. He showed the results of comparisons between the amounts of sunlight received in various parts of the United States and the geographic variation in the incidence of cancers of the breast, colon, rectum, prostate, bladder, gallbladder, kidney, corpus uteri, and esophagus (see also Grant WB: Cancer 94:272-281, 2002 and 94:1867-1875, 2002).
Vitamin D can also be obtained from food, Dr. Grant said, but diet cannot be responsible for the differences in cancer rates among American regions because diet is very similar in the nation’s four quadrants. The major explanatory factor, Dr. Grant said, is the difference in ultraviolet-B (UVB) radiation received from sunlight by people in different regions. Residents of the South and Southwest receive more UVB radiation than those in the northern parts of the country because the more southerly regions have more sunny days and receive sunlight at less oblique angles.
In addition, he said, many parts of those regions are higher in elevation and less urban than the north, thus having less of the air pollution that also cuts down on UVB rays.
Residents of the sunnier regions produce more vitamin D in their bodies, and also produce it for much more of the year. In places as far north as Boston, Dr. Holick noted, people do not receive enough sunlight to maintain adequate vitamin D levels without also receiving the vitamin from food or supplements.
Dr. Grant compared the death rates of various cancers in high-sunlight and low-sunlight regions of the United States and calculated what he terms "excess cancer deaths"deaths that would not have occurred if people in sunlight-poor regions had received adequate vitamin D. His estimates range from 5,000 excess colon cancer deaths and 4,000 excess breast cancer deaths a year to 130 excess kidney cancer deaths. The total he says, tops 23,600 annually.
Although Dr. Grant admits that "ecologic study [of cancer causality] is always suspect," he believes that "sort of like a jury trial . . . the preponderance of evidence" proves his assertion. No other factor explains the geographic distribution of cancer in the United States, he said. Although cancer rates (other than lung cancer) have changed over recent decades, the relative cancer rates of the various regions have not changed.
Despite the purported protective effect of sunlight in some cancers, Dr. Kraemer countered, the relationship between the cell damage caused by sunlight and the occurrence of basal cell and squamous cell skin cancers is well established.
UVB radiation causes a "signature mutation" in the p53 gene, which is implicated in a number of cancers, including skin. Damage may also occur elsewhere in the genome, he said, noting that "not many genes have been examined" for these effects.
To demonstrate the connection, Dr. Kraemer cited studies of patients with xeroderma pigmentosum, a rare skin condition that causes defects in the cells’ molecular machinery for making nucleotide repairs by excision.
This autosomal recessive condition causes a 1,000-fold increase in skin cancers, including in such unusual places as the tip of the tongue, and also eye and other cancers. In addition, 20% of patients with the condition experience neurological degeneration.
Xeroderma pigmentosum patients, who number several hundred in the United States, essentially have no means of repairing the genetic damage caused by UVB rays, Dr. Kraemer said. They experience skin cancer 50 years earlier than individuals with normal cellular repair mechanisms, who have an average age of onset of 60.
More than 90% of the squamous cell carcinomas and more than 50% of the basal cell carcinomas in persons with xeroderma pigmentosum show the "fingerprint of UVB damage," namely the characteristic p53 mutation, he said. There is also damage on a newly discovered gene involved in cellular repair through patching, he added.
It is therefore clear that both basal and squamous cell skin cancer are related to sunlight, Dr. Kraemer said. The incidence of both shows a direct relationship with regional variation in sunlight. The relationship between sunlight and melanoma is less strong, he added, noting that "the problem is that we don’t know the mechanism of melanoma induction."
Dr. Holick emphasized that despite the important role of vitamin D in regulating cell growth, it cannot be used for treating frank cancers. Vitamin D and, by extension, sunlight exercise their protective effects very early in the process of cancer development.
To benefit from this protective effect, people need far more vitamin D than most receive, Dr. Holick said. A moderate amount of sunlight is advisable throughout the year, he stated, and Dr. Kraemer concurred, stressing the word "moderation." In the absence of sufficient sun exposure, Dr. Holick recommends that healthy people receive supplementation amounting to 1,000 units of vitamin D per day, which is much higher than generally recommended.