Can Sunlight Help Prevent Skin Cancer?

Going out into the sun has become an act of war for many people. The sunscreen, hat, long sleeves - all are worn to ward off the sun's rays and protect against photo aging and skin cancer. But while the hazards of sun exposure are real, the sun may not be entirely the enemy some people think it is, says UCSF's Daniel D. Bikle, MD, PhD. He and fellow researchers at the San Francisco Veterans Administration Medical Center say that the vitamin D that sunlight helps the body create may help prevent a number of cancers, including skin cancer. "While the issue remains controversial in the scientific community, a growing body of scientific evidence suggests that just a little sun a day may be beneficial in warding off at least one form of skin cancer, squamous cell carcinoma, and, perhaps, other types of skin cancer as well," says Bikle, who is also professor of medicine and dermatology at UCSF. The findings appear in the December 2004 issue of the Journal of Nutrition. That the body needs sunlight to create vitamin D through a chemical reaction in skin cells is well established. Some epidemiologic evidence even suggests that inadequate vitamin D nutrition (which happens in part from too little sunlight exposure) is linked to colon, breast and prostate cancer. Bikle and other scientists say that sunlight's impact on vitamin D production may also help prevent some skin cancers. A form of vitamin D in the body triggers certain responses in cells that determine whether genes become active or inactive. Bikle and his VA Medical Center colleagues reviewed squamous cell carcinoma research from their lab and others. He notes that evidence suggests the findings could also apply to basal cell carcinoma, the most common form of skin cancer, and melanoma, a less common but often deadly form of the disease. Skin cancers are a serious problem. More than a million Americans develop skin cancer every year, making it the most common of all cancers. For some, it can be fatal. About 1,000 to 2,000 Americans die each year of squamous cell and basal cell carcinoma. The common squamous cell carcinoma is generally restricted to the upper levels of the skin. After some time, if not removed, it will penetrate the underlying skin tissue and, in a small number of cases, will metastasize, thus becoming life threatening. Basal cell carcinoma also emerges near the surface of the skin but its potential to metastasize is less than that of squamous cell carcinoma. Both diseases are distinct from melanoma, a less common form of skin cancer that involves skin cells known as melanocytes. Melonoma carries a much higher risk of metastasizing than the keratinocyte-derived basal and squamous cell carcinomas. Studying Skin In his laboratory at the VA Medical Center, Bikle and his colleagues study the complex biochemistry of the skin, the body's largest organ. He hopes the research will not only answer basic questions about the role of vitamin D in normal and cancerous skin cells, but also will lead to the development of a treatment for precancerous skin lesions, perhaps something as simple as a cream containing a form of vitamin D. "People who get one squamous cell carcinoma tend to get more, and those people may very well benefit from some form of therapy administered either topically or orally," Bikle says. The skin is organized into layers that constantly renew themselves. The basal layer contains stem cells whose role is to provide new cells for the upper layers. As the cells divide and rise to the skin's surface, they become more specialized. Genes turn on and off in these different stages of development, and the cells create various proteins in response to the genetic cues. The final product is a thick layer of cells rich with a protein called keratin to give the skin strength, bathed in fats to provide waterproofing. The outer layer eventually sloughs off as new cells move up from below. However, some skin cells fail to fully mature. Instead, their development stalls in an early stage and they divide unchecked, forming a cancer. Vitamin D is a hormone that occurs in several forms in the body. A form called 1,25(OH)2D3, also known as calcitriol, triggers biological responses in cells by controlling whether certain genes become active or inactive. Chain Reaction Sunlight sets off a cascade of reactions in the skin, culminating in the formation of calcitriol. Calcitriol enters the cell's nucleus, where it binds to its receptor to control the expression of genes that are vital to cell differentiation. These effects complement those of calcium, which indirectly controls gene expression by altering other signal molecules in the cell's cytoplasm. Two proteins intimately involved in this process, DRIP205 and SRC/p160, help activate the ability of calcitriol to regulate gene expression at different points in the cell's development cycle - DRIP at the beginning of differentiation, and SRC toward the end. But in squamous cell carcinoma, too much DRIP keeps SRC out of the picture, and these cells become resistant to the "differentiating" actions of calcitriol. This evolution of specialization occurs as the cells migrate upward through the various levels of the epidermis. "That is a critical concept in determining why vitamin D can't stimulate the differentiation of the [cancerous] cells," Bikle says. Researchers are trying to understand why cancerous cells never progress from making DRIP to making SRC. Much of this research has been done in cultured skin cells, which are a good model because they can be grown in culture dishes, sometimes partly exposed to air, duplicating the environment of intact skin. But research is also being performed on mice that lack some of the genes involved in calcitriol's action. For instance, mice without vitamin D receptors develop papillomas - wart-like precancerous growths that can progress to cancer - when exposed to chemicals that cause cancer. This effect happens at a much higher rate than in normal mice, and indicates that calcitriol has a protective effect against cancer. Under-nutrition But simply taking vitamin D in food doesn't seem to prevent skin cancers, although it may help protect against other cancers such as that of the breast, colon or prostate, Bikle says. However, more than half of Americans don't have vitamin D levels, which can be affected by sun-exposed skin or the diet that he and other scientists consider adequate. In hospital patients, that figure rises to more than 80 percent. "There's a great deal of vitamin D under-nutrition by these standards," he says. In the case of skin cells, directly applying calcitriol doesn't necessarily prevent cancer. At different dosages in cell culture, the vitamin can either prevent or promote the unchecked growth of cells, and its effects are also mixed depending on what chemical is used to trigger cancerous growth. But as the complex biochemistry becomes better understood, it may be possible to create chemically altered forms of vitamin D to prevent precancerous cells from becoming cancerous, says Bikle. "The key scientific question for me remains, what is the block in squamous cell carcinomas which prevents them from responding to vitamin D and calcium," Bikle says. In the meantime, the good feeling of the sun on your face is also healthful, as long as you don't overdo it: "Modest amounts of ultraviolet light are probably quite good for you in terms of making vitamin D," he says. Co-authors of the study were Yuko Oda, PhD, Zhongjian Xie, MD, PhD, and Chialing Tu, PhD., all of the San Francisco VA Medical Center. Tu also holds an appointment at UCSF. The study was supported by grants from the American Institute for Cancer Research, the National Institutes of Health, and a Veterans Affairs Merit Review Award. Source: Colleen Paretty