More than 1.2 million cases of non-melanoma skin cancer are diagnosed each year in the United States. Most of them are the result of sun exposure, but HSPH and Dartmouth researchers are finding that other exposures-for example to certain medications or chemicals in drinking water-are also playing a significant role.
“Excess sun exposure is by far the biggest contributor to skin cancer risk, but it is not the only thing,” said Heather Nelson, Assistant Professor of environmental epidemiology in the Department of Environmental Health, who is conducting a study on these exposures with Margaret Karagas of Dartmouth Medical School.Their research is based in New Hampshire, which is a low-sun exposure region. They are looking at the effects of certain medications, including immune suppressive drugs and birth control pills, as well as arsenic in drinking water and the use of tanning beds, on incidence of basal cell and squamous cell carcinomas, both of which are non-melanoma skin cancers. While these types of skin cancers are rarely fatal if excised, the collective cost of removal places a large financial burden on the Medicare program, Nelson said. And removal of these cancers, which are often found on the face, can be disfiguring.The NIH-funded study, which began in 1993, is tracking every case of skin cancer in New Hampshire, with blood samples collected from more than 2,000 cases. Nelson’s lab at HSPH is running genetic tests on the samples, looking for common genetic variations that may make people more or less susceptible to skin cancers.Nelson said that the use of oral steroids for various medical conditions, including asthma, seems to be strongly linked to skin cancer development. She noted that organ transplant recipients, who must take heavy doses of steroids to prevent rejection, routinely come down with numerous skin cancers. Even patients taking low doses of steroids have double the skin cancer risk, she said. Further, her group has identified a genetic variant that results in a five-fold increased risk of skin cancer associated with use of glucocorticoids, a class of steroids that reduce inflammation in conditions such as arthritis.She speculated that the steroids, which lower the immune system response, allow skin cells that have been altered by the sun, for example, to grow into cancers.Another co-exposure that contributes to skin cancer appears to be arsenic in drinking water, she said. The carcinogenic chemical can be found in moderate to high levels in unfiltered water from private wells in the U.S. In New Hampshire, about 40 percent of residents are supplied with their drinking water from private wells. “We know from areas with very high exposure, such as Bangladesh, that the skin is very much affected by arsenic exposure,” Nelson said. “Arsenic alters the expression of genes in cells, decreasing their ability to repair DNA damage,” she explained. “The arsenic exposure prevents the skin cells from dealing with sun-induced damage, essentially increasing the adverse effects of sunlight.”One of Nelson’s recent graduate students, Katie Miller, was investigating the impact of birth control pill exposure on skin cancer risk. Whether this link is the result of the hormones impacting the immune system or because they simply cause cells to proliferate and divide faster is not known, Nelson said. Miller is now a research fellow in the Department of Genetics and Complex Diseases.It turns out that these non-solar exposures are more likely to cause squamous cell carcinomas than those of the basal cell variety, according to Nelson, and this may be related to the cellular origin of the tumour. Basal cell carcinomas derive from stem cells, and this may offer them some protection from these non-solar exposures. Using genetics testing on the tumours themselves, the Nelson lab has found that squamous cell carcinomas may actually be further divided into two varieties, based on genetic mutations. One type carries an alteration in a gene called ptch, which is important in the part of the tissue where stem cells live. These squamous cell carcinomas with a ptch mutation seem to have a similar risk factor profile to that seen in basal cell carcinomas. However, those squamous cell carcinomas with the intact ptch gene are more susceptible to the risks of non-solar exposure.Being able to differentiate these squamous cell carcinoma types may help predict the risks associated with various types of exposures, she said.For example, exposure to tanning beds poses the greatest cancer risk for tumours with the ptch gene deleted, while exposure to steroids carries a 4.4-fold increased risk to squamous cell carcinomas with a normal ptch gene. Exposure to oral contraceptives poses a 5.4-fold increased risk to such cells.”This stem cell marker is an important tool for classifying squamous cell carcinomas to better understand non-solar risk factors,” Nelson said. “We think this is going to be very helpful in moving forward with policy debates as it allows a better estimate on exposures that can be regulated, such as arsenic in drinking water or medications such as contraceptives or glucocorticoid steroids.”(Source: Harvard Public Health: July 2006).