When it comes to skin cancer, the sun, which is our best friendin some ways, may also be our worst enemy. The "healthy tan"that beach-basking vacationers flaunt and many weather-beaten outdoor workers acquire may in time presage theopposite of health -- basal-cell or squamous-cell carcinoma.
"Skin cancer is one of the commonest human cancers, and itsincidence is increasing," warns a paper in the currentProceedings of the National Academy of Sciences (PNAS) titled"UV and skin cancer: Specific p53 gene mutation in normal skinas a biologically relevant exposure measurement."
"UVB (ultra-violet-B) irradiance at the surface of the earth isalmost certainly increasing as a result of depletion ofstratospheric ozone," the paper adds. Its principal author,Hiroshi Yamasaki, notes that the methods and results hepresented to measure the relationship between UV exposureand skin cancer incidence will "improve our capacity to predictthe effects of, and respond appropriately to, UV irradiancechanges."
A cell biologist and biochemist, Yamasaki heads the Multi-StageCarcinogenesis Unit at the International Agency for Research onCancer (IARC) in Lyon, France. He told BioWorld that his unit'songoing research aims to predict as well as measure"biologically relevant UV exposure in our body. With whateverwe use or wear, we can reduce this UV mutation frequency." Headded: "We are not suggesting any particular behavioralchange, but these may be sought using our methods. Forexample, is sun-blocking cream protective enough or not? Thiswe can measure; there has been no other way to do so."
Ultra-violet radiation is both friend and foe to humans.Although it converts ergosterol to vitamin D and kills germs inthe air, UV radiation also kills epidermal cells in sunburnsufferers. It performs its helpful and harmful feats bydisrupting DNA in exposed tissues, whether human or microbe.If it weren't for the ozone shield, six to 30 miles up in thestratosphere, UV would destroy or severely damage virtuallyall life on the earth's surface.
Ozone, too, wears both white and black hats. An unstable,three-atom isotope of oxygen, this bluish gas is corrosive,explosive and toxic. As a 25-mile-thick layer enveloping earth'satmosphere, it keeps most UV radiation at a safe distance. Butnot as safe as it used to be.
Where Skin Color Really Counts
It's been 66 years since scientists determined that harmfulwavelengths of UV cause skin cancer. Not all populations are atequal risk. Most people carry in their skin deposits of thepigment melanin, the cellular equivalent of an ozone shield. Bydefinition, darker-skinned people can brave the sun longerthan fair-skinned people, who don't have enough melanin totan readily against the sun.
"Doctors can generally tell when a patient walks in that theyare at risk for skin cancer just on the basis of their phenotype,"said dermatological surgeon David Leffel of Yale University."We all see patients in practice who look as if they ought tohave a lot of skin cancer but don't, and vice versa." So Leffelwelcomes Yamasaki's research at IARC, aimed at a predictivetest of a given individual's genetic susceptibility.
Thus far that research, as reported in PNAS, has yielded thebeginnings of what Leffel's Yale colleague, biophysicist DouglasBrash, hailed as Yamasaki's "DNA direct exposure meter." Brashtold BioWorld, "It also measures cumulative lifetime exposure,and hopefully, in the future, how much sunlight it takes tocause how much cancer."
Research by Brash laid the groundwork for the IARC project. Hereported in 1991 that mutations in squamous-cell carcinomasof p53, a major tumor-represser, reflected switches of cytosineto thymine, or dimeric CC to TT, in the p53 genome.
To confirm the suspicion that UV radiation caused theseharmful alterations, Yamasaki compared skin biopsies fromoutdoor-type people in southwest Australia (among the world'ssunniest climes and probably located under a hole in the ozonelayer) with skin samples from French volunteers in oftencloud-covered Lyon.
The Australian skin-cancer clinic sent him frozen tissue fromnormal, non-cancerous skin taken from the shoulders(maximum solar exposure) and buttocks (minimum sunlight) of23 patients. Of these, 17 (74 percent) contained CC to TTtandem-base p53 mutations in the sun-exposed shoulder skin,but only one of 20 (5 percent) from the sun-shielded sites.
None of the French skin samples showed such genetic changes.
Yamasaki had previously implicated UV as the specificcarcinogenic agent by exposing cultured human epidermalkeratinocytes to an ultraviolet lamp with peak emission of 312nanometers. DNA amplification by both PCR and LCR (ligasechain reaction) detected CC to TT mutations in the cells' p53sequences.
Having demonstrated cause and effect in cells and living tissue,Yamasaki and his unit are now pursuing the ability to predictskin-cancer genetic risk in individuals with no sign ofmalignancy. "We are performing case-control studies withAustralian patients to see whether the biological markers weare using with the tumor suppresser gene is a real predictor ofcancer or not," he told BioWorld.
Leffel fervently looks forward to such a predictor. "A simpledoctor's office test that allows you to take a small sample ofskin and identify the people at risk who really need attentionand follow-up would be extremely valuable, especially in thisday of rationed health care," he said.
The Melanoma Connection
Yamasaki has other collaborative studies under way in Hawaiiand Italy to determine whether his method can be used toelucidate the unproved connection between melanoma andsunlight.
"The problem with melanomas is that they don't seem to havep53 mutations," said Brash. "The bet is that some other proteinbinds p53, and that's where the mutation is in melanoma, butnobody knows what gene encodes it."
Dermatologist Leffel, who supplies Brash with his skin biopsysamples, said, "It would not be surprising to find sun-inducedgenetic changes in melanoma." So if Yamasaki's predictivecapability pans out as a practical test, "it could prove also toisolate or highlight people with the greatest risk of melanoma,which is the most lethal form of skin cancer."
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.