Thirteen-year-old Jeff Markway finally got around to showing his mother the golf ball–sized lump on his right arm. He demonstrated for her how the lump would move up and down when he wiggled his right thumb. Not surprisingly, Jeff’s mother was alarmed by what she saw and rushed her son to the doctor. At first their doctor was not concerned because he thought the lump was simply a cyst, a fluid-filled hollow and not a serious problem at all. When the doctor attempted to drain the cyst, however, instead of finding fluid in the lump, the doctor observed that it was filled with cells. The lump was not a cyst at all; it was cancer. In fact, the tumor formed because Jeff had melanoma, a particularly invasive and deadly skin cancer. How could a 13-year-old develop melanoma—or any cancer, for that matter?
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Jeff and his family were referred to Dr. Henry Lynch, a physician and scientist whose specialty was the study of genetic factors important in cancer. Jeff was diagnosed with Xeroderma pigmentosum (XP), a rare disorder in which people are extremely sensitive to ultraviolet light (UV) and develop skin cancers more easily if they are exposed to sunlight or other sources of UV light. Lynch examined Jeff’s entire family and found that his sisters Patrice and Kathleen, and his twin brothers Phil and Gregg, all had XP. In fact, of the seven siblings of the Markway family, five suffered from the disease. XP affects only 1 out of every 250,000 people, and yet most of the Markway children had it. Clearly there is a genetic component to this disorder.
Individuals with XP who are under the age of 20 years have a 2000-fold higher incidence of skin cancer than those without XP. Also, the median age of skin cancer for individuals with XP is 8 years, while the median for individuals without XP is 58 years. Evidently, XP increases the sensitivity of skin to sunlight and speeds up the process whereby UV light exposure causes skin cancer.
Dr. James Cleaver learned of the Markway family’s extreme sensitivity to UV light from an article he read in the newspaper. Interested in the effects of UV radiation on DNA, Cleaver eagerly contacted Dr. Lynch to see whether it would be possible to study their cells. They willingly agreed.
Cleaver’s study unlocked the secret of exactly what went wrong in XP. Normal cells exposed to UV radiation experience DNA damage, but the cells are able to repair it. In XP cells, the UV damage to DNA is permanent. The cells are incapable of doing DNA repair. Consequently, the UV-exposed XP cells accumulate DNA damage, some of which renders the cells more likely to become cancerous. Affected individuals must avoid sunlight and UV light completely. Many go outdoors only at night.