Ways to Reduce Cancer Risk

By Judith Paley, MD

Skin cancer is not just a matter of being one sunbeam over the line. Scientists are discovering ever more about the road between the initiating event and the development of a tumor, and it's marked by ravaged DNA, cellular repair mechanisms gone bad, and the wild proliferation of a brotherhood of mutant cells. Every step of the way presents opportunities for cancer prevention: avoid initiation (don't tan, don't smoke, etc.), promote cellular repair (selenium, aspirin, grape juice, and green tea to name a few), and avoid stimulation to cellular division (e.g. suppress ovulation, use care with post-menopausal estrogen). This week's edition examines a small part of this enormous body of knowledge, particularly the role of p53, one of the body's most important defenses against cancer.

This information is intended to be general in nature and should not be relied upon for specific treatment. If you need medical attention, please contact your personal physician's office for an appointment.

No such thing as a safe tan

Next time you head out in search of some color from a "safe" tanning salon, stop at the drugstore for self-tanning goo instead. In exchange for a free series of ten full-body UV treatments, a group of sun-loving volunteers underwent biopsies f sites that seldom see the light of day. These skin samples roved that sunlamp-roasted DNA does not fare well.

The researchers analyzed the bits of buttocks for cyclobutane yrimidine dimer (CPD for short) and p53 protein. CPD is the most common type of DNA damage caused by ultraviolet radiation. This altered DNA causes the body to produce p53 protein, a benevolent molecule which either prevents cellular reproduction while the damage is repaired or kills off cells too far gone to salvage. Analysis of the well-tanned derrieres showed significantly increased levels of both CPD and p53 within 24 hours of the first tanning session. A single 15-minute exposure was as bad as ten sessions and provided as much UV wattage as an entire day at the beach!

In addition, sunlamps emit mostly UVA radiation which penetrates the skin more deeply than the UVB rays from sunlight, accelerating aging and wrinkling. Says Baltimore's Dr. Whitmore, "A suntan is the skin's response to an injury; every time you tan, you accumulate damage to the skin."

If you've overindulged in sun worshipping when young and foolish (did you use those aluminum reflectors to even tan the skin under your chin?), beware the actinic keratosis (AK). These scaly little heaps of sun-damaged skin can transform over time into bad-news lesion called squamous cell carcinomas. AK's, variably colored pink, red, brown, or flesh, are commonly found on such sun-exposed areas as hands, forearms, face, ears, and the shiny top of a bald man's head. They can either regress on their own, persist as benign, or progress to cancer.

Treatment is indicated for multiple or changing AK's, particularly in older individuals with lots of sun-damaged skin. A useful treatment for AK's and small basal cell cancers is imiquimod cream (brand name Aldara). Originally developed to treat genital warts, this cream promotes an immune response when applied to sun-damaged skin lesions which calls on the body's own defense mechanisms to take out the abnormal cells.

Have you thanked your p53 today?

Hats off then to our plucky little p53 genes that stop mutant cells dead in their tracks. As noted above, the p53 protein (product of p53 genes) protects against DNA damage by halting the normal cell reproduction cycle or by inducing cellular suicide. Increased levels of p53 protein indicate a cellular repair process is underway and is found not only in sun-damaged skin, but in the cheek cells of heavy smokers.

The search is on for chemopreventive agents that may promote the production of p53. Rats who were treated with selenium, vitamin C, and vitamin E prior to lapping up some horrific arcinogenic chemical demonstrated more p53 and less breast tumors than their furry friends in the vitamin-free control group.

What if, however, the p53 gene is the hapless victim of a wayward sunbeam or a crazed free radical? If just one chromosomal copy is taken out, no problem, the cell still self-destructs. If both copies are rendered dysfunctional, the cell-line expands rather than dies, and this uncontrolled proliferation of cells with mutant p53 is the most frequent genetic alteration seen in human cancers. Not only do such cells lose tumor suppressor activity, the gummed-up p53 can actually promote tumor cell growth, increase tumor blood supply, and increase resistance to chemotherapy and radiation. The presence of mutant p53 proteins within tumors predicts more aggressive cancers in the skin, lung, breast, and ovary.

Constant ovulation increases cancer risk

Mutant p53 genes (see above) are a common theme in multiple tumors, and ovarian cancer is no exception. Evidence of abnormal p53 protein is present in half of all ovarian cancers, and these are the most aggressive ovarian tumors. Researchers at Duke University have discovered a biological link between such cancers and the number of times a woman ovulates over her lifetime. "When a woman ovulates, the egg that is extruded from the ovary blows a hole in the surface of the ovary," notes Dr. Andrew Berchuck. The more a woman's ovarian surface explodes and repairs with ovulation, the higher the probability that a spontaneous mutation will occur in the p53 gene.

If a woman ovulates without interruption for 38 reproductive years, she has nearly 500 lifetime ovulatory cycles (LOC). The investigators defined "high LOC" as 376 or more, and women with p53-positive tumors were 9 times as likely to have big-time LOC's. Epidemiological studies have already shown that suppression of ovulations by breast-feeding, pregnancy, and birth control pills decreases the risk of ovarian cancer.

Green tea preserves DNA of mice and men

Green tea cream protects sun-bathing mice from sun-damaged skin (and that leathery, aging mousy look). At the rodents' request, researchers also discovered that black tea lapped up by mouth or smeared on the fur inhibited the heaped-up scaly skin that's a hallmark of too much time spent by the laboratory pool. In further reassuring news for the volunteers, black or green tea prevented the accumulation of p53 proteins, a known molecular marker for sun-stressed skin cells.

Now green tea anti-oxidants have been taken into the human realm, applied in a cream form to that well-known sun-protected site (a favored research focus because of its lack of accumulated sun damage). Brave human volunteers not only exposed their back-ends to ultra-violet light, they then allowed researchers to nick a sample of skin. On examination, these skin shards showed that green tea decreased ultraviolet-induced DNA damage. Supplementation of skin-care products with green tea may prove to be a new weapon against skin cancer.

Dr. Paley welcomes comments and questions at her femailhealthnews@aol.com address. For more information about her free weekly newsletters on women's health, go to www.femailhealthnews.com.