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Peering Into Future
Cancer Prevention Becoming More Exact Science

By Rich McManus

On the Front Page...

If you thought that by maintaining ideal body weight, exercising, abstaining from tobacco, and eating plenty of fruits and vegetables that you were hewing to the latest wisdom in preventing cancer, think again. While these guidelines still apply, a new picture of cancer prevention is emerging that is much more particular and personal than the advice of the past: tailored interventions based on an individual's risk of cancer lie ahead, thanks largely to new methods of probing one's genetic makeup, said Dr. Bernard Levin, professor of medicine at the University of Texas M.D. Anderson Cancer Center.

Continued...

Giving the first annual Advances in Cancer Prevention Lecture — a new capstone to an NCI-sponsored academic course in cancer prevention and control that has been held for the past 15 years — Levin outlined a quantitative risk assessment method that takes into account specific tissue markers, epidemiological evidence, and genetic susceptibility markers that will allow clinicians to fine-tune treatments to individual profiles.

Dr. Bernard Levin

A standing-room-only crowd in Lister Hill Auditorium heard Levin bring into focus what NCI director Dr. Richard Klausner described as newly blurring margins between cancer treatment and detection; elements of both are embodied in the new science of prevention. But first Levin explained what's at stake: If you could eliminate all cancers completely with some new miracle compound, economic savings would be $46.5 trillion, according to economists at a Lasker Foundation symposium. If science could cure just one percent of all cancers, the savings would still be $500 billion, he noted.

As a model of an ideal prevention tool, Levin chose the hepatitis B vaccine. Introduced in Taiwan in 1985, it dramatically lowered incidence of the disease in that country. "Would that we had a vaccine against tobacco," he mused, showing slides projecting 450,000 tobacco-related deaths in the United States in 2000, and 3 million deaths worldwide.

He lamented the pervasive influence of tobacco in American life, quoting former FDA commissioner Dr. David Kessler's admonition that "tobacco is a pediatric disease." Levin said there is "an ominous increase in smoking" among ethnic minorities in 12th grade in Texas. "Moderate to substantial nicotine dependence was found in a majority of 850 teenagers sampled in Houston and Austin," he reported.

Gadgets as cumbersome as hand-held computers, programmed to schedule one's allowable smokes (in gradually decreasing increments), represent effective technology, Levin said. Descending to a smaller scale, he described the DRD2 A1 allele associated with heightened substance abuse and susceptibility to tobacco addiction as a valuable marker. Genes can help predict who will have trouble quitting smoking, and link that difficult effort to increased risk of alcohol abuse, substance abuse and depression.

Levin foresees, in the near future, 35 mm "blood slides" containing a single spot of blood that technology can sample perhaps 100 times over a period of many years and still get valuable genetic data. "You could store slides for an entire nation in a room this size," he said. Barcodes on the slide would identify whose DNA was stored there, and the process of sampling individual cards would be automated.

"Genetic ID cards are very much around the corner," he predicted.

He lauded NCI's launch of the Early Detection Research Network, a prevention effort based on molecular changes in tissue, and expects chemoprevention — the use of chemicals to reverse, suppress or prevent the carcinogenic process — to be effective. "There is a long period when screening and chemoprevention could make a difference in a variety of common epithelial cancers," he said.

Levin (l) accepts the first annual Advances in Cancer Prevention Lecture plaque from NCI director Dr. Richard Klausner.

In colon cancer, for example, there is a period of some 10 to 20 years when cells transform from normal to invasive. The enzyme cyclooxygenase-2 (COX-2) is elevated throughout this entire process, he said, and there is currently a promising trial showing that inhibition of this enzyme results in significant reduction of both tumor burden and size. "Overexpression of COX-2 is linked to several other premalignant conditions," he explained.

NCI is about to start a 12-year trial that will enroll some 32,400 men to investigate risk of prostate cancer. "It begins late this year, and will be the largest phase 3 trial ever undertaken," he said.

"The public is becoming very aware of cancer risk," he continued. "Web sites to evaluate your personal risk are proliferating (he showed a Harvard site entitled "What Is Your Risk?"), and the media are driving great interest in this subject (slides of Katie Couric, who lost her husband to colon cancer, on the cover of Time and McCall's, were shown). A new public hunger for screening is giving medicine a great challenge, he said.

He decried the rise of managed care, with its emphasis on cost-saving and impersonal doctor-patient relationships, as antithetical to a model proposed by the Institute of Medicine calling for "sustained partnerships" between patients and their physicians, particularly as data collection over time becomes more crucial.

Levin concluded his talk on an upbeat note for an audience composed, in part, of students aspiring to effective careers in cancer prevention: there are 14 cancer prevention academic programs, including his home institution, offering advanced training in this field.

During a brief question period preceding a reception for Levin, he returned to the devastation wrought by tobacco use in the U.S. "We don't seem to have the will to bring tobacco under control, despite the fact that it is the leading cause of cancer mortality, lung disease and heart disease. It would take a tremendous upheaval in the political and cultural process to turn things around — the forces are not yet powerful enough...There are no easy answers here."


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