Cancer Prevention

1998-1999

Significant research findings about chemoprevention and nicotine addiction reported last year from M. D. Anderson faculty are helping advance the science and application of cancer prevention.

“Based on these and other ongoing studies, we are moving closer to the time when our recommendations for reducing individual risk for cancer will be better supported by data obtained through multidisciplinary research,” observes Dr. Bernard Levin, vice president for cancer prevention and holder of the Betty B. Marcus Chair in Cancer Prevention.

Largely through research conducted for more than a decade at M. D. Anderson, chemoprevention has emerged as a promising approach to halt the development of certain cancers — and in some instances to reverse premalignant changes. Encouraging results have been described from studies of synthetic vitamin A derivatives (retinoids), calcium, aspirin and several natural compounds.

During the past year, physicians and scientists in the Division of Cancer Prevention increased their collaboration with colleagues from the Department of Thoracic/Head and Neck Medical Oncology and other disciplines to document the role of chemoprevention. Many cancer prevention faculty also work closely with experts at other institutions.

One of the year’s highlights came last spring when findings from an extensive National Cancer Institute-funded tamoxifen clinical trial were announced. The study involving 13,388 women at high risk for breast cancer showed a 49 percent reduction in incidence of the disease. Of 270 study sites, M. D. Anderson enrolled more participants (300) than any other center. This investigation involved researchers from Clinical Cancer Prevention and Breast Medical Oncology.

“My colleagues and I are encouraged because data obtained during the tamoxifen study gives additional credence to the idea that cancer can be prevented. We are also excited about other chemoprevention studies focusing on head and neck, lung, bladder, prostate, skin and colon cancers,” says Dr. Scott M. Lippman, chairman of the Department of Clinical Cancer Prevention. He holds the Margaret and Ben Love Professorship in Clinical Cancer Care in honor of Dr. Charles A. LeMaistre.

Another landmark study that identified a genetic component for nicotine addiction was published by Dr. Margaret R. Spitz, who chairs the Department of Epidemiology and holds the Olga Keith Wiess Chair for Cancer Prevention.

Dr. Spitz and her collaborators demonstrated individual variants in receptors for the brain chemical dopamine among 157 newly diagnosed lung cancer patients and 126 healthy control subjects. They found a higher level of inherited rare dopamine receptor genes correlated with patients who had tried but been unable to quit smoking.

Dopamine, the brain chemical responsible for pleasureable feelings, is a neurotransmitter that helps relay messages between nerve cells in the brain. The M. D. Anderson study suggests that individuals with the genetic differences may derive more pleasure from smoking than those without the inherited markers, thus providing a biological explanation for why nicotine addiction is so hard to overcome.

“Findings such as these give us the long-term hope of developing targeted chemical interventions for smokers most vulnerable for nicotine addiction. By interrupting the addictive process, we have new opportunities to prevent lung cancer and other diseases caused by cigarette smoking,” Dr. Spitz says.

Other promising research ongoing in the Department of Epidemiology includes the study of:

• Newly diagnosed lung cancer patients who are current or never smokers to determine whether genetic links are present in their susceptibility to the disease. In a related study, epidemiologists and others are investigating lung cancer susceptibility in former smokers.
• Susceptibility to ultraviolet radiation-induced cancers. Researchers are ascertaining whether or not an association exists between DNA repair capacity and the risk of developing aggressive basal and squamous cell skin cancer.
• Brain tumors that may involve a hereditary component. Scientists are examining the exent to which genetics contribute to brain tumor development. This is the largest ever family study of malignant gliomas.

Important information has been gained in the past year by Department of Behavioral Science faculty, whose research focuses on how and why people smoke and testing potentially better ways to help them stop. Considerable data also is being generated through innovative quality-of-life studies about breast, ovarian and prostate cancers.

One project directed by Dr. Ellen R. Gritz, who chairs the department, strives to understand factors associated with smoking initiation among multi-ethnic youth. She wants to develop culturally appropriate educational methods to prevent adolescents and teens from starting to smoke. Earlier studies showed that white and Hispanic youths are more likely to begin smoking than their African-American counterparts.

“Tobacco use claims more than 430,000 lives in the United States each year. Smokers who die often are replaced by youths who start smoking, so we must increase our efforts to keep them from ever smoking and to convince those who have to quit,” says Dr. Gritz, holder of the Annie Laurie Howard Research Professorship.

Related projects to help any-age smokers stop involve hand-held computers that offer personalized messages for each smoker. These studies aim to interrupt smokers’ conditioned responses to environmental cues and remind them of the dangers of smoking.

Dr. Paul M. Cinciripini, who heads M. D. Anderson’s Tobacco Research and Treatment Program, was the lead author last year in a major collaborative report that included updated health policy recommendations from prominent physicians and scientists long involved in smoking control issues.

Among their findings:

• From 33 to 50 percent of people who smoked only one cigarette became addicted.
• Addiction to nicotine is more widespread than alcohol, cocaine and heroin use.
• High school students had an increase of smoking from 27.5 to 34.8 percent during a four-year period.
• The average age of smoking initiation and smokeless tobacco use was under 15.

Research at M. D. Anderson’s Science Park-Research Division in Smithville adds to the understanding of what causes cancer and tests methods that may prevent the disease. Many studies are conducted in collaboration with colleagues in Houston. Dr. John DiGiovanni is  ad interim  director of the Research Division and holds the Ruth and Walter Sterling Professorship.

Some productive projects at the Research Division aimed at learning the fundamental processes of cancer-causing agents, called carcinogens, include:

• Animal studies showing that high concentrations of coumarins, which are chemicals found in citrus fruits, may inhibit induction of skin cancer linked to benzo(a)pyrene, a tobacco carcinogen. This work could lead to chemoprevention strategies for skin cancer.
• New findings illustrating that calorie restrictions can delay spontaneous cancer development in mice who lack the p53 tumor suppressor gene. Such studies suggest that restricting calories may have broad inhibitory effects on some forms of human cancers.
• Ongoing research demonstrating that selective estrogen receptor modulators (SERMs) could be effective in treating uterine leiomyoma, a common gynecologic tumor. This is the first pre-clinical study that has shown potential therapeutic application of SERMs for uterine leiomyoma.