Scientific Priorities for Cancer Research: NCI's Extraordinary Opportunities

Research on Tobacco and Tobacco-Related Cancers

Goal

The Opportunity

• Tobacco use causes more premature death than do all drugs of abuse combined.
• Lung cancer, which is estimated to account for approximately 157,400 deaths in 2001, would be a rare disease in the absence of smoking.
• Cancers of the mouth, pharynx, larynx, esophagus, pancreas, cervix, kidney, and bladder are all associated with tobacco use.

• Addiction to nicotine drives the continued use of tobacco even when the user is fully aware of increased risk of disease and premature death. Some people will continue to smoke even as they undergo treatment for a life-threatening disease.



• Tobacco-related diseases such as lung cancer remain some of the most difficult to treat effectively.

• Why children and adults use tobacco.
• How they become addicted.
• Why those who become addicted have such difficulty quitting.
• How to prevent, detect, and treat cancers caused by exposure to tobacco and its constituents.

Tobacco and Tobacco-Related Cancers: Good News and Bad

• Comprehensive state/community tobacco control programs work. For example, Arizona's adult tobacco use dropped from 23 percent in 1996 to 18 percent in 1999.
• Smokers do want to quit. Approximately 39 percent of all adult smokers made an attempt to quit in the past year.
• Consumption of cigarettes continues to decline, dropping from 4,345 per capita in 1963 to 2,146 per capita in 1999.
• Lung and bronchus cancer deaths are estimated to drop from 158,700 in 1996 to 157,400 in 2001, primarily due to decreased smoking.

• Youth smoking increased from 28 percent in 1991 to 35 percent in 1997 although it has since declined somewhat.
• Those with the least education and income smoke the most: 11 percent of college graduates smoke compared with 34 percent of those who did not finish high school.
• Lung cancer now kills approximately 157,400 people each year in the U.S. alone. It would seldom occur if people did not smoke.

Progress in Pursuit of Our Goal

• New evidence is helping to better explain why some people are more vulnerable than others to DNA damage caused by tobacco exposure.



• Research on the early detection of lung cancer suggests that it may soon be possible to identify cancers in smokers and former smokers at a much earlier and more treatable stage.



• Recent studies of teen smokers have identified psychological factors that increase the risk of becoming addicted, as well as the need to provide younger smokers with specialized programs to help them quit.



• A new evidence-based guideline, which NCI helped to develop, enables healthcare providers to offer smokers practical, effective strategies to quit smoking. If applied widely, this could have a dramatic effect on the number of smokers who successfully quit.



• Also, new cancer treatments based on molecular targeting provide models for how to increase the effectiveness of therapies for tobacco-related cancers.

• A chemoprevention and biomarker study involving lung cancer survivors and patients at high risk for lung cancer is underway. Strategies include the use of drugs, vitamins, or other agents to reduce the risk or delay the development or recurrence of cancer. Investigators in the Lung Cancer Biomarkers and Chemoprevention Consortium began recruiting patients in the summer of 2001 to participate in two trials evaluating chemopreventive drugs.


Researchers will perform biomarker analyses on tissues obtained during the studies and correlate these findings with patient outcomes. Three of NCI's Specialized Programs of Research Excellence (SPOREs) in lung cancer are participating in these trials as well as other institutions.


• The Lung Cancer Screening Study began in 2000 to assess the feasibility of the spiral computed tomography (CT or CAT) scan to detect early lung cancers. As of the spring of 2001, 3,300 people were randomized to either a spiral CT or a chest x-ray at six screening centers across the country. Investigators are:
• Comparing the lung cancer detection rates.
• Measuring how much and what kind of medical follow-up is needed
• Tracking how frequently participants receive spiral CT scans outside the study.

Although spiral CT scans are advertised as a new way to find early lung cancer in both current and former smokers, questions remain unanswered regarding its risks and benefits making these results crucial for the design of larger, more definitive studies. The study builds on the infrastructure of the NCI-supported Prostate, Lung, Colorectal, and Ovarian screening trial, launched in 1992 to examine whether annual chest x-rays, which are easier to perform than the spiral CT scans, can reduce mortality from lung cancer.


• Through two new initiatives begun in the summer of 2001, NCI will fund preclinical and clinical studies to identify newer, more potent agents that may prevent cancers in former smokers. Currently, almost half of all new cases of lung and bladder cancer occur in former smokers. It is vitally important to identify molecular and imaging markers of cancer risk and abnormal and uncontrolled cell growth and to test agents that can prevent the development of cancer in this group.

• The Prostate, Lung, Colorectal, and Ovarian screening trial is examining:
• Emphysema in relation to smoking.
• How genetic factors influence smoking.
• The differences between current and former smokers regarding genes that might be involved in nicotine dependency.

This information will prove increasingly precious over time as cancer cases develop in the cohort and their biospecimens become available for special study.


• Through an NCI-supported study of a group of women in Shanghai, we have an unprecedented opportunity to prospectively collect data and biospecimens from both non-smoking women who are exposed to second-hand smoke and their husbands who tend to be active smokers. Similarly, we have incorporated major biospecimen collections into studies that compare groups of people with cancer to healthy control groups. Specific studies initiated during the past year focused on smoking-related cancers such as lung, bladder, and renal cancers.



• NCI supports regional biorepositories, such as the expanded Frederick Biorepository and the Cooperative Human Tissue Network, which fill a critical need by housing and maintaining human biospecimens such as tissue, blood, and urine. Scientists collect these biospecimens from large-scale studies and make them available to researchers.

• In June 2001, NCI brought together more than 200 investigators from across the country to share the latest scientific evidence concerning tobacco use among youth. Their research indicates that both social influences and inherited factors are predictors of youth tobacco use.



• A recent study of fifth- and eighth-grade students from New England middle schools showed that students who view more tobacco use in movies are more likely to try smoking.



• Studies of twins show that inherited factors influence whether a person will smoke and how difficult it will be to quit.

• TTURC research has shown that smokers with a unique genetic makeup started smoking almost two years earlier than others. Investigations of genes important in smoking have focused on the dopamine system and on the brain chemical serotonin, which plays a role in depression and anxiety, both traits associated with smoking.



• Another study has assessed factors associated with high school students' decisions to smoke. High academic performance, perceived academic competence, and involvement in school-related clubs and sports teams were found to decrease the risk of smoking, while alcohol or marijuana use and novelty-seeking were associated with increased smoking.



• Another TTURC study is examining factors that affect the progression of smoking initiation and use among youth of diverse cultures. Early results of this research suggest that the patterns of smoking initiation in the United States and China are similar and that the optimal age for smoking prevention interventions is between 10 and 15, earlier than many of the programs aimed at youth currently start.

• Understanding the genetic factors related to nicotine initiation and dependence will be critical to the development of new medications to help smokers quit. With NIDA, NCI created a working group to advise both Institutes on key areas where progress can be achieved in the development of new medications for smoking cessation.



• NCI has supported innovative smoking cessation interventions that are tailored to the unique needs of individual smokers. For example, one recent study found that an "expert system" intervention, which provided computer-assisted feedback and help, resulted in quit rates that were almost 33 percent higher than for those without it. Conducted in a health care system, this study opens the door for increased assistance to smokers in environments where maximum medical follow-up is possible.



• A recent study funded through the NCI SPOREs initiative showed that those smokers who carried the DRD2-A1 genotype were more likely to relapse than those who carried the DRD2-A2 genotype, suggesting the possibility of developing tailored approaches to treatment that take into account unique genetic traits.

• The dose-response impact of specific toxins found in tobacco smoke.
• What type of smokers will choose harm reduction products over quitting.
• The potential for such products to decrease the desire to quit smoking.

• Surveillance of the changing global patterns of tobacco use.
• Development of scientific and public health networks to optimally address tobacco control.
• Development of interventions for preventing and treating tobacco use.

• Partnered on a Global Youth Tobacco Survey led by the Centers for Disease Control and Prevention to document and monitor the prevalence of and contributing factors of youth tobacco use.



• Contributed to the design and funding of a new research initiative led by the NIH Fogarty International Center that will support international tobacco and health research as well as capacity-building efforts and studies that emphasize tobacco control research in low- and middle-income countries.



• Initiated a new lung cancer study in Milan, Italy, to evaluate gene-environment interactions in the development of lung cancer. This study includes the genetics of nicotine addiction and the treatment of smoking dependence.

The Plan - Research on Tobacco and Tobacco-Related Cancers

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