Lung and Other Tobacco-Related Cancers
On this page:
- Tobacco-Related Cancers
- Biology
- Risk Factors
- Prevention and Control
- Early Detection, Diagnosis, and Prognosis
- Cancer Control, Survivorship, and Outcomes Research
Lung cancer is the leading cause of cancer death for men and women in the United States, claiming the lives of an estimated 157,200 people in this country each year. The average annual rate of invasive lung and bronchus cancer among American women between 1995 and 1999 was 51.4 per 100,000. It is estimated that lung cancer will affect 80,100 women in 2003 and approximately 68,800 will die from lung cancer. Although incidence and mortality rates in men have been declining since the late 1980s, these rates for women continued to increase into the 1990s, leveling off since 1991 for incidence and 1995 for mortality.
Since 1987, more women have died each year of lung cancer than of breast cancer, which until that year had been the major cause of cancer death in women for more than 40 years. High lung cancer mortality rates reflect our limited ability to detect lung cancer at an early and potentially more curable stage. Through the use of available detection methods, most people are diagnosed in advanced stages of the disease, and only 15 percent survive for 5 years. Survival improves dramatically, to 49 percent, when the disease is identified and treated early.
Smoking, a preventable factor, has been implicated in many cancers of concern to women including: lung, cervical, breast, endometrial, and ovarian. NCI has taken the lead in a public/private partnership effort to address the high rate of tobacco-related cancers in women. A meeting, held in February 2003, Women, Tobacco, and Cancer: An Agenda for the 21st Century, assembled researchers, clinicians, and members of the advocacy community to identify gaps and research priorities, and to identify and prioritize needs in dissemination and application. Recommendations from that meeting will provide the basis for the development of action plans to increase our understanding of the sex-based differences in women's smoking behaviors, susceptibility to tobacco addiction and tobacco-related cancers, and translation of current knowledge to effective prevention and treatment interventions.
NCI's Lung Cancer PRG released a report in August 2001 that assessed the state of the science and recommended future research-related priorities for lung cancer. The PRG recommended the implementation of interdisciplinary, multi-institutional consortia; emphasized the need for continued research on the genetic, social, and biobehavioral aspects of tobacco control; and the need to better elucidate the contributions of injury, inflammation, and infection on lung cancer development.
Transdisciplinary Tobacco Use Research Centers (TTURCs). Launched in 1999 under the joint sponsorship of NCI, the National Institute on Drug Abuse, and the Robert Wood Johnson Foundation, TTURCs are helping to provide the needed infrastructure for tobacco research across many disciplines. TTURC researchers are tackling a wide range of topics, including genetic susceptibility, animal models of behavior, sociocultural factors, innovative treatments, and research on health care policy and the bioethical implications of tobacco control. The Centers will accelerate the development of interventions to control tobacco use, speed the transfer of these approaches to communities nationwide, and train a new generation of tobacco control researchers.
Lung Cancer SPOREs. NCI currently funds seven lung cancer SPOREs. The Lung SPORE at the University of Pittsburgh Cancer Institute is studying the mechanisms for increased susceptibility to lung cancer in women.
Tobacco-Related Cancers
While lung cancer is the leading tobacco-related cancer, the following cancers in women are also associated or linked with exposure to tobacco smoke.
Endometrial Cancer. Some research suggests that female smokers have half the risk of nonsmokers for developing endometrial cancer. Though the precise mechanism is unknown, nicotine has been shown to decrease the levels of estrogen, which might decrease the growth of estrogen-sensitive tumors such as endometrial cancer and some breast cancers.
Colon Cancer. The PLCO Cancer Trial sponsored by NCI has reported an association between smoking, polyps, and colorectal cancer. Previous studies have shown that smoking increased the risk by two-fold of colon cancers that display MSI, seen in 15 percent of colon cancers. MSI increased with the amount of cigarettes smoked, the duration of smoking, and the age of smoking initiation. The time from smoking initiation to colon cancer diagnosis could be 35 years, which could explain how colon cancer rates during 1990s increased subsequent to smoking increases in the 1970s.
Cervical Cancer. Active cigarette smokers were identified as having a two-fold greater risk of developing cervical cancer. Risk appears to be dose dependent for smokers and nonsmokers exposed to environmental tobacco smoke. The findings of increased amount of tobacco-specific cancer-causing agents in the cervical lining of smokers may provide the mechanism for initiation of disease.
Biology
Molecular Characterization. The MMHCC developed a mouse model for lung adenocarcinoma, commonly found in tobacco users. The model has been instrumental in identifying a pathway for tumorigenesis. Researchers have recently reported the ability to discern patterns of gene expression for squamous cell carcinoma and adenocarcinoma, two common types of non-small cell lung cancers (NSCLC) that account for 80 percent of lung cancers.
Although nicotine is not considered a carcinogen, recently published data suggests that it plays a role in making cells resistant to apoptosis, allowing them to survive longer and undergo cancerous transformation. These findings provide evidence for treatments directed toward inhibiting survival pathway initiation and imply that nicotine replacement therapy is not without hazards, though their use to quit smoking would outweigh cost of continued tobacco use.
Risk Factors
Smoking. Some research has shown that smoking increases the risk for tobacco-related cancers more in women than in men. Current research is looking at the differences between how men and women metabolize tobacco carcinogens, express related genes, and repair DNA.
Lung cancer mortality is about 13 times higher among current female smokers than among women who have never smoked and former smokers who retain a heightened cancer risk for the remainder of their lives. Despite these facts, many women continue to smoke and many young girls start smoking. As smoking in adult women began to decline, rates in teenage girls rose sharply. In 2000, almost 30 percent of high school senior girls reported smoking a cigarette within the last 30 days, a decrease from 1999 when tobacco use peaked at 35 percent among teenage girls. Between the mid-1970s and the early 1990s, smoking rates in African American girls declined substantially while rates among white girls only experienced a small decline. Currently, African American girls are less likely to be smokers than white girls.
The 2001 Surgeon General's Report on Women and Smoking describes prevalence rates in U.S. females. Rates were highest among Native Americans and Alaskan Natives (34.5 percent); white women were next (23.5 percent), followed by African American women (21.9 percent). Hispanic and Asian/Pacific Islander women have rates of 13.8 percent and 11.2 percent, respectively. During pregnancy, women will stop smoking, either with assistance or spontaneously, but 12 months after delivering, 67 percent will have resumed smoking. By educational level, smoking prevalence is nearly three times higher among women with 9 to 11 years of education than among women with 16 or more years of education.
Environmental Tobacco Smoke. Each year, about 3,000 nonsmoking adults die of lung cancer as a result of breathing second-hand smoke. Recent epidemiologic studies of nonsmoking women exposed to tobacco smoke in the home estimate that there is about a 20 percent higher risk for lung cancer in these women than in unexposed women. 3 hours of second-hand smoke per day increases cervical cancer risk by three-fold. A study of nonsmoking women in China found an association between levels of exposure to home fuel in poorly ventilated homes and development of lung cancer.
Genetic Epidemiology of Lung Cancer and Smoking Study. NCI will support an interdisciplinary case-controlled study on how tobacco and genes influence both lung cancer and smoking by incorporating the study of siblings and an extensive biospecimen collection. Another study in Italy, exploring the genetic determinants of lung cancer and smoking, will also look at gene-environment interactions.
Cancer Survivors. An NCI study reported that people who received chemotherapy, radiotherapy, or both for the treatment of Hodgkin's Disease are at increased risk for developing lung cancer. Those who also smoke increase their risk about five-fold. Survivors of childhood cancer were less likely to smoke than the general population; however, those diagnosed during late childhood, those with lower income, and those with less education became smokers more often than their opposing counterparts. Survivors who began smoking were more likely to continue the habit if they began smoking after the age of 13, were less educated, or developed brain cancer that required radiation treatment. Analysis of these patterns is important for smoking prevention and cessation efforts in high-risk groups.
Prevention and Control
NCI, through public and private partnerships, promotes research and interventions in tobacco surveillance, prevention, and control in all populations. Some of these efforts include State and Community Tobacco Control Intervention, Youth Prevention and Cessation Research, and Monitoring Progress in Tobacco Control. Resources, such as the Tobacco Intervention Research Clinic, the Smoking Cessation Service, and the Smoking and Tobacco Control Monograph series are available to researchers and the public through the Tobacco Control Research Branch.
Current NCI activities include:
- Studies on Tobacco Use and Addiction in Women. Studies on reducing tobacco use by pregnant women are focused on helping low income women quit, testing the ability of women's partners to assist them in quitting, and preventing relapse after delivery. Another study examines the relationship between smoking and major depressive disorder, a problem that disproportionately affects women. NCI also is funding a major study of African American women's health that includes an examination of smoking behavior. Smoking Cessation During Pregnancy. A study sponsored by NCI's Tobacco Control Research Branch includes partner-assisted intervention for pregnant smokers, acceleration of progress in smoking cessation in pregnancy, and motivational enhancement therapy for pregnant smokers.
- Efficacy of Exercise as an Aid for Smoking Cessation. Researchers at the Miriam Hospital and Brown University School of Medicine studied whether sedentary female smokers in a behavioral smoking cessation program would benefit from vigorous exercise. This study demonstrates that vigorous exercise, used in conjunction with a comprehensive cognitive behavioral smoking cessation program, leads to improved rates of smoking abstinence.
- Nicotine Addiction. An NCI study demonstrated that variations in the two genes that regulate dopamine are related to the age at which a person started smoking, the likelihood of being a current smoker, and the length of periods of smoking abstinence. Scientists continue to investigate whether a specific variation in the dopamine receptor gene will make an individual less likely to smoke, or if they smoke, if it would make them less likely to become addicted. Complementary studies conducted by TTURC investigators have found regulator genes for dopamine activity that contribute to identifying which smokers will be able to quit. These genes do not appear to affect the success of cessation treatment drug bupropion to aid in cessation. Prenatal exposure to nicotine was found to increase the probability of progressing to regular use. Other NCI-supported studies in teenagers attempting to quit smoking found nicotine withdrawal symptoms as soon as 1 month after smoking initiation.
Early Detection, Diagnosis, and Prognosis
The National Lung Screening Trial was recently initiated to determine whether spiral computerized tomography (spiral CT) or chest X-ray will reduce lung cancer mortality prior to symptom onset. The 50,000 patient, 30-site study is being coordinated by NCI through two established networks, PLCO and American College of Radiology Imaging Network. Blood, sputum, and urine samples have been obtained for future biomarker research.
The American College of Surgeons Oncology Group, an NCI-sponsored network, is evaluating PET for lung cancer staging. Another program, Novel Imaging Technologies, facilitates new imaging technology through collaborative efforts between academia, industry, and foreign institutes. A group of NCI-supported investigators are working on the next-generation PET/CT scanner for greater localization and evaluation in difficult cancers.
Studies in the Director's Challenge program have developed methods in gene expression profiles to evaluate survival prognosis after surgery, in patients with early-stage NSCLC.
Cancer Control, Survivorship, and Outcomes Research
Quality of life (QOL) issues associated with lung cancer are being investigated by NCI-supported scientists through self-reporting by 5-year survivors of NSLC. The evaluation was designed to look into pulmonary function, depression and anxiety, tobacco use, social and spiritual well-being, and demographics as they affect QOL. Depression was strongly associated with lower QOL, while co-morbid conditions were weakly indicative of QOL. It was noted that non-white participants assessed at higher QOL and mental health than whites. African Americans diagnosed with advanced NSCLCs and treated with systemic chemotherapy were found to present with poor performance and greater weight loss. Findings of the studies suggest that socioeconomic status may play an important role in QOL.
