Full Text PA-96-008 EPIDEMIOLOGY OF LUNG CANCER: INTERDISCIPLINARY STUDIES NIH GUIDE, Volume 24, Number 41, December 1, 1995 PA NUMBER: PA-96-008 P.T. 34 Keywords: Cancer/Carcinogenesis Epidemiology Pulmonary Diseases National Cancer Institute National Institute of Environmental Health Sciences PURPOSE The Division of Cancer Epidemiology and Genetics of the National Cancer Institute (NCI) invites grant applications for innovative interdisciplinary studies to better understand the etiology of adenocarcinoma and small cell carcinoma of the lung and the means of prevention. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement (PA), Epidemiology of Lung Cancer: Interdisciplinary Studies, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001000473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, research laboratories, units of State and local governments, eligible agencies of the Federal government, and small businesses. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT Support of this program will be through individual research project grants (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. RESEARCH OBJECTIVES Background Lung cancer is now a leading cause of cancer death in industrialized countries and is rising in many developing countries. Thun et al. (1), who examined changes in smoking-specific death rates from the 1960s to the 1980s in the U.S. reported that lung cancer surpassed coronary heart disease as the largest single contributor to smoking-attributable death among White middle-class smokers. In 1930, the age-adjusted lung cancer death rate among U.S. males was about 5/100,000 per year; it rose to 55.9 in 1970 and to 74.9 in 1987. Among females in the U.S., the corresponding lung cancer death rates were 3.0, 12.2 and 28.5, respectively (2). In 1994, lung cancer accounted for an estimated 172,000 incident cases (100,000 males and 72,000 females) and 153,000 deaths (94,000 males and 59,000 females) (3). Cigarette smoking is the leading cause of lung cancer. While smoking cessation programs are critical to reduce the burden of lung cancer in our society, additional research is also warranted to clarify the reasons for changes in the distribution of the major histologic types during the last 40 years and gender and racial differences in risk. Our lack of understanding of the reasons for these patterns reflects the inadequacy of our knowledge of lung carcinogenesis at the histology-specific level. This level of understanding will also impact clearly on our ability to prevent the disease. Several investigators have reported on time trends. Vincent (4) found adenocarcinoma and squamous cell carcinoma to be the more common histologic types among lung cancer patients presenting to the thoracic surgery department of Roswell Park Memorial Institute between 1962 and 1975. Adenocarcinoma increased progressively from 17.6 percent of the total cases in 1962 to 29.8 percent by 1975, while squamous cell carcinoma represented 48.6 percent of the total cases in 1962 but decreased to 25.5 percent in 1975. Devesa et al. (5), reporting on changing patterns of lung cancer by histologic type for the period 1969-1986 for five geographic areas (Atlanta, Connecticut, Detroit, Iowa and San Francisco- Oakland) covering seven percent of the U.S. population, indicated that for all sex-race groups combined, age-adjusted incidence of lung cancer increased three percent per year from 38.6/100,000 person-years during 1969-71 to 58.4/100,000 person-years during 1984-86. The rate rose 25 percent among white men, about 50 percent among black men, and over 150 percent among both black and white women. Squamous cell carcinoma rates increased 50 percent or less among men and more than doubled among women. Adenocarcinoma and small cell carcinoma rates doubled among men and more than tripled among women. As a result, the histologic distribution of lung cancer changed over time. Squamous cell carcinoma remains the most common type among men. Among women, however, adenocarcinoma is the most frequent type; the rates of small cell carcinoma exceeds slightly those of squamous cell carcinoma among white women only. Recently, Travis et al (6) reported analyses of Surveillance, Epidemiology, and End Results (SEER) Program data on lung cancer for the period 1973-1987. The percentage of lung cancers that were adenocarcinoma in all race-sex groups combined increased to 32 percent, surpassing squamous cell carcinoma as the most frequently occurring histologic type. Squamous cell carcinoma, however, continues to constitute a large proportion (29 percent) of lung tumors. The race, gender and time patterns of adenocarcinoma and small cell carcinoma cannot be readily explained. It has been suggested that advances in techniques for establishing the diagnosis of lung cancer should be considered in interpreting temporal trends of incidence by histologic type. Changing patterns of classification by pathologists may also have influenced the reported increase in frequency of adenocarcinoma. Cigarette smoking is a stronger risk factor for squamous cell carcinoma and small cell carcinoma than for adenocarcinoma of the lung (5). Smoking intensity, duration, types of cigarette smoked, cessation, or different degree of susceptibility to carcinogens present in tobacco smoke may differentially affect the development of the various histologic types of lung tumors. Newer cigarettes containing lower amounts of tar, as determined by the Federal Trade Commission method, may be more harmful than older brands. Women may be at a higher elevated risk of lung cancer than men due to greater exposure to newer brands and/or to gender-related susceptibility (7,8). The greater lung cancer risk in blacks compared to that in whites may be due to racial differences in carcinogen metabolism or for reasons similar to those responsible for gender differences. Occupational determinants of lung adenocarcinoma have not been well investigated. Few studies have examined the differences in occupational risks for histologic types of lung cancer, but associations between occupations and specific histologic types have been suggested. Adenocarcinoma of the lung was elevated among carpenters, and cabinet and furniture makers (9). Occupational exposure to bischloromethyl ether (10) and radon (11) preferentially influence small cell carcinoma. With regard to diet, positive associations have been seen with lipid consumption, fat and cholesterol, and inverse associations with various carotenoids, vitamin C, and retinol, and with fruits and vegetables as a group (12). Immunologic and hormonal factors have been suggested to affect risk of adenocarcinoma (13,14), and familial patterns have been observed (15). Findings from a multicenter case-control study of lung cancer in nonsmoking women indicated an overall 30 percent increased risk associated with exposure to environmental tobacco smoke from a spouse, with a 50 percent elevated risk of lung adenocarcinoma (16). Other adult life exposures in household, occupational and social settings were each associated with a 40 to 60 percent increased risk of lung adenocarcinoma (16). Approximately half of all lung cancers among current nonsmokers could be attributed to a history of smoking, dietary intake of saturated fat, nonmalignant lung disease, environmental tobacco smoke, occupational exposures including asbestos, a family history of lung cancer and domestic radon (17). Thus half of the lung cancer incidence among nonsmokers remains unexplained. Research Scope and Goals The reasons for the increases in adenocarcinoma and small cell carcinoma of the lung in the U.S. remain to be fully explained. Changing diagnostic trends should be considered as one possible reason, and examined through standardized review of a sample series of cases that are representative of those occurring since the 1950s. There is a paucity of understanding of the environmental and host factors and the mechanisms of induction for specific types of lung cancer. In particular, further research is needed to elucidate the etiologic factors that influence the upwards time trends in lung adenocarcinoma and small cell carcinoma. The areas of research listed below are not intended to be all- inclusive, but are designed to give the applicant some direction for the types of research that the NCI is interested in stimulating to enhance knowledge about the etiology of lung adenocarcinoma and small cell carcinoma and means for their prevention. 1. Epidemiologic studies of lung adenocarcinoma and/or small cell carcinoma in smokers, with detailed collection of tobacco use data, assessment of risk modifiers, and evaluation of susceptibility factors; pooled analysis of existing data sets for lung adenocarcinoma and small cell carcinoma; studies of non- tobacco environmental/occupational exposures and lung adenocarcinoma and small cell carcinoma risk. 2. Studies of host susceptibility factors in relation to lung cancer type, such as P450 expression/polymorphisms, glutathione S-transferase enzymes, hormonal factors, and diet. 3. Studies of the molecular mechanisms of lung adenocarcinoma and/or small cell carcinoma in laboratory animals and humans to assess the role of novel oncogenes or tumor suppressor genes; investigation of carcinogen metabolic activation and detoxification in human pulmonary cells; development of biomarkers of chemicals in tobacco products, in the general environment or in occupational settings that induce lung adenocarcinoma, and small cell carcinoma, including DNA adducts. Consideration should also be given to DNA adduct repair in human pulmonary cells. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH- sponsored biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women and Study Populations, and Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research," which was reprinted in the Federal Register on March 28, 1994 (59 FR 14508-14513) to correct typesetting errors in the earlier publication, and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies from these sources or from the program staff or contact person listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) and will be accepted at the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301-710-0267. The completed original application and five legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD, 20817 (for courier/overnight service) REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The Initial review group will also examine the provisions for the protection of human subjects and animal welfare and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to the NCI. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review, availability of funds, and program priority. INQUIRIES Inquiries are encouraged, particularly during the planning phase of the grant applications. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. A.R. Patel Division of Cancer Epidemiology and Genetics National Cancer Institute 6130 Executive Boulevard, Suite 535, MSC 7395 Bethesda, MD 20892-7395 Telephone: (301) 496-9600 FAX: (301) 402-4279 Email: Jasonc@EPNDCE.NCI.NIH.GOV Dr. Gwen W. Collman Chemical Exposures and Molecular Biology Branch National Institute of Environmental Health Sciences P.O, Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-4980 FAX: (919) 541-2843 Email: collman@niehs.nih.gov Direct inquiries regarding fiscal matters to: Mr. E. C. Melvin Grants Administration Branch National Cancer Institute Executive Plaza South 6120 Executive Boulevard, Suite 243, MSC 7150 Bethesda, MD 20892-7150 Telephone: (301) 496-7800, EXT 258 FAX: (301) 496-860 David L. Mineo Grants Management Branch National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-7628 FAX: (919) 541-2860 Email: MELVINE@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.393. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-140, as amended by Public Law 99.158, 42 USC 241 and 285) and administered under HHS policies and grant regulations. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health System Agency review. The Public Health Service (PHS) strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, The Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American People. References: 1.Thun, M.J., Day-Lally, C.A., Calle, E.E., et al. Excess mortality among cigarette smokers: changes in a 20-year interval. Am. J Public Health, 85: 1223-1230, 1995. 2. Wynder, E.L. and Hoffmann, D. Smoking and lung cancer: scientific challenges and opportunities. Cancer Res., 54: 5284- 5295, 1994. 3. Boring, C.C., Squires, T.S., Tong, T., et al. Cancer statistics, 1994. Ca. Cancer J. Clin., 44: 7-26, 1994. 4. Vincent, R. G., Pickren, J.W., Lane, W.W. et al. The changing histopathology of lung cancer: a review of 1682 cases. Cancer, 39: 1647-1655, 1977. 5. Devesa, S. S., Shaw, G.L., and Blot, W.J. Changing patterns of lung cancer by histologic type. Cancer Epidemiol., Biomarkers Prev., 1: 29-34, 1991. 6. Travis, W.D., Travis, L.B., and Devesa, S.S. Lung cancer. Cancer, 75: 191-202, 1995. 7. Risch, H.A., Howe, G.R., Jain, M., et al. Are female smokers at higher risk of lung cancer than male smokers? A case-control analysis by histologic type. Am. J. Epidemiol., 138: 281-293, 1993. 8. Harris, R.E., Zang, E.A., Anderson, J.I., et al. Race and sex differences in lung cancer risk associated with cigarette smoking. Int. J. Epidemiol., 22: 592-599, 1993. 9. Zahm, S.H., Brownson, R.C., Chang, J.C., et al. Study of lung cancer histologic types, occupation and smoking in Missouri. Am. J. Ind. Med., 15: 565-578, 1989. 10. Pasternack, B.S., Shore, R.E., and Albert, R.E. Occupational exposure to chloromethyl ethers. J. Occup. Med., 19: 741-746, 1977. 11. Samet, J.M. Radon and lung cancer. J. Natl. Cancer Inst., 81: 745-757, 1989. 12. Patel, A.R. and Obrams, G.I. Meeting Report: Adenocarcinoma of the lung. Cancer Epidemiol., Biomarkers Prev., 4: 175-180, 1995. 13. Fraumeni, J.F. Jr., Wertelecki, W., Blattner, W.A., et al. Varied manifestations of a familial lymphoproliferative disorder. Am. J. Med., 59: 145-151, 1975. 14. Gao, Y.T., Blot, W.J., Zheng, W., et al. Lung cancer among Chinese women. Int. J. Cancer, 40: 604-609, 1987. 15. Mulvihill, J.J. Host factors in human lung tumors: an example of ecogenetics in oncology. J. Natl. Cancer Inst., 57: 3-7, 1976. 16. Fontham, E. T. H., Correa, P., Wu-Williams, A., et al. Lung cancer in nonsmoking women: a multicenter case-control study. Cancer Epidemiol., Biomarkers Prev., 1: 35-43, 1991. 17. Alavanja, M.C.R., Brownson, R.C., Benichou, J., et al. Attributable risk of lung cancer in lifetime nonsmokers and long-term exsmokers. Cancer Causes and Control, 6: 209-216, 1995. .
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||