Full Text CA-94-018 PROGRAM PROJECTS IN NUTRITION AND BASIC BIOLOGY RESEARCH FOR CANCER PREVENTION NIH GUIDE, Volume 23, Number 22, June 10, 1994 RFA: CA-94-018 P.T. 34 Keywords: Cancer/Carcinogenesis Nutrition/Dietetics Disease Prevention+ National Cancer Institute Letter of Intent Receipt Date: July 25, 1994 Application Receipt Date: November 18, 1994 PURPOSE The Division of Cancer Prevention and Control and the Division of Cancer Etiology, National Cancer Institute (NCI), invite Program Project Grants for multidisciplinary nutrition and basic biology research relevant to the prevention of cancer. Specifically, they seek to encourage application of the techniques of molecular biology and molecular genetics to address questions about the fundamental role of nutrition in the initiation, promotion, progression, and prevention of cancer and the use of that knowledge to develop dietary interventions for the prevention of cancer, with a special emphasis on breast cancer, prostate cancer, and cancer in women and minorities. This Request for Applications (RFA) focuses on understanding the roles of dietary patterns, individual dietary constituents, food preparation techniques, and nutritional status in the development and prevention of cancer. The objectives of this RFA for Program Project Grants are to increase the pool of quality applications addressing nutrition and human cancer prevention using multidisciplinary approaches; to stimulate the use of modern biological approaches and techniques to elucidate the effects of nutrition on cancer initiation, promotion, progression, and prevention; and to promote the translation of knowledge of the impact of nutrition on the basic biology of cancer into dietary interventions for its prevention. Application of the tools and techniques of the basic biological sciences in research designed to increase understanding of the complex role of nutrition in cancer prevention will be enhanced significantly by a mechanism that promotes collaborations across disciplines and across institutions. Therefore, investigators are encouraged to submit Program Project Grant (P01) applications for a multidisciplinary research program with a focused theme and a minimum of three interrelated and synergistic individual component projects that comprise basic research efforts and at least one component project involving human subjects or human tissues. 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 RFA, Program Projects in Nutrition and Basic Biology Research for Cancer Prevention, is related to the priority areas of cancer and nutrition. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Domestic non-profit and for-profit organizations and institutions, public and private, are eligible to apply. Applications may be submitted from a single institution or may include arrangements with multiple institutions if appropriate. Applications from or involving minority institutions and from minority and women investigators are encouraged. Foreign institutions are not eligible. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) Program Project Grant (P01). Applicants will be responsible for the planning, direction, and execution of the proposed projects. The total project period for an application submitted in response to this RFA must not exceed four years. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the amount of the direct cost awards will vary from $700,000 to $1,000,000. This is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE Up to $4 million in total costs per year for up to four years will be committed specifically to fund applications that are submitted in response to this RFA. It is anticipated that three to four awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES A. Background Associations of dietary patterns and constituents with mortality and incidence have been suggested for a variety of cancers, including breast, prostate, lung, colon, stomach, esophagus, and cervix. Among these, breast and prostate cancer are of particular significance because of the large numbers of persons affected in the United States. The state of current knowledge of the role of nutrition, in terms of the effects of dietary patterns, types and levels of individual dietary constituents, and nutritional status, on the development and prevention of breast, prostate, and other cancers is still rudimentary. It has been subject to the inherent methodological limitations and inadequacies of the epidemiologic studies and animal models upon which it is largely based. Nonetheless, the available evidence has been sufficient to permit the provision of general dietary guidance that may help reduce risk of cancer and to justify the conduct of clinical trials to test the efficacy of dietary modification or supplementation with nutrients in the primary and secondary prevention of various cancers. Further significant advances in understanding the role of nutrition in cancer prevention require answers to questions about the fundamental mechanism(s) of action of dietary patterns and dietary constituents in the initiation, promotion, progression, and prevention of cancer, in the context of nutrient-gene-environmental interactions. Information is needed regarding nutrient and dietary non-nutrient microconstituent interactions with and effects on cellular metabolism, genomic stability, intracellular signal transduction, the net expression of growth-promoting and growth-inhibiting genes, and other modulators of gene expression and carcinogenesis. More information is also needed about the transport of nutrients to target tissues and about individual variability in susceptibility and response to nutrient effects. Such knowledge of the basic mechanisms of action of dietary components in cancer development is needed to provide informed recommendations about the optimal range of intake of specific dietary constituents and to refine and individualize dietary guidance for prevention of cancer. Studies that provide the necessary information fall within the province of bionutrition and encompass research on nutrients at the cellular level and the metabolic and behavioral consequences of food or nutrients in living organisms including humans. With the increasing recognition of the invaluable contributions of the techniques of molecular biology and molecular genetics to all facets of biomedical research, it is appropriate that their use in addressing important questions about nutrition and cancer prevention be encouraged. The potential for these new technologies to revolutionize many aspects of the science of nutrition, by increasing understanding of the nutrient-cell interactions that affect transition from healthy to diseased cells and permitting more reliable determination of the nutrient requirements for optimal health and functional capacity, was given explicit recognition in the trans-NIH Bionutrition Initiative. Although bionutrition rests firmly on the foundation of the modern biological sciences, it has been conceptualized as encompassing a broad range of activities from basic research through translational research to practical applications. Accordingly, this RFA encourages the submission of multidisciplinary research project applications in the form of Program Project Grants (P01). This type of award is intended to support a broadly based multidisciplinary program that has a well-defined central research focus or objective and may include support for common supporting resources (cores) required for the conduct of the component research projects. The central research focus of a Program Project Grant involves several disciplines or several aspects of one discipline and may involve multiple institutions. The individual projects must be interrelated and synergistic; hence, they result in a greater contribution to program goals than if each project were pursued separately. Individual investigators may apply their specialized research capabilities to basic research projects, clinical research projects, cancer prevention and control research projects, or combinations of such projects as they relate to the focused central theme of the overall Program Project. Applications are encouraged especially from investigative teams with members trained in molecular, biological and genetic techniques and nutritional science who have an interest in applying those techniques and knowledge to address questions regarding nutrition and cancer prevention. Program Projects responsive to this RFA must comprise basic research efforts and at least one component project involving studies of human subjects or human tissues. Applicants are encouraged to structure Program Projects that are no larger than necessary to achieve an effective collaborative effort among the participating basic biology and nutrition investigators. B. Research Areas of Interest The studies encouraged by this RFA will employ innovative approaches to examine fundamental effects of nutrients and other food constituents on initiation, promotion, progression, and prevention of cancer, as well as individual variability in response, to develop more effective nutrition interventions for prevention of cancer, especially breast and prostate cancer and other cancers affecting women and minorities. A wide variety of potential Program Projects, comprising individual projects ranging from basic to translational research and practical applications, may be considered for support; however, all applications must delineate clearly the relevance of each proposed individual research project, especially those with a basic biology focus, for the prevention of human cancer. Illustrative, but not exhaustive, examples of research areas relevant to nutrition and basic biology research for the prevention of cancer are as follows: o Evaluate nutrient-genome interactions in carcinogenesis and anticarcinogenesis, e.g., nutrient effects on DNA repair or modulation of gene expression. o Examine the potential for nutrients or other dietary constituents to influence the activation of oncogenes or inactivation of tumor suppressor genes. o Study nutrient influences on differentiation and on signals induced by physiological or chemical differentiation in various tissues. o Evaluate nutrient effects on growth factors for cellular transformation, including the ability to block or prevent the interaction of growth factors with receptors. o Examine nutrient-carcinogen-promoter interactions, including cellular defense mechanisms against environmental carcinogens/promoters that may be regulated by dietary factors. o Elucidate mechanisms and controls of nutrient transport to target sites in various tissues. o Quantify dose-response relationships for nutrients, nutrient derivatives, and other bioactive dietary constituents as part of the evaluation of their absorption, metabolism, and distribution in target tissues and their effects on molecular and cellular events. o Identify biomarkers indicative of early cellular transformation that may be monitored in nutrition epidemiologic studies and modulated in dietary intervention trials. o Identify biomarkers that will provide improved assessment of dietary intake and/or nutritional status for use in nutrition epidemiologic studies and dietary intervention trials. o Characterize the nature, extent, and causes of individual variability in cancer risk and in responses to dietary constituents. o Develop dietary intervention strategies to modulate expression of genetically determined cancer risk, including risk resulting from loss of response to natural regulators of proliferation and/or risk resulting from blocked expression of differentiation (maturation) programs. o Conduct small-scale clinical/metabolic intervention studies to test dietary modifications with potential for cancer prevention developed on the basis of knowledge of nutrient-genomic interactions. SPECIAL REQUIREMENTS The Program Project Grant is intended solely for the support of a multidisciplinary or multifaceted research program that has a focused theme. This unique grant mechanism builds on the leadership of the principal investigator and the interaction of the participating investigators to integrate the individual projects in a way that accelerates the acquisition of knowledge beyond that expected from the same projects conducted separately, without combined leadership or a common theme. A project within a Program Project is similar to the traditional research grant application in the sense that each is reviewed for scientific merit. However, a component project additionally is evaluated within the context of the special collaborative interrelationships required for a Program Project. In order to be responsive to this RFA, a Program Project must include basic research efforts and at least one component project involving studies of human subjects or human tissues. The relevance of each component project, especially those projects with a basic biology focus, to the prevention of human cancer must be clearly delineated. A Program Project Grant may contain one or more core component(s), each with a separate budget, for administrative or research support services that are required for and shared solely within this particular Program Project. Each core must provide essential facilities or services for two or more projects judged to have substantial merit. There is no allowance for unspecified developmental research funds (seed money) in Program Project Grants. A Program Project should include a sufficient number of scientifically meritorious projects to promote an effective collaborative effort among the participating investigators. For this RFA, Program Projects should be no larger than necessary to achieve the desired collaboration among basic biology and nutrition investigators. To be eligible for an award, a Program Project must consist of a minimum of three scientifically meritorious projects. There is no limit for the maximum number of projects to be included in a Program Project; however, the Program Project should not be so large that it exceeds the scientific and administrative leadership capability of the principal investigator, or that it loses a tight focus. In the peer review process, components not recommended for further consideration are considered in the peer review evaluation of the principal investigator's scientific judgment and program administration skills. The principal investigator of the Program Project Grant must be an established scientist with a strong record of accomplishment, who is substantially committed to and capable of exercising the responsibility for the scientific leadership, integration and administration of the entire Program Project. Also, the component projects should be directed by investigators who are experienced in the conduct of independent research and whose backgrounds and interests relate sufficiently to one another to allow for integrated group pursuit of the proposed Program Project goals and objectives. STUDY POPULATIONS 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-supported 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 in 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 of 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 persons listed below. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by July 25, 1994 a letter of intent that includes the names of the principal investigator and principal collaborators; a descriptive title of the potential application and a list of titles for the anticipated components of the P01; identification of the organization(s) involved; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, it is requested in order to provide an indication of the number and scope of applications to be reviewed and to allow NCI staff to avoid conflict of interest. The letter of intent is to be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 Bethesda, MD 20892 Telephone: (301) 496-3428 FAX: (301) 402-0275 APPLICATION PROCEDURES The regular research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892; and from the NCI program administrators named under INQUIRIES. General instructions for the preparation of the Program Project Grant application are contained in the application form PHS 398 (rev. 9/91). Instructions provided in the PHS 398 application kit are designed primarily for traditional research project (R01) applications. Program Project applications require additional information and a special format as described in the publication, "Program Project Grant of the National Cancer Institute: Guidelines 1993." Applicants may request a copy of this publication from the NCI Referral Officer listed under LETTER OF INTENT. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the title of the RFA, "Program Projects in Nutrition and Basic Biology Research for Cancer Prevention," and the RFA number, CA-94-018, must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact, clear, and single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At time of submission, two additional complete copies of the application must be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Rockville, MD 20852 (if using overnight mail services) Bethesda, MD 20892 (if using U.S. mail) Applications must be received by November 18, 1994. If an application is received after that date, it will be returned to the applicant without review. Also, the DRG will not accept any application in response to this RFA that is the same as a P01 application currently being considered by any other NIH review group or awarding unit. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator should be included with the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and responsiveness by the NCI. Incomplete applications will be returned to the applicant without further consideration. If NCI staff find that the application is not responsive to the RFA, it will be returned without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI in accordance with the review criteria stated below. As part of the initial merit review, a process (triage) may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and be assigned a priority score. Applications determined to be non-competitive will be withdrawn from further consideration and the principal investigator/program director and the official signing for the applicant organization will be promptly notified. The second level of review by the National Cancer Advisory Board considers the special needs of the NCI and the priorities of the National Cancer Program. Peer review for scientific and technical merit of each Program Project application submitted in response to this RFA will emphasize two major aspects: (1) review of the program as an integrated research effort focused on a central theme and (2) review of the merit of individual research projects and core components. Review criteria for the program as an integrated effort include: o Scientific merit of the overall program. o Significance and importance of the Program Project objectives. o Coordination, interrelationships and synergism among the meritorious research projects and core components as related to the common theme of the Program Project. o Advantages of conducting the proposed research as a Program Project rather than through separate research efforts. o Qualifications of the principal investigator to serve as both the scientific and administrative leader of the entire Program Project. o Adequacy of the commitment (percent effort) of the principal investigator to the Program Project. o Ability of the principal investigator to select individual projects for both scientific excellence and relatedness to the theme of the Program Project and actively promote interactions and collaborations. o Presence of an organizational and administrative structure appropriate for effective attainment of the Program Project objectives. o Mechanisms for internal quality control of the research. o Mechanisms for regular communication and coordination among investigators. o Institutional environment in which the research is conducted, including the availability of space, equipment, and patients or subjects, as well as the physical proximity of program participants. o Appropriateness of the size of the Program Project. Review criteria for individual projects include: o Scientific merit of the individual project in the context of the proposed program, considering the following factors: --Specific scientific objectives of the project that benefit significantly from, depend upon, or contribute to collaborative interactions with other projects in the program. --Qualifications, experience and commitment (percent effort) of the project leader and investigators responsible for the individual research project. --Adequacy of the proposed means for protecting against or minimizing potential adverse effects upon humans, animals, or the environment. --Adequacy of adherence to guidelines for including gender and minority representation in any study population. --Appropriateness of the budget. o Intrinsic scientific merit of the proposed project. Review criteria for core(s) include: o Utility of the core to the Program Project. o Quality of the facilities or services provided by this core (including procedures, techniques, and criteria for prioritization). o Qualifications, experience, and commitment of the personnel involved in this core. o Appropriateness of the budget and accountability for distribution of costs to projects. AWARD CRITERIA The anticipated date of award is July 1, 1995. Scientific merit, as reflected by the priority score; availability of funds; and programmatic priorities will be considered in making awards pursuant to this RFA. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Susan M. Pilch, Ph.D. Division of Cancer Prevention and Control National Cancer Institute Executive Plaza North, Suite 212 Bethesda, MD 20892 Telephone: (301) 496-8573 FAX: (301) 402-0553 Carl E. Smith, Ph.D. Division of Cancer Etiology National Cancer Institute Executive Plaza North, Suite 700 Bethesda, MD 20892 Telephone: (301) 496-5471 FAX: (301) 496-1040 Direct inquiries regarding fiscal matters to: Robert E. Hawkins Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800 Ext. 213 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.399, Cancer Control. Awards will be made under the authority of the Public Health Services Act, Title IV, Section 301 (Public Law 78-410, 42 USC 241 and Section 412, as amended by Public Law 99-518, 42 USC 285a-1) and administered under Federal regulations 42 CFR Part 52 and PHS grant policies 45 CFR Part 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12732 or Health Systems Agency review. The Public Health Service strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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