Full Text CA-95-010 HUMAN METABOLIC STUDIES OF MODIFICATION OF DIETARY FATTY ACID INTAKE FOR PREVENTION OF BREAST, PROSTATE, AND COLON CANCER NIH GUIDE, Volume 24, Number 14, April 14, 1995 RFA: CA-95-010 P.T. 34 Keywords: Cancer/Carcinogenesis 0715036 Nutrition/Dietetics Disease Prevention+ National Cancer Institute Letter of Intent Receipt Date: May 26, 1995 Application Receipt Date: July 12, 1995 PURPOSE The Division of Cancer Prevention and Control, National Cancer Institute (NCI) seeks to stimulate investigator-initiated research to elucidate mechanisms by which modification in amount and/or type of dietary fat/fatty acids consumed may reduce risk for human breast, prostate, and/or colon cancers. The goal is to clarify understanding of the relationship between dietary fatty acids and cancer in order to refine dietary guidance on the optimal amount and type of dietary fat to reduce the risk of several of the most common cancers in the United States. 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 Request for Applications (RFA), Human Metabolic Studies of Modification of Dietary Fatty Acid Intake for Prevention of Breast, Prostate, and Colon Cancer, is related to the priority areas of nutrition and cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this RFA may not exceed four years. The anticipated award date is April 1996. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. This RFA 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 $1.5 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 six to eight 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 Background In the United States, breast cancer is the most common malignancy among women; the current lifetime risk of an American woman developing breast cancer is approximately 11 percent. Only lung cancer exceeds breast cancer as a cause of cancer death in U.S. women. Adenocarcinoma of the prostate is the most common form of cancer in adult males, excluding nonmelanoma skin cancer. Prostate carcinoma now surpasses the incidence of lung cancer and represents the second most common cause of male cancer death. Cancer of the colon and rectum is the third most common cause of cancer deaths in both women and men. The etiologic factors responsible for the development of these three cancers are not fully understood, but the level and type of dietary fat consumed have been hypothesized to contribute to the development of each. Epidemiological investigations have yielded inconsistent findings on possible associations. Most ecological studies provide evidence of a positive association between intake of both saturated and polyunsaturated, fat and breast cancer in both pre- and postmenopausal women. Case-control studies suggest a weaker positive association (primarily with saturated fat in postmenopausal women) and cohort studies suggest either a weak positive association or no association. Descriptive epidemiologic studies suggest a positive association of fat intake, particularly saturated and polyunsaturated fat, with risk of prostate cancer. Results from case-control and cohort studies are less consistent, but a number of these studies suggest a positive association with saturated or animal fat intake. For colorectal cancer, the ecological studies also support a positive association between fat intake and risk, but suggest that effects may differ by age and cancer site. There is little evidence of a consistent association with total fat intake in case-control and cohort studies, but greater evidence for a positive association with saturated or animal fat. A large body of data from experiments in laboratory rodent models of mammary and colon carcinogenesis also suggests a role for dietary fat. Chemically induced mammary cancers develop earlier and in greater incidence and number in rats fed high-fat (40 percent of calories) diets containing primarily omega-6 polyunsaturated fatty acids (PUFA) than in rats fed low-fat (10 percent of calories) diets. Less highly unsaturated fats and saturated fats have less effect than corn oil, and oils composed primarily of omega-3 PUFA have not been shown to increase mammary carcinogenesis. Results with colon cancer models have not been as consistent as those with mammary cancer models. Possible reasons for the inconsistencies in the findings between and among the epidemiological and animal studies are numerous and include errors in measuring dietary intake, biased recollection of diet history, homogeneity of dietary fat intake in case-control and cohort studies, lack of specificity or inappropriate classification of fats, inability to separate the effect of dietary fat from that of calories, poor measures of net energy balance in epidemiological studies, and failure to address the interactive effects of dietary and nondietary factors. Nonetheless, the available evidence has been judged strong enough by a number of expert groups to justify recommendations for reductions in dietary fat intake to help reduce cancer risk; the effects of dietary modification to reduce total fat intake on cancer incidence and mortality are under investigation in ongoing randomized clinical trials. In contrast to the large number of epidemiological and animal studies of dietary fat intake and risk of breast, prostate, and colon cancer, there has been less research on potential mechanisms by which modification of dietary fat intake may affect cancer risk. Additional focused mechanistic investigation should help to clarify the potential role of modification of the amount and the type of dietary fat consumed, together with the impact of a variety of interrelated factors, on the prevention of human breast, prostate, and colon cancer. Specific Objectives Applications for investigator-initiated research project grants (R01) that examine mechanisms by which dietary modification of fatty acid intake may reduce risk of human breast, prostate, and/or colon cancer are encouraged. Research topics responsive to this RFA include human metabolic studies to clarify the effects of reductions in the amount or modifications in the type of dietary fatty acids consumed on metabolic/physiologic parameters relevant to the prevention of breast, prostate, and/or colon cancer. Illustrative, but not exhaustive, examples of parameters that might be examined include: alterations in production and circulating levels of sex steroid hormones, metabolic activity and products of intestinal microflora, quantity and composition of adipose tissue, membrane permeability, prostaglandin synthesis, immune function, DNA damage and repair, and metabolism of chemical carcinogens. Dietary modifications to be evaluated may include various eating patterns that lead to a reduction in total fat intake, changes in the amounts or proportions of specific fatty acids (e.g., saturated fatty acids, trans fatty acids, omega-3 fatty acids), or inclusion of fat substitutes or novel fats in the diet. In addition, the modulating effects of interacting factors, such as caloric intake, other dietary constituents, body mass index, and genetic polymorphisms affecting susceptibility to cancer, may also be considered. 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 provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by May 26, 1995, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, 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 a subsequent application, the information that it contains allows NCI staff to estimate the potential review workload and avoid conflict of interest in the review. 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 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, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/710-0267; and from the program administrator listed under INQUIRIES. The RFA label available in the PHS 398 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 RFA title and number 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 photocopies, in one package, 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) At the time of submission, two additional 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 Bethesda, MD 20892 Rockville, MD 20852 (for courier/overnight services) Applications must be received by July 12, 1995. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. 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 the application is not responsive to the RFA, it will be returned to the applicant, who may submit it for review in competition with unsolicited applications at the next review cycle. 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, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit 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 the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; and 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 the safety of the research environment, as well as conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. AWARD CRITERIA Scientific merit, as reflected by the priority score; availability of funds; and programmatic priorities will be considered in making awards pursuant to this RFA. The anticipated date of award is April 1996. INQUIRIES 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, Room 212 Bethesda, MD 20892 Telephone: (301) 496-8573 FAX: (301) 402-0553 Email: PilchS@dcpcepn.nci.nih.gov Direct inquiries regarding fiscal matters to: Victoria R. Price Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone (301) 496-7800 Ext. 252 FAX (301) 496-8601 Email: PriceV@gab.nci.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.399, Cancer Control. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract 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 routing 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. .
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