Full Text CA-96-005
NIH GUIDE, Volume 25, Number 6, March 1, 1996
RFA:  CA-96-005
P.T. 34

  Disease Prevention+ 

National Cancer Institute
Letter of Intent Receipt Date:  April 12, 1996
Application Receipt Date:  July 19, 1996
The Division of Cancer Prevention and Control and the Division of
Cancer Biology, National Cancer Institute (NCI), are reissuing an
invitation for Program Project Grant applications for
multidisciplinary nutrition and basic biology research relevant to
the prevention of cancer, with a special emphasis on breast cancer,
prostate cancer, and cancer in women and minorities.  This Request
for Applications (RFA) seeks to improve understanding of the roles of
dietary patterns, individual dietary constituents, and nutritional
status in the development and prevention of cancer.  The objectives
of this RFA 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 in order 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 in nutrition and basic biology for
cancer prevention 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.
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), 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 Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800).
Applications may be submitted by domestic non-profit and for-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories, and units of State and local governments.
Applications may be submitted from a single institution or may
include arrangements with several institutions, if appropriate.
Foreign institutions are ineligible to apply.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.
This RFA will use the National Institutes of Health (NIH) Program
Project Grant (P01).  P01 grant applications must comply with
Guidelines for Program Project Grant of the National Cancer
Institute, as revised in 1995.  Applicants will be responsible for
the planning, direction and execution of the proposed projects.  The
total project period for applications 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 total amount of the
direct cost awards will vary.  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.
Up to $2 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 two to three 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.
A.  Background
Associations of dietary patterns, dietary constituents, or
nutritional status 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 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.
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 would 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.  These new technologies have the potential 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 by permitting more
reliable determination of the nutrient requirements for optimal
health and functional capacity.  To realize this potential,
nutritional science must encompass a broad range of activities from
basic research through translational research to practical
B.  Research Areas of Interest
The studies encouraged by this RFA should 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, in order 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 tests of 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
that may be included in proposed Program Projects are studies to:
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
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)
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.
The Program Project Grant is intended solely for the support of a
multidisciplinary or multifaceted research program that has a focused
theme.  This 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, it 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 and/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.
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 on the Inclusion of Women and Minorities as
Subjects in Clinical Research," which were published in the Federal
Register of March 28, 1994 (FR 59 14508-14513), and reprinted in the
NIH Guide for Grants and Contracts of March 18, 1994, Volume 23,
Number 11.
Investigators also may obtain copies of the policy from these sources
or from the program staff listed under INQUIRIES.  Program staff may
also provide additional relevant information concerning the policy.
Prospective applicants are asked to submit, by April 12, 1996 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:
Susan M. Pilch, Ph.D.
Division of Cancer Prevention and Control
National Cancer Institute
6130 Executive Boulevard, Room 212 MSC 7328
Bethesda, MD  20892-7328
Telephone:  (301) 496-8573
FAX:  (301) 402-0553
Email:  PilchS@dcpcepn.nci.nih.gov
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  Applications kits are available at
most institutional offices of sponsored research and may be obtained
from the Grants Information Office, Office of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714,
email:  girg@drgpo.drg.nih.gov; and from the NCI program staff listed
Instructions provided in the PHS 398 (rev. 5/95) 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
1995."  Applicants should request a copy of this publication from the
NCI Referral Officer cited below in this section.
If collaborations or subcontracts are involved that require transfer
of funds from the grantee to other institutions, it is necessary to
establish formal subcontract agreements with each collaborating
institution.  A letter of intent from each collaborating institution
should be submitted with the application.
The RFA label available in the PHS 398 (rev. 5/95) 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 2 of the face page of the application form and the YES box must
be marked.  All requirements with regard to type size, page
limitations, appendix material, etc., must be followed or
applications will be returned without review.
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
Rockledge 2, Room 1040
BETHESDA MD  20892-7710 (if using U.S. Postal Service)
Bethesda, MD  20817 (for express/courier service)
At the time of submission two additional copies of the application
must be sent to:
Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
Executive Plaza North, Suite 636
BETHESDA MD  20892-7405 (if using U.S. Postal Service)
Rockville, MD  20852 (for express/courier service)
Applications must be received by July 19, 1996.  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.  In such a case, a letter of agreement from
either the GCRC program director or principal investigator should be
included with the application.
Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness, including responsiveness to the special
application procedures, 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 in accordance with 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
National Cancer Advisory Board.
Peer review of the overall scientific and technical merit of each
Program Project application submitted in response to this RFA will
emphasize a synthesis of 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 in the context of the proposed program.
Detailed review criteria for the overall program, the program as an
integrated effort, and individual projects and cores in P01 grant
applications are specified in the publication, "Program Project Grant
of the National Cancer Institute:  Guidelines, 1995," which may be
obtained from the NCI Referral Officer cited under the APPLICATION
PROCEDURES section above.
The anticipated date of award is March 1, 1997.
Scientific merit of the Program Project, as reflected by the priority
score; availability of funds; and programmatic priorities will be
considered in making awards pursuant to this RFA.
Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcomed.
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  20892-7328
Telephone:  (301) 496-8573
FAX:  (301)402-0553
Email:  PilchS@dcpcepn.nci.nih.gov
Victor A. Fung, Ph.D.
Division of Cancer Biology
National Cancer Institute
Executive Plaza North, Suite 700
BETHESDA MD  20892-7420
Telephone:  (301) 496-5471
FAX:  (301) 496-1040
Email:  FungV@epndce.nci.nih.gov
Direct inquiries regarding fiscal matters to:
Robert E. Hawkins
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
BETHESDA MD  20892-7150
Telephone:  (301) 496-7800  Ext. 213
FAX: (301) 496-8601
Email: HawkinsR@gab.nci.nih.gov
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, (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 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.

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