Full Text CA-96-002
 
DIETARY EXPOSURE TO AND EFFECTS OF PLANT FOOD CONSTITUENTS
 
NIH GUIDE, Volume 25, Number 1, January 26, 1996
 
RFA:  CA-96-002
 
P.T. 34

Keywords: 
  Nutrition/Dietetics 
  Cancer/Carcinogenesis 
  Disease Prevention+ 

 
National Cancer Institute
 
Letter of Intent Receipt Date:  February 20, 1996
Application Receipt Date:  April 18, 1996
 
PURPOSE
 
The Division of Cancer Prevention and Control, National Cancer
Institute (NCI) seeks to encourage investigator-initiated research
project grants (R)1) to assess dietary exposure to constituents of
plant foods that may affect cancer risk and to assess their
biological effects relative to cancer prevention in humans.  The
ultimate goal of the research to be supported is to increase
knowledge of the role of plant food constituents in order to refine
dietary guidance for the prevention of cancer in the population.
 
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), "Dietary Exposure to and Effects of Plant
Food Constituents" 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 "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
 
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.
 
MECHANISMS OF SUPPORT
 
This RFA will use the National Institutes of Health (NIH) research
project grant (R01) as the mechanism of support.
 
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 September
20, 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 $2.0 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 eight to ten 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
 
Epidemiologic investigations (ecologic, cohort, and case-control
studies) have shown remarkable consistency in finding lower risk for
a variety of cancers among populations consuming large amounts of
plant foods, particularly fruits and vegetables.  The association is
most marked for epithelial cancers, especially those of the
alimentary and respiratory tracts, and is weaker for
hormone-dependent cancers.  The inverse association with cancer risk
has been observed for a wide variety of dietary guidelines for
Americans that encourage consumption of fruits and vegetables.  They
have also spurred development and expansion of the National Five A
Day for Better Health program, a public-private partnership between
the NCI and the Produce for Better Health Foundation to encourage
Americans to consume at least five servings of fruits and vegetables
daily.
 
A large number of naturally occurring nutritive and non-nutritive
constituents present in vegetables, fruits, and grain products has
been shown to inhibit carcinogenesis in animals when fed in purified
form and at pharmacologic levels.  These include carotenoids; vitamin
C; vitamin E; folic acid; selenium; dietary fiber; dithiolthiones,
glucosinolates, indoles, isothiocyanates, and thiocyanates (found in
cruciferous vegetables); coumarins; flavonoids; phenols; protease
inhibitors (found in seeds and legumes); plant sterols; isoflavones;
saponins; inositol hexaphosphate; allium compounds (found in onions,
garlic, and chives); and limonene.  Little information is available
on the levels in food and the dietary intake of non-nutrient
constituents of plant foods; the metabolism of plant food
constituents in humans; the ability of various plant food
constituents, when consumed at levels that can be obtained from foods
in the diet, to modify cancer risk; and the mechanisms of action of
their putative anticarcinogenic effects.  Even less is known about
interactions among the various plant constituents and with other
components of the diet.  Expansion of ongoing research is needed to
proved a better understanding of the potential impacts of various
constituents of plant foods on human cancer prevention, including
information on dietary exposure, metabolism, and mechanisms of
action. Such information should aid in refining dietary guidance on
the amounts and types of plant foods that have the potential to
reduce cancer risk.
 
Specific Objectives
 
Applications for multidisciplinary, investigator-initiated research
project grants (RO1) examining plant food constituents that may
mediate the cancer preventive effects of diets high in fruits and
vegetables are encouraged by this RFA.  Studies to develop
methodologies for the identification and quantification of such
non-nutrient constituents in food will be considered, as will studies
to develop improved analytical methods for the identification and
quantification of plant food constituents and their metabolites in
biological specimens.  Encompassed within the scope of this RFA are
assessments of food composition and dietary exposure to non-nutrient
plant food constituents, as well as the development of biomarkers for
exposure to plant food constituents.  Also encouraged are studies of
plant constituents' biological activity, absorption, metabolism, and
mechanisms of action and interactions for cancer prevention in
humans.  Although the major emphasis of this RFA is to address the
effects of foods and diet in human subjects, the use of animal models
may be considered provided its relevance to human cancer prevention
can be justified.  Proposed studies that include use of purified
compounds should be designed to assess levels that can be obtained
from foods in the diet, rather than nonphysiologic levels.
 
Some (non-exhaustive) examples of relevant research areas are as
follows:
 
o  Determining the amounts of non-nutritive constituents in plant
foods and the amounts consumed in typical diets;
 
o  Elucidating molecular and cellular mechanisms of actions for
possible anticarcinogenic effects of plant food constituents;
 
o  Examining the impact of interactions among various plant food
constituents on their role(s) in cancer prevention;
 
o  Defining dose-response relationships for nutrient and non-nutrient
plant food constituents on molecular and cellular events and
alterations in metabolic pathways;
 
o  Identifying biochemical markers as quantitative measures of plant
food intake, digestion, absorption, metabolic breakdown of specific
nutrient and/or non-nutrient constituents; and
 
o  Determining the bioavailability of nutrient and non-nutrient plant
food constituents at various intakes and from different food sources.
 
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 February 20, 1996, 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:
 
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
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) 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, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910,
telephone 301/435-0714, email: girg@drgpo.drg.nih.gov; 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 is 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.
 
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 express/courier services)
 
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 express/courier services)
 
Applications must be received by April 18, 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.
 
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 no responsive to the RFA, it well 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 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 September 30, 1996.
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to
clarity 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:
 
Barbara A. Fisher
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800  Ext. 229
FAX:  (301) 496-8601
EMAIL:  FisherB@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 Services 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 Public Health Service (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
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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