Project: Research project

Project Details


DESCRIPTION: To provide more effective aetiology-based strategy for cancer
prevention and control, the long-term objectives of this application are to:
1) evaluate the impact of defective cellular responses to DNA damage in
human breast cancer risk; 2) understand the genetic and non-genetic
modification of DNA-induced responses and cancer susceptibility; 3) identify
high-risk populations by using both traditional epidemiological risk factors
and laboratory measurements; and 4) reduce breast cancer risk by targeting
modifiable risk factors (viz., DNA repair capacity and cell proliferation).
The primary objective of the proposed research is to evaluate three specific
DNA-damage-inducible responses as biomarkers in breast cancer risk
assessment (viz., poly(ADP-ribose) polymerase (PARP), nucleotide excision
repair (NER), and cell cycle delay). Data from several small preliminary
human studies have suggested that these three biomarkers may play important
roles in the carcinogenesis pathway of human breast cancer as follows: 1)
PARP plays a critical role in blocking cells from proliferation in response
to DNA damage and allowing enough time for DNA repair to complete; 2) NER is
the most important repair mechanisms in response to a wide variety of DNA
damages; and 3) excessive accumulated unrepaired DNA damage may result in
prolonged cell cycle delay and consequently, apoptosis. The secondary
objective is to assess the mechanisms involved in the regulation of these
three responses to DNA damage by genetic and non-genetic factors. The
purpose is to identify individuals at risk through modifiable mechanisms.
It may then be possible to devise aetiology-based preventive strategies that
are more closely tailored to the specific defects conferring individual
risk. This approach may provide unique opportunities in cancer prevention
and control, particularly in high risk populations. The proposed study will
use a cancer case-control study design with a molecular epidemiological
approach. The study subjects include 200 incident breast cancer cases and
200 controls (matched by age and family history of breast cancer). A
self-administered questionnaire will be used to collect data on demographic
factors, family history of cancer, medication, ionizing radiation exposure,
and dietary intake. Mitogen-activated peripheral blood T lymphocytes will
be used for all the proposed laboratory measurements.
Effective start/end date9/12/978/31/02


  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute: $29,678.00
  • National Cancer Institute: $93,837.00
  • National Cancer Institute
  • National Cancer Institute: $22,711.00
  • National Cancer Institute: $106,430.00


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