DNA REPAIR GENOTYPE AND PHENOTYPE IN BREAST CANCER RISK

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant):
This is an effort to relate polymorphisms in DNA repair to incidence of breast
cancer. Mutations in both the BER and HRR pathways are proposed to make an
individual more sensitive to ionizing radiation and breast cancer. Assays for
assessing decreased activity in these pathways will also be pursued. Our
long-term goal in cancer prevention is to identify high-risk populations by
using DNA repair markers and to design mechanistic-based prevention strategy
tailored to the specific risk profiles of individuals. Human cells are
constantly exposed to exogenous and endogenous carcinogens capable of causing
DNA damage. Efficient repair is critical in maintaining genome integrity and
genetic variability in DNA repair may influence individual's susceptibility to
cancer. Our working hypothesis is that polymorphism of DNA repair genes with
nonconservative amino acid substitution may lead to altered protein function
in DNA repair and elevated breast cancer risk. Various man-made therapeutic,
diagnostic, or occupational exposure to ionizing radiation have been linked to
human breast cancer risk. The variety of DNA lesions induced by IR are mainly
repaired by base excision repair (BER) and homologous recombinational repair
(HRR). Data from our pilot study support the hypothesis that polymorphisms of
genes in BER and HRR may be associated with hypersensitivity to ionizing
radiation and susceptibility to breast cancer. To achieve our long-term goal,
the primary objective of this study is to characterize DNA repair genotype and
phenotype in breast cancer risk assessment. The secondary objective is to
develop more specific activity assays for BER and HRR in order to evaluate the
functional significance of individual DNA repair genetic variant in response
to IR. This study will use existing genomic DNA, cryopreserved lymphocytes,
and questionnaire data collected in an ongoing NCI-funded (CA73629) breast
cancer case-control study. The study subjects will include 200 newly
diagnosed, untreated breast cancer cases and 200 controls (frequency-matched
to cases on race and age [equal to or less than 5 yrs]) recruited from Wake
Forest University Baptist Medical Center. A questionnaire was use to collect
information on established breast cancer risk factors. This proposed research
is exceptionally cost-effective and efficient since the most costly tasks
(e.g., recruitment and collection of samples and data) are supported by the
parent study. Viable lymphocytes will provide an extremely unique opportunity
to investigate the functional significance of DNA repair variants, which is
crucial in evaluating the usefulness of SNPs of DNA repair genes as
susceptibility markers.
StatusFinished
Effective start/end date4/1/019/30/03

Funding

  • National Cancer Institute: $72,250.00
  • National Cancer Institute: $72,313.00

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