Grant Details
Grant Number: |
5R01CA073730-02 Interpret this number |
Primary Investigator: |
Rebbeck, Timothy |
Organization: |
University Of Pennsylvania |
Project Title: |
Etiologic Heterogeneity in Late Onset Breast Cancer |
Fiscal Year: |
1998 |
Abstract
DESCRIPTION: (Adapted from Applicant's Abstract). Late-onset breast cancer
is probably caused by the interaction of multiple genes, endogenous
environments, and exogenous exposures. One consequence of this complex,
multifactorial aetiology of breast cancer is that aetiologic heterogeneity
may exist. Aetiologic heterogeneity implies that two or more groups of
breast cancer cases in the general population are caused by different sets
of aetiological events. The ability to define aetiologically-distinct
(i.e., homogeneous) subgroups in the population may facilitate: 1)
epidemiological studies to identify causative agents in breast cancer
aetiology; 2) identification of optimal breast cancer diagnosis or treatment
regimens; and 3) the targeted application of cancer detection and prevention
strategies.
A case-series study is proposed, that will focus on aetiologic heterogeneity
in late onset breast cancer. This study will address three specific
hypotheses. First, candidate susceptibility genotypes at the cytochromes
P450 and glutathione-S-transferase loci will be evaluated for their capacity
to define aetiologically heterogeneous case groups with respect to age at
breast cancer diagnosis. Second, candidate genotypes will be evaluated for
their capacity to define aetiologically heterogeneous case groups with
respect to somatic genetic damage. Third, interactions of candidate
susceptibility genotypes and somatic genetic mutation will be evaluated for
their capacity to define aetiologically heterogeneous case groups.
In order to address these hypotheses, a study will be conducted, using an
existing subject accrual system to identify a sample of 600 incident,
invasive breast cancer cases at the Hospital of the University of
Pennsylvania (HUP). Risk factor information will be obtained from a
questionnaire interview, a biosample containing DNA will be collected using
a non-invasive cheek swab method, and pathology information will be
collected using a standardized medical record abstraction approach. In
addition, breast tumor and normal tissue will be obtained from half of these
subjects for loss of constitutional heterozygosity analysis. The results of
these analyses will be used to attempt to elucidate the complex,
multifactorial aetiology of late onset breast cancer.
Publications
Genetic Polymorphisms In Human Sult1a1 And Ugt1a1 Genes Associate With Breast Tumor Characteristics: A Case-series Study
Authors: Shatalova E.G.
, Walther S.E.
, Favorova O.O.
, Rebbeck T.R.
, Blanchard R.L.
.
Source: Breast Cancer Research : Bcr, 2005; 7(6), p. R909-21.
PMID: 16280036
Related Citations
Modification Of Brca1- And Brca2-associated Breast Cancer Risk By Aib1 Genotype And Reproductive History
Authors: Rebbeck T.R.
, Wang Y.
, Kantoff P.W.
, Krithivas K.
, Neuhausen S.L.
, Godwin A.K.
, Daly M.B.
, Narod S.A.
, Brunet J.S.
, Vesprini D.
, et al.
.
Source: Cancer Research, 2001-07-15 00:00:00.0; 61(14), p. 5420-4.
PMID: 11454686
Related Citations
Inherited Genetic Predisposition In Breast Cancer. A Population-based Perspective
Authors: Rebbeck T.R.
.
Source: Cancer, 1999-12-01 00:00:00.0; 86(11 Suppl), p. 2493-501.
PMID: 10630175
Related Citations
Collection Of Genomic Dna By Buccal Swabs For Polymerase Chain Reaction-based Biomarker Assays
Authors: Walker A.H.
, Najarian D.
, White D.L.
, Jaffe J.F.
, Kanetsky P.A.
, Rebbeck T.R.
.
Source: Environmental Health Perspectives, 1999 Jul; 107(7), p. 517-20.
PMID: 10378997
Related Citations
Modification Of Clinical Presentation Of Prostate Tumors By A Novel Genetic Variant In Cyp3a4
Authors: Rebbeck T.R.
, Jaffe J.M.
, Walker A.H.
, Wein A.J.
, Malkowicz S.B.
.
Source: Journal Of The National Cancer Institute, 1998-08-19 00:00:00.0; 90(16), p. 1225-9.
PMID: 9719084
Related Citations
Evaluation Of Genotype Data In Clinical Risk Assessment: Methods And Application To Brca1, Brca2, And N-acetyl Transferase-2 Genotypes In Breast Cancer
Authors: Rebbeck T.R.
, Rogatko A.
, Viana M.A.
.
Source: Genetic Testing, 1997-1998; 1(3), p. 157-64.
PMID: 10464641
Related Citations