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
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.
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