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ABSTRACT: Organochlorines, p53 mutations in relation to breast
cancer risk and survival: A Danish cohort-nested case-controls
study
Epidemiological studies integrating genetic susceptibility
with biological measurements of organochlorine exposure may provide
new clues regarding these substances influence on breast cancer
etiology.
Initial attempts pursuing this avenue has dealt with
polymorphisms in the carcinogen-metabolizing enzymes cytochrome
P450 (CYPlAl). This study examined if mutations in the tumor
suppressor gene p53 affected organochlorine exposure related
breast cancer risk and survival.
The material consisted of 162
breast cancer cases and 316 matched controls, who had participated,
in the Copenhagen City Heart Study (CCHS) between 1976 and 1978.
Cases diagnosed between study initiation and 1993 were identified
by linkage to the Danish Cancer Registry. The case group served
as a cohort in the survival analyses.
Information on known and
suspected breast cancer risk factors was obtained from CCHS,
and the Danish Breast Cancer Cooperative Group provided information
on tumor characteristics. Lipid adjusted serum concentrations
of selected organochlorines were compared between cases and controls
while stratifing by p53 mutation status. A non-significant increased
risk of breast cancer was observed in the highest exposure level
of dieldrin and polychlorinated biphenyls among women who developed
a tumor with mutant p53 (odds ratio (OR)=3.53, 95% confidence
interval (CI)=0.79-15.79 and OR=3.00, 95% CI=0.66-13.62).
There
was no clear difference in overall survival between breast cancer
cases with "wild-type" and mutant p53, although a significant
dose-response relationship appeared for dieldrin exposure in
tumors with "wild-type" p53.
These preliminary results suggest
that p53 mutations may have a modifying effect on at least the
breast cancer risk associated with exposures to organochlorines.
[12/26/2001; Breast Cancer Research and Treatment]
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