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ABSTRACT: Prevalence and Spectrum of p53 Mutations Associated
with Smoking in Breast Cancer
To explore the role of smoking in breast cancer, we undertook
a population-based study to evaluate the prevalence and spectrum
of p53 mutations in the breast tumors of smokers and nonsmokers.
We evaluated 456 archival invasive breast tumors for mutations
in exons 4-8 of the p53 gene, using single-strand conformational
polymorphism analysis and manual sequencing.
Statistical analyses
were performed to determine the association of p53 mutations
with clinical and smoking characteristics. Of 108 mutations identified,
77 (71%) were point mutations and 31 (29%) were deletions or
insertions.
A higher prevalence of p53 mutations was found in
the breast tumors of current smokers (36.5%; P = 0.02) compared
with never smokers (23.6%), whereas fewer mutations were found
in former smokers (16.2%; P = 0.09).
After adjustment for age,
race, menopausal status, clinical stage, tumor size, and family
history of breast cancer, current smokers were significantly
more likely to harbor any p53 mutation [odds ratio (OR), 2.11;
95% confidence interval (CI), 1.17-3.78], p53 transversions
(OR, 3.37; 95% CI, 1.03-11.06), and G:CT:A transversions
(OR, 10.53; 95% CI, 1.77-62.55) compared with never smokers.
Stage at diagnosis did not account for the increase in p53 mutation-positive
breast cancer among current smokers.
Former smokers were also
more likely than never smokers to harbor G:CT:A transversions
(OR, 2.43; 95% CI, 0.37-15.73), although this association
was not statistically significant.
Among former smokers, the
prevalence of p53 mutations varied with time since quitting:
former smokers who quit smoking for longer than 1 year had a
lower prevalence of p53 mutations (10.5% for 1-5 years and
12.9% for >5 years) than those who had stopped smoking within
the year of their cancer diagnosis (26.3%).
Our results indicate
that cigarette smoking appears to modify the prevalence and spectrum
of p53 mutations in breast tumors.
Moreover, the difference in
mutational spectra observed between smokers and nonsmokers is
suggestive of the genotoxic effects of smoking in breast tissue.
[04/03/2002; Cancer Research]
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