Prevalence and spectrum of p53 mutations associated with smoking in breast cancer

Conway, Kathleen, Edmiston, Sharon N., Cui, Lisa, Drouin, S. Scott, Pang, Jingzhong, He, Mei, Tse, Chiu-Kit, Geradts, Joseph, Dressler, Lynn, Liu, Edison T., Millikan, Robert, & Newman, Beth M. (2002) Prevalence and spectrum of p53 mutations associated with smoking in breast cancer. Cancer Research, 62(7), pp. 1987-1995.

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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:C-->T: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:C-->T: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.

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ID Code: 9267
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: Mutation, Breast Neoplasms/, etiology Breast Neoplasms/, genetics Genes, p53/, genetics Smoking/, adverse effects Smoking/, genetics Adult, Aged, Breast Neoplasms/epidemiology, Case, Control Studies, DNA Mutational Analysis, Female, Humans, Middle Aged, North Carolina/epidemiology, Polymorphism, Single, Stranded Conformational, Prevalence, Risk Factors, Smoking/epidemiology
ISSN: 1538-7445
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Oncology and Carcinogenesis not elsewhere classified (111299)
Divisions: Current > Research Centres > Centre for Health Research
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2002 American Association for Cancer Research
Deposited On: 03 Sep 2007 00:00
Last Modified: 28 Jan 2015 02:06

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