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

Publication ,  Journal Article
Conway, K; Edmiston, SN; Cui, L; Drouin, SS; Pang, J; He, M; Tse, C-K; Geradts, J; Dressler, L; Liu, ET; Millikan, R; Newman, B
Published in: Cancer Res
April 1, 2002

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 2002

Volume

62

Issue

7

Start / End Page

1987 / 1995

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Prevalence
  • Polymorphism, Single-Stranded Conformational
  • Oncology & Carcinogenesis
  • North Carolina
  • Mutation
  • Middle Aged
  • Humans
  • Genes, p53
 

Citation

APA
Chicago
ICMJE
MLA
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Conway, K., Edmiston, S. N., Cui, L., Drouin, S. S., Pang, J., He, M., … Newman, B. (2002). Prevalence and spectrum of p53 mutations associated with smoking in breast cancer. Cancer Res, 62(7), 1987–1995.
Conway, Kathleen, Sharon N. Edmiston, Lisa Cui, S Scott Drouin, Jingzhong Pang, Mei He, Chiu-Kit Tse, et al. “Prevalence and spectrum of p53 mutations associated with smoking in breast cancer.Cancer Res 62, no. 7 (April 1, 2002): 1987–95.
Conway K, Edmiston SN, Cui L, Drouin SS, Pang J, He M, et al. Prevalence and spectrum of p53 mutations associated with smoking in breast cancer. Cancer Res. 2002 Apr 1;62(7):1987–95.
Conway, Kathleen, et al. “Prevalence and spectrum of p53 mutations associated with smoking in breast cancer.Cancer Res, vol. 62, no. 7, Apr. 2002, pp. 1987–95.
Conway K, Edmiston SN, Cui L, Drouin SS, Pang J, He M, Tse C-K, Geradts J, Dressler L, Liu ET, Millikan R, Newman B. Prevalence and spectrum of p53 mutations associated with smoking in breast cancer. Cancer Res. 2002 Apr 1;62(7):1987–1995.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 2002

Volume

62

Issue

7

Start / End Page

1987 / 1995

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Prevalence
  • Polymorphism, Single-Stranded Conformational
  • Oncology & Carcinogenesis
  • North Carolina
  • Mutation
  • Middle Aged
  • Humans
  • Genes, p53