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

被引:0
|
作者
Conway, K
Edmiston, SN
Cui, L
Drouin, SS
Pang, JZ
He, M
Tse, CK
Geradts, J
Dressler, L
Liu, ET
Millikan, R
Newman, B
机构
[1] Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Epidemiol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA
[4] Natl Canc Inst, Comparat Mol Pathol Unit, Gaithersburg, MD 20877 USA
[5] Roswell Pk Canc Inst, Dept Pathol & Lab Med, Buffalo, NY 14263 USA
[6] Natl Univ Singapore, Genome Inst Singapore, Singapore 117640, Singapore
[7] Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld 4059, Australia
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中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 p,53 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 vi ere 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 I 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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页码:1987 / 1995
页数:9
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