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1.  Mutations in p53, p53 protein overexpression and breast cancer survival 
p53 is an important tumor-suppressor gene that encodes p53 protein, a molecule involved in cell cycle regulation, and has been inconsistently linked to breast cancer survival. Using archived tumor tissue from a population-based sample of 859 women diagnosed with breast cancer between 1996–1997, we determined p53 mutations in exons 5–8 and p53 protein overexpression. We examined the association of p53 mutations with overexpression and selected tumor clinical parameters. We assessed whether either p53 marker was associated with survival through 2002, adjusting for other tumor markers and prognostic factors. The prevalence of protein overexpression in the tumor was 36% (307/859) and any p53 mutation was 15% (128/859). p53 overexpression was positively associated with the presence of any p53 mutation (odds ratio (OR)=2.2, 95% confidence interval (CI)=1.5–3.2), particularly missense mutations (OR=7.0, 95%CI=3.6–13.7). Negative estrogen and progesterone receptor status (ER/PR) was positively associated with both p53 protein overexpression (OR = 2.6, 95% CI = 1.7–4.0), and p53 mutation (OR = 3.9, 95% CI = 2.4–6.5). Any p53 mutation and missense mutations, but not p53 protein overexpression, were associated with breast cancer-specific mortality (Hazard ratio HR=1.7, 95%CI=1.0–2.8; HR=2.0, 95%CI=1.1–3.6, respectively) and all-cause mortality (HR=1.5, 95%CI=1.0–2.4; HR=2.0, 95%CI=1.2–3.4, respectively); nonsense mutations were associated only with breast cancer-specific mortality (HR=3.0, 95%CI=1.1–8.1). These associations however did not remain after adjusting for ER/PR status. Thus, in this population-based cohort of women with breast cancer, although p53 protein overexpression and p53 mutations were associated with each other, neither independently impacted breast-cancer specific or all-causing mortality after considering ER/PR status.
PMCID: PMC2832100  PMID: 19602056
breast cancer; p53 mutations; p53 overexpression; survival
2.  Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors 
Environmental Health Perspectives  2009;118(4):511-518.
Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology.
We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number.
We examined this possibility in a population-based case–control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing.
We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH–DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation–negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11–2.15] but not p53 mutation–positive (OR = 0.77; 95% CI, 0.43–1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C→A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects.
These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation.
PMCID: PMC2854728  PMID: 20064791
breast cancer; p53 mutation; p53 overexpression; PAH; polycylic aromatic hydrocarbons

Results 1-2 (2)