Academic journal article Environmental Health Perspectives

Associations between Polycyclic Aromatic Hydrocarbon-Related Exposures and P53 Mutations in Breast Tumors

Academic journal article Environmental Health Perspectives

Associations between Polycyclic Aromatic Hydrocarbon-Related Exposures and P53 Mutations in Breast Tumors

Article excerpt

BACKGROUND: 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.

OBJECTIVES: We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number.

METHODS: 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.

RESULTS: 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[right arrow]A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects.

CONCLUSIONS: 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.

KEY WORDS: breast cancer, p53 mutation, p53 overexpression, PAH, polycylic aromatic hydrocarbons. Environ Health Perspect 118:511-518 (2010). doi:10.1289/ehp.0901233 [Online 18 November 2009]

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Breast cancer is the second leading cancer-related cause of death among women in the United States (American Cancer Society 2008). Previous epidemiologic and experimental investigations suggest that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer (Bonner et al. 2005; el-Bayoumy et al. 1995; Gammon et al. 2002b, 2004b; Rundle et al. 2000). However, despite strongly positive associations in animal models and some evidence of a positive association in humans, the carcinogenicity of these chemical compounds on the human breast remains unclear.

PAHs ate ubiquitous environmental pollutants formed by incomplete combustion of organic material (Samanta et al. 2002). These chemicals have estrogenic properties (Santodonato 1997), are known carcinogens in humans (Samanta et al. 2002), and cause mammary tumors in laboratory animals (el-Bayoumy et al. 1995; Hecht 2002). Exposure to PAHs in the general population occurs primarily through charred, smoked, and broiled foods; leafy vegetables (Phillips 1999); wood- and coal-burning stoves (Lewis et al. 1999); air pollution (Lioy and Greenberg 1990); and tobacco smoke (Besaratinia et al. 2002). PAH-DNA adducts (Gammon et al. 2004b), lifetime intake of grilled/smoked meat (Steck et al. 2007), and long-term passive smoking--but not current or former active smoking (Gammon et al. 2004a)--have been associated with breast cancer in out study population.

Cigarette smoke is associated with PAH-DNA adducts in human lymphocytes (Shantakumar et al. 2005), and the PAH benzo[a]pyrene (B[a]P) from cigarette smoke induces neoplastic transformation of human breast epithelial cells (Russo et al. 2002). However, smoking has been inconsistently linked to breast cancer in epidemiologic research, with more consistently positive findings repotted for long-term passive smoking and among genetically susceptible subgroups (Ambrosone et al, 2008; Terry and Goodman 2006; Terry and Rohan 2002). …

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