title: Associations between polycyclic aromatic hydrocarbon-related exposures and p53 mutations in breast tumors.
abstract: 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.
  
  
  OBJECTIVE
  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-->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.
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7435, USA. irinam@email.unc.edu
authors.forename: Irina
authors.initials: I
authors.lastname: Mordukhovich
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossner
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Regina
authors.initials: R
authors.lastname: Santella
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Memeo
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mansukhani
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Long
authors.forename: Gail
authors.initials: G
authors.lastname: Garbowski
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Agrawal
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Susan E
authors.initials: SE
authors.lastname: Steck
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Sagiv
authors.forename: Sybil M
authors.initials: SM
authors.lastname: Eng
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.forename: Kathleen
authors.initials: K
authors.lastname: Conway-Dorsey
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53; C095911:polycyclic aromatic hydrocarbons-DNA adduct