Associations between polycyclic aromatic hydrocarbon-related exposures and p53 mutations in breast tumors.
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.
Mordukhovich
Irina
I
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7435, USA. irinam@email.unc.edu
Rossner
Pavel
P
Terry
Mary Beth
MB
Santella
Regina
R
Zhang
Yu-Jing
YJ
Hibshoosh
Hanina
H
Memeo
Lorenzo
L
Mansukhani
Mahesh
M
Long
Chang-Min
CM
Garbowski
Gail
G
Agrawal
Meenakshi
M
Gaudet
Mia M
MM
Steck
Susan E
SE
Sagiv
Sharon K
SK
Eng
Sybil M
SM
Teitelbaum
Susan L
SL
Neugut
Alfred I
AI
Conway-Dorsey
Kathleen
K
Gammon
Marilie D
MD
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
D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53; C095911:polycyclic aromatic hydrocarbons-DNA adduct