PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk.
BACKGROUND
Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker.


OBJECTIVE
We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking.


METHODS
We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH-DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973).


RESULTS
Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13-2.16] for detectable PAH-DNA adducts and 0.93 (95% CI, 0.56-1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82-1.69) for ever smokers and 1.44 (95% CI, 0.97-2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively).


CONCLUSIONS
We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.
McCarty
Kathleen M
KM
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. kathleen.mccarty@yale.edu
Santella
Regina M
RM
Steck
Susan E
SE
Cleveland
Rebecca J
RJ
Ahn
Jiyoung
J
Ambrosone
Christine B
CB
North
Kari
K
Sagiv
Sharon K
SK
Eng
Sybil M
SM
Teitelbaum
Susan L
SL
Neugut
Alfred I
AI
Gammon
Marilie D
MD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D011110:Polymorphism, Genetic; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012907:Smoking
D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D005982:Glutathione Transferase