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PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk
McCarty, K. M., Santella, R. M., Steck, S. E., Cleveland, R. J., Ahn, J., Ambrosone, C. B., North, K., Sagiv, S. K., Eng, S. M., Teitelbaum, S. L., Neugut, A. I., Gammon, M. D. Environ Health Perspect. 2009. 117:4, 552-8.
Topic area
Environmental pollutant - PAH
Study design
Population based case-control
Funding agency
NCI NIEHS
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analysis based on menopausal status
Number of Controls
Controls: 941
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Female residents of Nassau and Suffolk Counties (Long Island), NY, participating in the Long Island Breast Cancer Study Project, age 20 or older, English-speaking, newly diagnosed with in situ or invasive breast cancer in 1996-1997. Cases identified by regional hospital pathology laboratories. Controls had no breast cancer history and were matched by 5-year age group, identified by random-digit-dialing or Medicare records (for women 65 and older). Approximately 1102 cases (73.1% of LIBCSP cases) and 1140 controls (73.3% of LIBCSP controls) provided a blood sample; the analyses reported here were limited to women for whom PAH-DNA adducts were assessed in blood samples and for whom samples could be sufficiently genotyped, which is reflected in the number of cases/controls reported above. The main reason that samples could not be genotyped (<10%) was insufficient DNA.
Comment about participation selection
In the LIBCSP, giving a blood sample was positively associated with being white, ever using alcohol, ever using HRT, ever having a mammography, and lactation history. Older women and former smokers were less likely to give blood. Blood donation was not associated with case-control status, so these differences between the total study population and the sub-population who donated blood should not bias the findings, but could affect generalizability.
Exposure Investigated
Exposures investigated
PAH-DNA adducts were measured by competitive enzyme linked immunosorbent assay (ELISA) in blood samples obtained near time of diagnosis/reference. Samples with <15% inhibition were considered non-detect. GSTT1 and GSTM1 polymorphisms in blood by multiple
How exposure was measured
Biological Questionnaire, in person
Exposure assessment comment
PAH-DNA adducts reflect recent exposure. Blood obtained after diagnosis may not capture the relevant etiologic period. The relationship of PAH-DNA adducts to specific exposure sources is poorly understood, so this measure may not correctly rank the exposures relevant to disease. GSTs are enzymes involved in the activation and deactivation of PAH intermediates.
Breast cancer outcome investigated
Primary incident breast cancer
DCIS/LCIS
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Age at reference, race, family history, parity, age at menarche, age at first pregnancy, menopausal status, lifetime alcohol use, education, smoking status, and age at diagnosis.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Yes
Strength of associations reported
GSTT1 genotype:
Wildtype (present), detectable vs non-detectable PAH-DNA adducts: aOR 1.01 (95% CI 0.87-1.19)
Variant (null), detectable vs non-detectable PAH-DNA adducts: aOR 1.14 (95% CI 0.87-1.48)

GSTM1 genotype:
Wildtype (present), detectable vs non-detectable PAH-DNA adducts: aOR 0.99 (95% CI 0.82-1.19)
Variant (null), detectable vs non-detectable PAH-DNA adducts: aOR 1.13 (95% CI 0.93-1.37)

GSTP1 genotype:
Homozygous wildtype AA, detectable vs non-detectable PAH-DNA adducts: aOR 0.94 (95% CI 0.78-1.13)
Variant AG or GG, detectable vs non-detectable PAH-DNA adducts: aOR 1.15 (95% CI 0.95-1.38)

GSTA1 genotype:
Wildtype A*/A*, detectable vs non-detectable PAH-DNA adducts: aOR 0.97 (95% CI 0.78-1.20)
Variant A*/B* or B*/B*, detectable vs non-detectable PAH-DNA adducts: aOR 1.03 (95% CI 0.86-1.22)

The relative odds of breast cancer were significantly higher among individuals with three variant genotypes and detectable PAH-DNA adducts (aOR 1.56; 95% CI 1.13-2.16) than those with four common genotypes and non-detectable PAH-DNA adducts (aOR 0.93; 95% CI 0.56-1.56). However, the interaction was not significant on the multiplicative scale (p-interaction = 0.43) or the additive scale (ICR = 0.75; 95% CI 0.20-1.30).
Results Comments
No significant interaction between genotypes and smoking status on detectable vs non-detectable PAHDNA adduct status.
Abstract
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). CONCLUSION: We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.
Author address
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. kathleen.mccarty@yale.edu
Controls participation rate
63% completed interview 46% both completed intervi
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