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Cancer Causes Control. 2015 Dec;26(12):1791-802. doi: 10.1007/s10552-015-0672-7. Epub 2015 Sep 25.

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts and breast cancer: modification by gene promoter methylation in a population-based study.

Author information

1
Department of Epidemiology, University of North Carolina, CB#7435, McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA. whitea@unc.edu.
2
Departments of Preventive Medicine, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.
3
Departments of Oncological Science, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.
4
Departments of Pediatrics, Ichan School of Medicine at Mt. Sinai, New York, NY, USA.
5
Department of Epidemiology, University of North Carolina, CB#7435, McGavran-Greenberg Hall, Chapel Hill, NC, 27599-7435, USA.
6
Research Center for Translational Medicine, Shanghai East Hospital of Tongji University School of Medicine, Shanghai, China.
7
Department of Environmental Health Sciences, Columbia University, New York, NY, USA.
8
Department of Epidemiology, Columbia University, New York, NY, USA.
9
Department of Medicine, Columbia University, New York, NY, USA.
10
Department of Pathology, Columbia University, New York, NY, USA.

Abstract

PURPOSE:

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer incidence. Aberrant changes in DNA methylation may be an early event in carcinogenesis. However, possible relations between PAH-DNA adducts, methylation, and breast cancer are unknown. The objectives of this study were to (1) assess associations between PAH-DNA adducts, and breast cancer, stratified by DNA methylation markers and (2) examine interactions between adducts and DNA methylation in association with breast cancer and tumor subtype.

METHODS:

In a population-based case-control study, promoter methylation of 13 breast cancer-related genes was measured in tumor tissue (n = 765-851 cases). Blood DNA from breast cancer cases (n = 873) and controls (n = 941) was used to assess PAH-DNA adducts and global methylation. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI); and the ratio of the OR (ROR) was used to assess heterogeneity.

RESULTS:

Women with detectable PAH-DNA adducts and methylated RARβ (ROR 2.69, 95% CI 1.02-7.12; p for interaction = 0.03) or APC (ROR 1.76, 95% CI 0.87-3.58; p for interaction = 0.09) genes were more likely to have hormone receptor-positive tumors than other subtypes. Interactions with other methylation markers were not apparent (p ≥ 0.10). The association between adducts and breast cancer did not vary by methylation status of the tumor nor did adducts associate with global methylation in the controls.

CONCLUSIONS:

Gene-specific methylation of RARβ, and perhaps APC, may interact with PAH-DNA adducts to increase risk of hormone receptor-positive breast cancer. There was little evidence that adducts were associated with or interacted with other methylation markers of interest.

KEYWORDS:

Breast cancer; DNA methylation; Polycyclic aromatic hydrocarbons

PMID:
26407953
PMCID:
PMC4763714
DOI:
10.1007/s10552-015-0672-7
[Indexed for MEDLINE]
Free PMC Article

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