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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics
  • Case-Control Studies
  • DNA Adducts / adverse effects*
  • DNA Methylation*
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Odds Ratio
  • Polycyclic Aromatic Hydrocarbons / adverse effects*
  • Promoter Regions, Genetic
  • Risk Factors


  • DNA Adducts
  • Polycyclic Aromatic Hydrocarbons
  • polycyclic aromatic hydrocarbons-DNA adduct