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Purpose: Tobacco smoke exposure has been associated with altered DNA methylation. However, there is a paucity of information regarding tobacco smoke exposure and DNA methylation of breast tumors.Methods: We conducted a case-only analysis using breast tumor tissue from 493 postmenopausal and 225 premenopausal cases in the Western New York Exposures and Breast Cancer (WEB) study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A, CCND2, BRCA1, FHIT, and SYK) was measured with pyrosequencing. Participants reported their secondhand smoke (SHS) and active smoking exposure for seven time periods. Unconditional logistic regression was used to estimate odds ratios (OR) of having methylation higher than the median.Results: SHS exposure was associated with tumor DNA methylation among postmenopausal but not premenopausal women. Active smoking at certain ages was associated with increased methylation of GSTP1, FHIT, and CDKN2A and decreased methylation of SCGB3A1 and BRCA1 among both pre- and postmenopausal women.Conclusion: Exposure to tobacco smoke may contribute to breast carcinogenesis via alterations in DNA methylation. Further studies in a larger panel of genes are warranted. [ABSTRACT FROM AUTHOR]

Background: The mechanism of the observed association between body mass, particularly centralized body fat, and postmenopausal breast cancer risk is not well understood. Objective: We hypothesized that body mass may affect DNA methylation through increased estrogen and chronic inflammation. The association between body mass and promoter methylation in breast tumors was investigated in a population-based, case-control study. Design: The promoter methylation of E-cadherin, p16, and RAR-β2 genes was assessed in breast tumor blocks from 803 pre- and postmenopausal cases by using real-time methylation-specific polymerase chain reaction. Unconditional logistic regression was used to derive the adjusted OR and 95% CI for case-case comparisons of tumors with and without promoter methylation of the genes. Results: The frequency of promoter methylation was 20% for E-cadherin, 25.9% for p16, and 27.5% for RAR-β2. There was no difference in the prevalence of the DNA methylation of individual genes by BMI, waist-to-hip ratio (WHR), or lifetime weight change between the age of 20 y and the present. However, in a case-case comparison of postmenopausal breast cancer, a greater WHR was associated with an increased likelihood of ≥1 of the 3 genes being methylated (OR: 1.85; 95% CI: 1.10, 3.11; P-trend < 0.02). Conclusions: We showed that WHR was associated with DNA promoter methylation of ≥1 of 3 genes in postmenopausal breast tumors. It may be that the association of body fat composition and postmenopausal breast cancer is related to altered DNA methylation. However, future studies in other populations and with an examination of the methylation of more genes are needed. [ABSTRACT FROM AUTHOR]

Objective: Chronic inflammation is suspected to have a role in breast carcinogenesis. Results of studies of non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer have been inconsistent. Timing of exposure and analysis of individual NSAIDs should be considered.Methods: We conducted a population-based case-control study in western New York State between 1996 and 2001. Cases, 35-79 years, had incident, primary, histologically confirmed breast cancer (n = 1,170). Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (>or=65 years). Participants were queried on use of aspirin, ibuprofen, and acetaminophen in the year prior and on aspirin during adulthood. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).Results: Recent aspirin use was inversely associated with breast cancer risk (adjusted OR 0.80, 95% CI: 0.68-0.94); the strongest reduction in risk was observed among those who took >or=2 pills/day on days that aspirin was taken (OR 0.74, 95% CI: 0.61-0. 90). Adult lifetime use was also associated with breast cancer risk (>10 days/month, adjusted OR 0.68, 95% CI: 0.46-1.00). Use of ibuprofen or acetaminophen was not associated with breast cancer.Conclusions: This is the first study to investigate the association of adult lifetime aspirin intake with breast cancer risk. Our findings provide evidence that aspirin use throughout a woman's life may confer some benefit. [ABSTRACT FROM AUTHOR]