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New CalEPA report and Breast Cancer

New CalEPA report and Breast Cancer. http://www.arb.ca.gov/toxics/ets/finalreport/finalreport.htm. Aromatic hydrocarbons Benzene Benzo[a]pyrene Dibenz[a,h]anthracene Dibenzo[a,e]pyrene Dibenzo[a,h]pyrene Dibenzo[a,I]pyrene Dibenzo[a,l]pyrene Nitrosamines N-nitrosodiethylamine

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New CalEPA report and Breast Cancer

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  1. New CalEPA report and Breast Cancer http://www.arb.ca.gov/toxics/ets/finalreport/finalreport.htm

  2. Aromatic hydrocarbons Benzene Benzo[a]pyrene Dibenz[a,h]anthracene Dibenzo[a,e]pyrene Dibenzo[a,h]pyrene Dibenzo[a,I]pyrene Dibenzo[a,l]pyrene Nitrosamines N-nitrosodiethylamine N-Nitrosodi-n-butyl-amine Aliphatic compounds Acrylamide Acrylonitrile 1,3-Butadiene Isoprene Nitromethane Propylene oxide Urethane Vinyl chloride Arylamines and nitrarenes 4-Aminobiphenyl Nitrobenzene Ortho-Toluidine Mammary Carcinogens in Tobacco Smoke

  3. Biology • Tobacco smoke contains multiple fat-soluble compounds known to induce mammary tumors in rodents. (PAH’s, heterocyclic amines, aromatic amines, and nitro-PAH’s) • These carcinogens can be activated into electrophilic intermediates by enzymes active in the human breast epithelial cell.

  4. Biology (contd) • Genes coding for activation/detoxification enzymes (e.g. NAT2, NAT1, CYP1a1, COMT, BRCA1 And BRCA2) have been reported to modify the relationship of tobacco smoke to breast cancer risk (although results are inconsistent). • Electrophilic metabolites of tobacco compounds bind to DNA and form DNA adducts that can be detected in human breast epithelial cells.Morabia A., Environmental and Molecular Mutagenesis 39:89-95 2002

  5. Biology (contd) • Genomic alterations observed in vitro after exposure of human breast epithelial cells to tobacco carcinogens resemble those in familial breast cancer. • p53 damage in some breast tumors of smokers, but not nonsmokers Morabia A., Environmental and Molecular Mutagenesis 39:89-95 2002

  6. Problems with exposure assessment

  7. Effect of Exposure Misclassification on Estimates of Relative Risk Relative Risk: • = 5

  8. Effect of Exposure Misclassification on Estimates of Relative Risk Relative Risk: • = 5

  9. Effect of Exposure Misclassification on Estimates of Relative Risk • = 2 Relative Risk: • = 5

  10. Exposure misclassification • Biases results towards null • Probably reason for differences in Hirayama and Garfinkle study • Important in studies of SHS

  11. SHS Breast Cancer Risk

  12. SHS and Breast Cancer in Younger/Premenopausal Women • 14 studies evaluated breast cancer risk in younger/premenopausal women strata. • 13/14 found elevated risks (1.1-7.1), and 7 were statistically significant. • Pooled risk estimate from meta-analysis = 1.68 (95% CI 1.31-2.15). • Pooled risk estimate for studies with lifetime exposure information from all sources = 2.2 (95% CI 1.69-2.87) • Some evidence of dose-response.

  13. Utilizing Unexposed Referent Raises Risk Estimate(within study comparison, Morabia et al. 1996) (Similar within study comparison results in Johnson et al., 2000, Lash and Aschengrau, 1999, and Kropp and Chang Claude, 2002)

  14. Comparison of breast cancer risk from active and passive smoke exposure in studies CalEPA considered most informative

  15. Thun’s arguments • If active smoking does not cause breast cancer, how can passive smoking? • Active smoking does cause breast cancer • IARC says no effect • 2004 report based on meeting in 2001 • Considered essentially the same studies as CalEPA 1997 (which did not say SHS caused breast cancer) • Only considered 4 studies published between 2000 and 2002 • Surgeon General says no effect • 2004 report essentially completed in 2001 • Considered 5 studies published after 2000 • CalEPA considered 23 studies between 2000 and 2005 • Cohort studies negative

  16. Lung cancer 1986 11/13 elevated risk 5 significant 1/3 cohort studies significant Hirayama*, Garfinkle,Gillis No toxicology No molecular epi Breast cancer 2006 13/14 elevated risk 7 significant 1/3 cohort studies significant Hanaoka*, Reynolds, Wartenberg Positive toxicology Molecular epi Evidence for breast cancer in younger women stronger than lung cancer in 1986

  17. Passive smoking and lung cancer • First study, Hirayama 1981 • Cohort study in Japan • Nonsmoking women married to men who smoked • Few women smoked • Few women worked outside the home • Significant elevation in risk • ACS CPS study, Garfinkle • Cohort study in USA • Nonsignificant elevation in risk • Many women smoked and worked outside the home

  18. Implications for Workplace Exposure of Waitresses • Highest occupational exposure to SHS: 72.3% • These women tend to get exposed at the most vulnerable times • 1.7 relative risk • 30% of breast cancer in younger waitresses

  19. Write down this URL • http://www.arb.ca.gov/toxics/ets/ finalreport/finalreport.htm

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