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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
New CalEPA report and Breast Cancer

http://www.arb.ca.gov/toxics/ets/finalreport/finalreport.htm

mammary carcinogens in tobacco smoke

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
biology
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.
biology contd
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
biology contd5
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

exposure misclassification
Exposure misclassification
  • Biases results towards null
  • Probably reason for differences in Hirayama and Garfinkle study
  • Important in studies of SHS
shs and breast cancer in younger premenopausal women
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.
utilizing unexposed referent raises risk estimate within study comparison morabia et al 1996
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)

slide14
Comparison of breast cancer risk from active and passive smoke exposure in studies CalEPA considered most informative
thun s arguments
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
evidence for breast cancer in younger women stronger than lung cancer in 1986
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
passive smoking and lung cancer
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
implications for workplace exposure of waitresses
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
write down this url
Write down this URL
  • http://www.arb.ca.gov/toxics/ets/

finalreport/finalreport.htm