New CalEPA report and Breast Cancer

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New CalEPA report and Breast Cancer
http//www.arb.ca.gov/toxics/ets/finalreport/final
report.htm
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Mammary Carcinogens in Tobacco Smoke
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Biology

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

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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 3989-95 2002

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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 3989-95 2002

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Problems with exposure assessment
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Effect of Exposure Misclassification on Estimates
of Relative Risk
Relative Risk
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Effect of Exposure Misclassification on Estimates
of Relative Risk
Relative Risk
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Effect of Exposure Misclassification on Estimates
of Relative Risk
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Relative Risk
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Exposure misclassification

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

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SHS Breast Cancer Risk
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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.

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

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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

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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

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(No Transcript)
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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

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Write down this URL

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