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New CalEPA report and Breast Cancer

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

ARB Public Hearing to Decide if TAC

ARB Public Hearing to Decide if TAC

ScientificReview Panel

ScientificReview Panel

Prioritization/SelectionToxic Substance

OEHHAHealth Evaluation

ARBExposure

Assessment

Draft ReportPublic Workshop/

Comments

Draft ReportPublic Workshop/

Comments

Toxic Air Contaminants ProgramToxic Air Contaminants Program IdentificationIdentification

Mammary Carcinogens in Tobacco Smoke

Aromatic hydrocarbonsBenzeneBenzo[a]pyreneDibenz[a,h]anthraceneDibenzo[a,e]pyreneDibenzo[a,h]pyreneDibenzo[a,I]pyreneDibenzo[a,l]pyrene  NitrosaminesN-nitrosodiethylamineN-Nitrosodi-n-butyl-amine

Aliphatic compoundsAcrylamideAcrylonitrile1,3-ButadieneIsopreneNitromethanePropylene oxideUrethaneVinyl chloride Arylamines and nitrarenes4-AminobiphenylNitrobenzeneOrtho-Toluidine

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)

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 Morabia A., Environmental and Molecular Mutagenesis 39:89-95 2002

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 nonsmokersMorabia A., Environmental and Molecular Mutagenesis 39:89-95 2002

Problems with exposure assessment

Effect of Exposure Misclassification on Estimates of Relative Risk

0123456789

10

# Cases/1000 People Exposed

Not Exposed

Relative Risk:

10002

100010

= 5

Effect of Exposure Misclassification on Estimates of Relative Risk

0123456789

10

# Cases/1000 People

True Mis-

Classification

ExposedNot Exposed

Relative Risk:

10002

100010

= 58

10004

1000

= 2

SHS Breast Cancer Risk

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(95%

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Premenopausal Postmenopausal

Solid symbols designate studies OEHHA considered most informative

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)

Exposure

Smokers vs non-smokers

with no ETS

Smokers vs non-smokers

(includes ETS exposed)

Active 1-9 cpd 2.2 (1.0; 4.4) 1.2 (0.8; 2.0)

10-19 cpd 2.7 (1.4; 5.4) 1.7 (1.1; 2.5)

≥ 20 cpd 4.6 (2.2; 9.7) 1.9 (1.2; 2.9)

Ever passive 3.2 (1.7; 5.9)

(Similar within study comparison results in Johnson et al., 2000,

Lash and Aschengrau, 1999, and Kropp and Chang Claude, 2002)

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

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Active Passive

Arguments Raised 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

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

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

What if you are wrong? Type I (false positive)

Women unnecessarily alarmed about passive smoking and breast cancer

Tobacco industry attacks Type II (false negative)

Young women die of breast cancer Tobacco industry quotes ACS

Where to read the full CalEPA report http://www.arb.ca.gov/toxics/ets/ finalreport/finalreport.htm Passive smoking and breast cancer starts

on page 7-76 of Part B Active smoking and breast cancer in

Appendix 7A Discussion on exposure missclassification

and criteria for causality in Chapter 1 of Part B

What Can You Do?

For scientists: Read the report and make your views known

For advocates: Use the data. CalEPA has a reputation for being first, ahead of the ACS and CDC, and being right.