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The international journal for all the latest news and research
Online Power Point Presentation
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
0.1
1
10
100
Hir
ay
am
a 8
4
Sa
nd
ler
85
Sm
ith
94
Mo
rab
ia 9
6
Mill
ika
n 9
8
Zh
ao
99
De
lfin
o 0
0
Jo
hn
so
n 0
0
Wa
rte
nb
urg
00
Kro
pp
02
Sh
rub
so
le 0
4
Ga
mm
on
04
Re
yn
old
s 0
4a
Ha
na
ok
a 0
5
Hir
ay
am
a 8
4
Sa
nd
ler
85
Mill
ika
n 9
8
Zh
ao
99
De
lfin
o 0
0
Jo
hn
so
n 0
0
Ga
mm
on
02
Re
yn
old
s 0
4a
Ha
na
ok
a 0
5
Rel
ativ
e R
isk
(95%
CI)
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
0.1
1
10S
mit
h
Mo
rab
ia
Zh
ao
Joh
nso
n
Kro
pp
Han
aoka
Sm
ith
Mo
rab
ia
Zh
ao
Joh
nso
n
Kro
pp
Han
aoka
OR
(95
% C
I)
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.