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Full text of "World Trade Center STAC Meeting Presentation - Cancer"

Petition on Cancer, Epidemiology 
and Overview of Mechanisms of 

Carcinogenesis 



Elizabeth Ward, PhD 



Request from Dr. Howard 

"I request that the STAC review the available 
information on cancer outcomes associated with 
exposures resulting from the September 11, 
2001 terrorist attacks, and provide advice on 
whether to add cancer, or a certain type of 
cancer, to the List (of WTC related health 
conditions) specified in the Zadroga Act." 



It is that exposure to WTC 

dust may cause cancer 

a) unlikely 

b) possible 

c) biologically plausible 

d) probable 

e) proven 



What is the scientific rationale? 



Scientific rationale 



What we know 
What don't we know 
What we believe 



Review of Data 



(1) Epidemiologic studies 

(2) Potential carcinogens present in WTC dust 

(3) Mechanisms of carcinogenesis 



Epidemiologic Cohorts 

(adopted from Perlman et al., 2011) 



Name or sponsor 


Groups Studied 


Size 
(12/31/2010) 


Notes 


Fire Department of 
New York 


Firefighters and 
EMS Workers 


15,415 


Employer-based 
medical program 


NY & NJ WTC 
Clinical Consortium 


Law enforcement & 
other responders, 
sanitation & construction 
workers, volunteers 


29,572 


Provides screening, 
monitoring and 
treatment 


WTC Environmental 
Health Center 


Area workers, residents, 
students 


5,130 ^^H 


Monitors & treats, 
includes children 


WTC Health 
Registry 


Rescue & recovery 
workers, area workers, 
residents, students 


71,437 


30% recruited from 
employers & govt, 
agencies, others 
self-enrolled 



FDNY Study 

9,853 firefighters employed on 1/1/1996; 
8,927 WTC-exposed starting on 9/11/2001 

Standardized incidence ratio for all cancers 
among WTC-exposed firefighters of 1.10 
based on general population rates and 1.19- 
1.32 based on unexposed firefighters 

Elevated or borderline excesses for stomach, 
colon, melanoma, prostate, thyroid, NHL 
compared to general population rates 



Other epidemiologic findings 
related to cancer 

No excess of all cancers combined or 8 major 
organ systems in first follow-up of WTC Health 
Registry Cohort 

Case reports suggesting possible excess of 
multiple myeloma 



Limitations of Epidemiologic Evidence 

- Misclassification -^ difficult to accurately 
estimate exposure ^ reduced strength of 
association ^ lack of clear "exposure- 
response" trend 

- Complex and multiple exposures -^ 

difficult to attribute causality ^ lack of 
consistency in findings among exposed 
populations & studies 

- Population sizes ■» insufficient to rule 
out small risks and risks for rarer cancers 



Limitations of Epidemiologic Evidence, 

cont. 

Cancer's latent period ^ cancer risk may not 
appear until 20 or more years after first 
exposure. 



Latent period is most relevant in epidemiologic 
studies when results are negative and follow- 
up period may be too short to observe an 
effect. 



10 



If epidemiologic data are not definitive, 
what can we learn from exposure data? 

Interpreting air sampling data from WTC site is 
difficult and controversial; no data in the critical 
first week after the building collapse 

(Belief) Relatively low air levels measured in some 
early studies at the WTC site inconsistent with 
observed high rates of respiratory symptoms 

One approach to evaluating potential cancer 
hazard is to examine composition of the initial 
dust/smoke (as reflected in the dust samples 
collected) 



11 



Who could have been or could be exposed to the 
materials present in the initial dust/smoke?* 

Initial collapse of the WTC 

• Local and downwind residents 

• Rescue workers 

• Commuters 

• Shop/business owners, operators & customers 

Re-suspension of the dust/smoke during the following week 

• Professional & volunteer rescue workers 

• Outdoor & indoor cleanup workers 

• Residents & workers in Wall Street area downwind 

Re-suspension of dust/smoke during the next weeks/months 

• Workers not wearing respiratory protection at WTC site 

• Indoor cleanup workers not wearing respiratory protection 

• Residents & workers returning to poorly cleaned buildings 

* Although not measured, gases would be associated with many of these exposures 
Adapted from Lioy, 2006 



12 



What materials were present in the 

initial dust/smoke? 



Gypsum (major component of drywa 

Concrete dust (cement dust, crystalline silica) 

Glass fragments and man-made vitreous fibers 

Asbestos 

Polycyclic aromatic hydrocarbons (PAH's) 

Metals (hexavalent chromium, nickel, arsenic) 

Volatile organic compounds (benzene) 



13 



Which materials appear to be of most 

concern for cancer? 



Gypsum (major component of drywa 

Concrete dust (cement dust, crystalline silica) 

Glass fragments and man-made vitreous fibers 

Asbestos 

Polycyclic aromatic hydrocarbons (some PAH's) 

Metals (hexavalent chromium, nickel, arsenic) 

Volatile organic compounds (benzene) 



RED = IARC Group 1, NTP human carcinogen 



14 



Understanding Cancer and Related Topics 

Understanding Cancer 



Developed by: 

Lewis J. Kleinsmith, Ph.D. 

Donna Kerrigan, M.S. 

Jeanne Kelly 

Brian Hollen 

Discusses and illustrates what cancer is, 
explains the link between genes and 
cancer, and discusses what is known 
about the causes, detection, and 
diagnosis of the disease. 



Artwork by Jeanne Kelly. © 2004. 



These PowerPoint slides are not locked files. You can mix and match slides from different tutorials as 
you prepare your own lectures. In the Notes section, you will find explanations of the graphics. 

The art in this tutorial is copyrighted and may not be reused for commercial gain. 

Please do not remove the NCI logo or the copyright mark from any slide. 

These tutorials may be copied only if they are distributed free of charge for educational purposes. 



J 



Loss of Normal Growth Control 



Normal 
cell division 



Q 






/ \ 

I 1 



Cell damage — 
no repair 



Cell Suicide or Apoptosis 



cell division 





ffft 








*l 



First Second 

mutation mutation 






r i^5! 






#»?£■ 



Third Fourth or 

mutation later mutation 



Uncontrolled growth 



icroscopic Appearance of Cancer Cells 



Normal Cancer 





O 




® © 

5) (5 



a 



a 




o 




Large, variably shaped nuc. 



Small cytoplasmic volume 
relative to nuclei 



Variation in cell size and sha 



Loss of normal specialized 
cell features 



J 



Lag Time 



Cigarettes 
Smoked 

per Person 
per Year 



20-Year Lag Time Between 
Smoking and Lung Cancer 



4000 



3000 



2000 



1000 



Cigarette 

consumption 

(men) 



Lung 

cancer 

(men) 




Lung Cancer 
100 Deaths (per 

100,000 people) 



1900 1920 1940 1960 1980 

Year 



J 



Genes and Cancer 



^ 




Chromosomes 
are DNA 
molecules 



IMwMHriil 



J 



Oncogenes 



Normal cell 



^ 
& 




Normal 
genes 
regulate 
cell growth 



^ 



Cancer cell 




Oncogenes 
accelerate 
cell growth 
and division 



Mutated/damaged oncogene 



Tumor Suppressor Genes 



Normal cell 






Remove or inactivate 
tumor suppressor genes 



■^v 



Cancer cell 



# 





Damage to 
both genes 
V leads to 



cancer 



Mutated/inactivated 
tumor suppressor genes 



J 



DNA Repair Genes 




Normal DNA repair 



mismatch 



cancer 




Cancer 



AGi iTG AG1A1TG 

No DNA repair 



Cancer Tends to Involve Multiple Mutations 



Benign tumor cells 
grow only locally and 
cannot spread by 
invasion or metastasis 



Malignant cells invade 
neighboring tissues, enter 
blood vessels, and 
metastasize to different sites 



Time i 

Mutation Cells Mutations 

inactivates proliferate inactivate 
suppressor DNA repair 

gene genes 



s 




^ 






:m***M\ 


w 


^^^^^^f^^m 



Proto-oncogenes 
mutate to 
oncogenes 



More mutations, 
more genetic 
instability, 
metastatic 
disease 



MlWWill 



Process of Carcinogenesis 



Many cancers take a 
long time to develop 



Most tumors evolve through a 
number of stages 




Time 



Initiation Promotion 



Malignant 
transformation 



Progression, invasion and 
metastasis 



25 



Inflammation and Cancer 

Inflammation is a normal response to tissue damage 
resulting from infection, chemical irritation and/or 
wounding. When it becomes chronic, it can damage 
the body and lead to illness. 

Inflammatory diseases associated with cancer include 
certain immunologic disorders, infections and chronic 
chemical and mechanical irritation. 



Inflammation can lead to cancer through a variety of 
mechanisms: increased cell proliferation, generating 
mutagens from releasing reactive oxygen and nitrogen 
species, and producing biologically active chemicals 
that influence the cellular/tissue microenvironment. 



26 



Other considerations 

Duration of exposure: Since inhaled fibers and 
dusts may remain in the body for a long time, a 
short-term environmental exposure can lead to a 
long-term biological exposure 

Latent period: Although on average it takes 20 or 
more years for a solid tumor to develop after, 
most carcinogens can act at during multiple 
stages of the carcinogenic process, and can 
impact cancer risk in a shorter time frame; this is 
most evident when an exposure is withdrawn. 



27 



J 



Lag Time 



Cigarettes 
Smoked 

per Person 
per Year 



20- Year Lag Time Between 
Smoking and Lung Cancer 



4000 



3000 



2000 



1000 



Cigarette 

consumption 

(men) 



Lung 

cancer 

(men) 




Lung Cancer 
100 Deaths (per 

100,000 people) 



1900 1920 1940 1960 1980 

Year 



Relative risk of lung cancer falls rapidly after smoking 

cessation 



25 1 



-•-Male Female 




Time since cessation (years) 



Source: Oza S, et al. Preventive Medicine (2011). 



29 



Incidence rates* of invasive and in-situ female breast cancer by age, adjusted for delayed reporting, 

US, 1975-2007 



450 



400 



350 - 



300 

o 
o 
o 

§ 250 



CD 

S" 200 

cc 



150 



100 



50 



Invasive 




Ages 50+ 



Ages < 50 



1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

1975 1979 1983 1987 1991 1995 1999 2003 2007 



450 



400 



350 



300 



250 



200 



150 



100 



In-situ 



Ages 50+ 




Ages < 50 



1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 

1975 1979 1983 1987 1991 1995 1999 2003 2007 



*Rates are per 100,000, age-adjusted to the US standard population. 

Data Source: Surveillance, Epidemiology, and End Results (SEER) Program, SEER 9 registries, National Cancer Institute. 



30 



Moving on 



Asbestos 
PAH's 

Particulates 
Metals and VOC's 



31 



Concrete dust 

Concrete is a mixture of Portland cement, sand, 
gravel and water 



Pulverized concrete contains crystalline silica and 
cement dust, including Portlandite (Ca(OH) 2 ) 
which is highly caustic 

Crystalline silica causes lung cancer in humans 
(IARC); most common health effect is lung 
disease (silicosis); also associated with renal 
disease, scleroderma, rheumatoid arthritis 



32 



Cement dust 

Most (but not all) studies of respiratory health among cement 
manufacturing workers have found increased symptoms 
(cough, phlegm and dyspnea) and reduced lung function 
(FEV^FVC and FEV^FVC ratio) 

One study found increased prevalence of ulcer-like and reflux- 
like dyspepsia among cement workers vs. unexposed controls 
and high- vs. low-exposed cement workers 

Cohort and case-control studies have suggested associations 
between cement-exposed occupations and cancer of the lung, 
stomach, colon and head & neck, including pharynx and 
larynx 

33 



Carcinogenicity of cement dust 



• Has not been reviewed by IARC or NTP 

• Although the UK Health and Safety Executive (2006) did not 
find that epidemiologic evidence was convincing of a causal 
association between cement dust exposure and cancer, 
they noted that: 

"As a highly alkaline substance, cement can cause irritation at sites of 
contact, such as the mouth, throat and lungs. Persistent chronic 
irritation will cause repeated cycles of cell death, cell proliferation and 
other inflammatory responses. It is recognized that this process can be 
a step on the pathway to cancer. Thus it is biologically plausible that 
cement dust could have the potential to cause cancers at sites of 
contact/' 



34 



Preview 



After the 4 presentations and discussion 
(before the public comment period that will 
begin at 3:45 pm) we will poll the committee 



35 



It is that exposure to 

WTC dust may cause cancer. 

a) unlikely 

b) possible 

c) biologically plausible 

d) probable 

e) proven 



36 



WTC STAC Committee 




UNLK 



POSs 



B.P. 



PROB 



PROV 



Range of Opinion 



37 



Framing tomorrow's discussion 

• Identify critical evidence not presented 

• Discussion of opposing positions...? 

• Discussion of scientific rationale...? 

• Discussion of cancer sites... 



Cautions and perspectives 
Draft letter of response 



38