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Traffic Air Pollution and Cancer
Annie J. Sasco, MD, Dr PH 1,2
Ann Olsson, MPH1
1 Unit of Epidemiology for Cancer PreventionInternational Agency for Research on Cancer - World Health Organization
2 Director of research, Institut National de la Santé et la Recherche Médicale
Mireille Chiron, MD & Patrice ReungoatInstitut National de Recherche sur les Transports et leur Sécurité
Lyon, France
The opinions expressed in this talk only represent those of the speaker (AJS) and should not be considered as official views of either IARC, WHO, INSERM or INRETS
Why me on this topic?
• Cancer epidemiologist – Chief of the Unit of Epidemiology for Cancer Prevention at IARC
– Deeply concerned about environmental issues
– Member of ISEE, SER, SPER, IEA, ADELF
• Having been previously involved at the European (and international) level as expert on issues such as – tobacco
– use of hormones as growth promoters in animal husbandry
– hormonal treatments (OC, HRT, tamoxifene)
– screening for cancer
But...
• Not currently working on traffic air pollution and cancer.
• Concentrating on two main domains:
– tobacco, cannabis and cancer
– breast cancer and pesticides
Measurement from the national ATMO index, built from 3 pollutant levels: Measurement from the national ATMO index, built from 3 pollutant levels: sulphur dioxide, nitrogen dioxide, ozone, without taking into account other sulphur dioxide, nitrogen dioxide, ozone, without taking into account other
important pollutants such as particulate mattersimportant pollutants such as particulate matters.
1413
8
5 54 4 4
32
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Hav
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Source: Agence de l’Environnement et de la Maîtrise de l’Energie, 1998
Expected death rate potentially avoidable by a Expected death rate potentially avoidable by a reduction of 50% of the levels of indicators for reduction of 50% of the levels of indicators for atmospheric pollution in the 9 agglomerations studied*atmospheric pollution in the 9 agglomerations studied*
0
5
10
15
20
25
30
35
Bordeaux Le Havre Lille Lyon Marseille Paris Rouen Strasbourg Toulouse
Total mortality
Cardiovascular mortality
Respiratory mortality
Annual rate for 100 000 inhabitants
* The results for Bordeaux do not take into account pollution by photo oxidant as the indicators were not available
How did I prepare for this talk?
• Usual way: Medline– not much
• Call the experts (in the French setting)
– Dr. Mireille Chiron, INRETS
– Prof. Denis Zmirou, AFSSE
• Consult important reports:– EPA: Health Assessment Document for Diesel Exhaust (2002)– HEI: Health Effects of Acute Exposure to Air Pollution (2002)– HEI: Research on Diesel Exhaust (1999)– SFSP: La pollution atmosphérique d’origine automobile et la
santé publique (1996)– IARC: IARC Monographs on the evaluation of carcinogenic risks
to humans. Volume 46. Diesel and Gasoline Engine Exhausts and Some Nitroarenes (1989)
– WHO: Transport, Environment and Health (2000)– WHO-IARC: World Cancer Report (2003)
• Rely on the IARC Monographs Programme List of IARC Evaluations
http://www-cie/monoeval/grlist.html
How did I really get into it?
• Enlisted the active participation of one of my trainees, Ann Olsson
• Went back to some historical work I did in 1979
• Drew a parallel between
smoking // air pollution and cancer from the 1930´s to post 2000
Back to history
• Early studies on air pollution and mortality/morbidity
– Firket (1931): Sur les causes des accidents survenus dans la
vallée de la Meuse, lors des brouillards de Décembre 1930
– Schenk et al. (1949): Air pollution, Donora, Pennsylvania.
Epidemiology of the unusual smog episode of October 1948
– Ministry of Health, UK (1954): Mortality and morbidity
during the London fog of December 1952
At the same time
• First major studies on tobacco and lung cancer– Wynder and Grahams (1950). Tobacco smoking as a
possible etiologic factor in bronchiogenic carcinoma
– Doll and Hill (1950). Smoking and carcinoma of the lung
– Schwartz et al. (1961). Results of a French survey on the role of tobacco, particularly inhalation, in different cancer sites
• Setting-up of prospective studies– British doctors in the UK
– American Cancer Society volunteers in the USA
Since then
• Hundreds of studies on tobacco
• Few studies on air pollution
Why such difference?
• Difficult to study validly the long term effects of air pollution
Knowledge about specific compounds
based on the IARC Monographs
on the Evaluation of
Carcinogenic Risks to Humans
Main pollutants resulting from engine exhausts
• Carbon dioxide (CO2)
• Carbon monoxide (CO)
• Nitrous oxides (NOX), in particular NO and NO2
• Particles
• Organic volatile compounds: hydrocarbons (alcanes, alcenes, aromatic monocyclic, in particular benzene and toluene), oxygenated compounds (aldehydes, acids, ketones, ethers…)
• Aromatic polycyclic hydrocarbons(benzo[a]pyrene, benzo[k]fluoranthene, benzo[b]fluoranthene, benzo[g,h,i]perylene, benz[a]anthracene
• Sulphur dioxide (SO2)
• Metals, lead in particular
Diesel and Gasoline Engine Exhausts
• Vol. 46 (1989)
• Diesel engine exhaust Group 2A (probably
carcinogenic)
• Engine exhaust, gasoline Group 2B (possibly
carcinogenic)
• Contain thousands of gaseous and particulate
substances ( 1 is individually classified in Group 1, 6 in
Group 2A and 16 in Group 2B)
Benzene
• Vol. 29 (1982) & Suppl. 7 (1987)
• Group 1 (Carcinogenic to humans)
• Increased incidence of various types of
leukemia among workers exposed to
benzene
Group 2A (probably carcinogenic to humans)
• 1,3 - Butadiene (106-99-0) Vol. 71; 1999
• Benz[a]anthracene (56-55-3) Suppl. 7 ; 1987
• Benzo[a]pyrene (50-32-8) Suppl. 7 ; 1987
• Dibenz[a,h]anthracene (53-70-3) Suppl. 7 ; 1987
• Ethylene dibromide (106-93-4) Vol. 71 ; 1999
• Formaldehyde (50-00-0) Vol. 62 ; 1995
Group 2B (possibly carcinogenic to humans)
• Acetaldehyde (75-07-0) Vol. 71 ; 1999
• Dibenz[a,h]acridine (226-36-8) Suppl. 7 ; 1987
• Dibenz[a,j]acridine (224-42-0) Suppl. 7 ; 1987
• 1,2-Dichloroethane (107-06-02) Vol. 71 ; 1999
• Lead (7439-92-1) and lead compounds, inorganic Suppl. 7 ; 1987
• 1,6-Dinitropyrene (42397-64-8) Vol. 46 ; 1989
• 1,8-Dinitropyrene (42397-65-9) Vol. 46 ; 1989
• 2-Nitrofluorene (607-57-8) Vol. 46 ; 1989• 1-Nitropyrene (5522-43-0) Vol. 46 ; 1989• Polycyclic aromatic compounds
– Benzo[b]fluoranthene (205-99-2) Suppl. 7 ; 1987– Benzo[j]fluoranthene (205-82-3) Suppl. 7 ; 1987– Benzo[k]fluoranthene (207-08-9) Suppl. 7 ; 1987– Dibenzo[a,e]pyrene (192-65-4) Suppl. 7 ; 1987– Dibenzo[a,h]pyrene (189-64-0) Suppl. 7 ; 1987– Indeno[1,2,3-cd]pyrene (193-39-5] Suppl. 7 ; 1987– 5-Methylchrysene (3697-24-3) Suppl. 7 ; 1987
Group 2B (possibly carcinogenic to humans)
Methyl tert-Butyl Ether (MTBE)
• Vol. 73 (1999) • Volatile synthetic chemical CAS no 1634-04-4
• Fuel additive in motor gasoline
• Produced in very large quantities since 1979 to replace lead as an octane enhancer
• Group 3 (not classifiable as to its carcinogenicity to
humans)
Agents or Exposures proposed for Evaluation or Re-evaluation in
future IARC Monographs
Priority
• Diesel engine exhaust (2A) High
• Gasoline engine exhaust (2B) High
• Ozone High
• Air pollution (some air pollutants) High
International Trends...• Concentrations of sulphur dioxide (SO2)and
suspended particulate matter are decreasing in developed countries, while those of Nitrogen oxides (NOX)and Ozone (O3) are either constant or increasing.
• Effective legislation
• Improved technology
• Increasing traffic
...International Trends
• In developing countries, concentrations of SO2, NOX and O3 and suspended particulate matter are raising.
• Increasing traffic and industrial emissions
• Weak legislation
• Poor technology
Pollutants of current interest
• Ground-Level Ozone the prime ingredient of smog
– cause acute respiratory problems– impair the body’s immune system
• Particulate Matter (PM) is the term used for a mixture of solid particles and liquid droplets in the air– The size varies, from a few nm to tens of µm (PM10, PM2.5)– Health concern because they easily reach the deepest recesses of
the lungs and other tissues
• Nitrogen dioxide serves (in most circumstances) as a surrogate for all traffic-related combustion products
In brief...
• Pollution of air, water and soil is estimated to account for 1-4% of all cancers (WHO-IARC, 2003)
• However, uncertainties are many,
notably because cancer takes decades to develop...
Epidemiological approaches
Comparison of morbidity/mortality between
“exposed” regions and “non-exposed” regions
Difficulties: – Adequate reference population?– Population movements?– Confounding factors?
Interpretation:– “Negative” results: Not possible to exclude increased risk– “Positive “ results: Chance?
1. Cross sectional studies
2. Case-control studies
Comparison of exposures for cases and controls
Difficulties:– Choice of pathology?– Does pertinent exposure data exist?
3. Cohort studies
An exposed population followed over time
Difficulties: – Low risk– Rare diseases– Logistic difficulties? Follow a specific population
over a long period– Comparisons?
Difficult to estimate health and ecological consequences:
– Lack of information on type and level of
current exposures
– Lack of information on past exposures
– Complex models of estimating and
predicting “uncertain risks”
Lack of power in epidemiological surveillance
• Small study sizes
• Population “at risk” not well identified
• Pertinent exposures
– Not well identified
– Multiple
– Unknown levels
Lack of power in epidemiological
surveillance• Risk level : Low
• Pathology outcome – Vague– Non specific– Rare
…difficult to interpret the results
… correct parallel:
passive smoking // air pollution
Is air pollution dangerous to health?
• The answer is: YES– Contains well documented toxic compounds
• How dangerous is it? It depends…– Characteristics of exposure
• Type
• Amount
• Distance to population
– Individual characteristics
LIFE STYLE
•Smoking
•Nutrition
•Physical Activity
Individual characteristics
OCCUPATION
•Work title
•Specific exposures
ENVIRONMENTAL
•The concentration of specific components vary greatly with locality and time
GENETIC SUCEPTIBILITY
•Heredity
Cumulative long-term effects of exposure to multiple Cumulative long-term effects of exposure to multiple compounds at varying levels remain to be evaluatedcompounds at varying levels remain to be evaluated
Occupational exposure to diesel exhaust and lung cancer risk
• 14 cohort mortality studiesfrom 1981 onwardsUK, Canada, USA, Sweden, DenmarkMostly occupational but also general cohorts
• 13 case-control studiesfrom 1984 onwardsUSA, Sweden, France, UK, Denmark, Germany. Mostly population based
• Most (but not all) studies are slightly positive, with in several evidence for a dose response relationship
Potential target cancer sites
• Lung cancer in adults
• Childhood cancers
• Other: breast, melanoma
General population exposure to air pollution
Lung Cancer• A small proportion of lung cancer is attributable to outdoor
air pollution by industrial effluent, engine exhaust products and other toxins
• Several studies have provided evidence for an increased risk of lung cancer among residents in areas with higher levels of air pollution
• Has been studied more extensively than other cancer types because of an a priori biologic hypothesis
• Other cancer types have a partly unknown etiology and therefore more research is necessary to refute or strengthen causal relationships with urban air pollution
Reference: Dockary DW et al. 1993
Type of study: Prospective cohort study, 14-16 year follow-up,8111 adults from six U.S. cities
Exposure: Fine Particles (FP) <2.5 µm, inhalable particles, SO2, O3, suspended sulphates
Results: Comparison: most/least polluted city Overall mortality: 1.26 (1.08-1.47)Lung cancer: 1.37 (0.81-2.31)
Comment: All cause mortality is increased in various models adjusting for smoking, education, BMI, occupation. Mortality
most strongly associated with FP, including sulphates
Overall mortality and lung cancer in the USA
Air pollution and lung cancer in Trieste, Italy
Reference: Biggeri A et al. 1996
Type of study: Case-control study of deceased men
755 cases, 755 controls from local autopsy registry
Exposure: Distance from sources and air particulates Results: The risk of lung cancer was highly related to city
center (p=0.0243), with an excess relative risk at zero distance of 2.2 and a smooth decrease moving away from the source (-0.015)
1.4 (1.1-1.8) for air particulates >0.298 g/m2/day
Comment: Model adjust for subject-specific confounders
Comments:
Lung cancer incidence in the USAReference: Beeson LW et al. 1998
Type of study: Prospective cohort study, followed 1977-19926338 non-smoking, non-Hispanic white adultsCalifornia, U.S.A.
Exposure: Monthly air pollution data
O3 (Interquartile range increase in 100 ppb)
PM10 (Interquartile range increase <10 µm)
SO2 (Interquartile range increase <10 µm)
Results: Men O3 RR 3.56 (1.35-9.42)
PM10 RR 5.21 (1.94-13.99) SO2 RR 2.66 (1.62-4.39)
Women PM10 RR 1.21 (0.55-2.66) (>50 µm /m3) SO2
RR 2.14 (1.36-3.37)
Comment: Sex differences partially due to differences in exposures
Lung cancer in Sweden
Reference: Nyberg F et al. 2000
Type of study: Population based case-control study
Men 40-75 years, stable residents of Stockholm county
1042 cases, 2364 population controls
Exposure: Retrospective models of estimating NOX/NO2 and SO2,
Results: 1.2 (0.8-1.6) for top NO2 decile
1.4 (1.0-2.0) (for 20 years previously)
Comment: Controlled confounding for smoking, radon, socioeconomic grouping, work in risky occupations and occupational
exposure
to diesel exhaust , other combustion products and asbestos
Overall, cardiopulmonary and lung cancer mortality in the USA
Reference: Pope CA et al. 2002
Type of study: Prospective cohort study500 000 adults among 1.2 million American Cancer
Society volunteers (CPS II)
Exposure: National data sources related to addressParticules (PM10;PM2.5), SO2, NO2,...
Results: Adjusted mortality relative risk associated with a 10 µm /m3 change in PM2.5
Overall mortality: 1.06 (1.02-1.11)Lung cancer: 1.14 (1.04-1.23)
Comment: Controlled confounding for smoking, education. marital status, BMI and alcohol consumption
Overall mortality and lung cancer in the Netherlands
Reference: Hoek G et al. 2002
Type of study: Prospective cohort study followed from 1986 to 1994
5000 adults 55-69 years
Exposure: Estimated from home address (black smoke and NO2)
Results: Overall mortality: 1.41 (0.94-2.12) for living near a major road
Lung cancer: 1.06 (0.43-2.63) for black smoke
1.25 (0.42-3.72) for NO2
Comment: Results obtained after adjustment for potential confounders
Leukemia
• Occupational exposure to benzene is associated with acute myeloid leukemia in adults
• Studies suggest an association between proximal high traffic streets and leukemia among children.
• Note: results are not unanimous
Childhood cancer in the U.S.A.Reference: Savitz DA & Feingold L 1989Type of study: Population based case-control study
Children 0-14 years, U.S.A.328 cases, 262 controls
Exposure: Traffic density of street of residence
Results: Reference: < 500 vehicles /dayAll cancers: 1.7 (1.0-2.8)
Leukaemias: 2.1 (1.1-4.0)
Brain cancer: 1.7 (0.8-3.9)
Soft tissue: 1.4 (0.5-4.4)
with dose response : All cancers Leukaemias 500-4999 v/d1.6 (0.7-3.5) 1.2 (0.4-3.9)> 5000 v/d 1.8 (0.9-3.3) 2.7 (1.3-5.9)> 10000 v/d 3.1 (1.2-8.0) 4.7 (1.6-13.5)
Comment: Adjustments for age, sex, year of diagnosis, type of residence and geographic zone do not change results
Childhood cancer in Sweden
Reference: Feychting M et al. 1998
Type of study: Case-control study nested in a population of children having lived for at least a year within 300m of 220 and 440k lines in Sweden during 1960-1985
142 cases, 568 controls
Exposure: Estimated NO2 concentration based on home address
Results: All cancers Leukaemia CNS<39µm/m3 1 1 140-49 1.3 (0.4-4.3) 1.7 (0.2-14.6) 1.0 (0.1-12.7)>50 2.7 (0.9-8.5) 2.7 (0.3-20.6) 5.1 (0.4-61.2)
Comment: Adjustments are made for EMF and confounders
Childhood leukaemia in the UKReference: Harrisson RM et al. 1999
Type of study: Case control and incidence ratio study West Midlands, UK
Children 0-15 years old with leukemia (130 cases) or solid tumors (251 controls) diagnosed between 1990-
1994
Exposure: Distance of home from main road and petrol stationcase-control IR
Results: analysis analysis< 100 m main road 1.61 (0.90-2.87) 1.16 (0.74-1.72)
< 100 m petrol station 1.99 (0.73-5.43) 1.48 (0.65-2.93) both 5.91 (0.61-57.3) 0.81 (0.16-2.38)
Comment: Adjustments are made for age and sex
Leukaemia and childhood cancer in the U.S.A.
Reference: Pearson RL et al. 2000
Type of study: Case-control study
Children 0-14 years living in Denver, U.S.A.
320 cases, 259 controls
Exposure: Weighted traffic density at home address
Results: All cancers 5.90 (1.69-20.56)
Leukemia 8.28 (2.09-32.80)
( for > 20000 vehicles/day)
Childhood cancer in DenmarkReference: Raaschou-Nielsen O et al. 2001
Type of study: Case-control study
Children from the Danish Cancer Registry diagnosed with cancer (leukemia, tumor of the central nervous system, or malignant lymphoma) before 15 years of age between 1968-1991
1989 cases, 5506 population controls
Exposure: Advanced model of estimated NO2 and benzene
exposure from traffic intensity in utero and during childhood
Results:Results: All cancersAll cancers Leukaemias CNS Leukaemias CNS LymphomasLymphomas
Pregnancy500-4999 veh/d 1.0 (0.9-1.1) 0.9 (0.8-1.0) 1.0 (0.9-1.2) 1.0 (0.8-1.4)
5000-99990.9 (0.7-1.2) 0.8 (0.6-1.2) 0.7 (0.5-1.2) 1.7 (1.0-2.8)
>10000 0.7 (0.5-1.1) 0.8 (0.5-1.3) 0.6 (0.3-1.1) 1.2 (0.5-3.0)
Childhood500-4999 veh/d 0.9 (0.8-1.0) 0.9 (0.8-1.1) 0.9 (0.7-1.0) 0.9 (0.7-1.2)
5000-99990.8 (0.6-1.1) 0.8 (0.5-1.2) 0.6 (0.4-1.1) 1.5 (0.8-3.0)
>10000 1.0 (0.7-1.6) 1.1 (0.6-2.2) 0.9 (0.4-1.8) 1.3 (0.4-4.8)
Hodgkin’s diseaseHodgkin’s disease
Benzene NO2
0.5-1.2* 1.7 (0.8-3.8) 1.5-2.9* 1.5 (0.7-3.2)
>1.3* 4.3 (1.5-12.4) >3.0* 6.7 (1.7-26.0)*in 1000 ppb - days
Breast cancer in the U.S.A.Reference: Lewis-Michl EL et al. 1996
Type of study: Case-control studyWomen 20-79 years old, Nassau and Suffolk
counties, Long Island, U.S.A.1420 cases, 1420 controls (derived from NY
driving license registry)
Exposure: Residential proximity to industrial facilities and traffic
Results: High traffic intensity and post menopausal breast cancerNassau Suffolk
Adjusted OR 1.29 (0.77-2.15) 0.89 (0.40-1.99)
Comment: Adjustments are made for age, occupation, education
Melanoma
• Chloroflourocarbons cause destruction of the ozone layer and enhance the risk of skin cancer through increased ultraviolet radiation
For increased power in epidemiological surveillance...
• Epidemiology– Identification of compounds and “true” exposure levels – Identification of “exposed” people– Precise choice of pathology – Test dose-response relationships – Biological markers of exposure and effects
• …for surveillance • …for epidemiology
• Prevention– Exposure surveillance – Intervention
Conclusion
Overall, there is an association between lung cancer in adults and some childhood tumours and air pollution, including but not limited to the one coming from traffic.
Even if the relative risk is of limited magnitude, the extent of the population exposed is large and therefore prevention is warranted.