Traffic Air Pollution and Cancer

1
Traffic Air Pollution and Cancer

• Annie J. Sasco, MD, Dr PH 1,2
• Ann Olsson, MPH1
• 1 Unit of Epidemiology for Cancer Prevention
• International 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 Reungoat
• Institut 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

2
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

3
But...

• Not currently working on traffic air pollution
  and cancer.
• Concentrating on two main domains
• tobacco, cannabis and cancer
• breast cancer and pesticides

4
Measurement from the national ATMO index, built
from 3 pollutant levels sulphur dioxide,
nitrogen dioxide, ozone, without taking into
account other important pollutants such as
particulate matters.
Source Agence de lEnvironnement et de la
Maîtrise de lEnergie, 1998
5
Expected death rate potentially avoidable by a
reduction of 50 of the levels of indicators for
atmospheric pollution in the 9 agglomerations
studied
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
6
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

7

• 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 dorigine
  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

8
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 1930s to post 2000

9
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

10
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

11
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

12
Knowledge about specific compounds

• based on the IARC Monographs
• on the Evaluation of
• Carcinogenic Risks to Humans

13
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(benzoapyrene,
  benzokfluoranthene, benzobfluoranthene,
  benzog,h,iperylene, benzaanthracene
• Sulphur dioxide (SO2)
• Metals, lead in particular

14
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)

15
Benzene

• Vol. 29 (1982) Suppl. 7 (1987)
• Group 1 (Carcinogenic to humans)
• Increased incidence of various types of leukemia
  among workers exposed to benzene

16
Group 2A (probably carcinogenic to humans)

• 1,3 - Butadiene (106-99-0) Vol. 71 1999
• Benzaanthracene (56-55-3) Suppl. 7 1987
• Benzoapyrene (50-32-8) Suppl. 7 1987
• Dibenza,hanthracene (53-70-3) Suppl. 7 1987
• Ethylene dibromide (106-93-4) Vol. 71 1999
• Formaldehyde (50-00-0) Vol. 62 1995

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Group 2B (possibly carcinogenic to humans)

• Acetaldehyde (75-07-0) Vol. 71 1999
• Dibenza,hacridine (226-36-8) Suppl. 7 1987
• Dibenza,jacridine (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

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Group 2B (possibly carcinogenic to humans)

• 2-Nitrofluorene (607-57-8) Vol. 46 1989
• 1-Nitropyrene (5522-43-0) Vol. 46 1989
• Polycyclic aromatic compounds
• Benzobfluoranthene (205-99-2) Suppl. 7 1987
• Benzojfluoranthene (205-82-3) Suppl. 7 1987
• Benzokfluoranthene (207-08-9) Suppl. 7 1987
• Dibenzoa,epyrene (192-65-4) Suppl. 7 1987
• Dibenzoa,hpyrene (189-64-0) Suppl. 7 1987
• Indeno1,2,3-cdpyrene (193-39-5 Suppl. 7 1987
• 5-Methylchrysene (3697-24-3) Suppl. 7 1987

19
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)

20
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

21
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

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...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

23
Pollutants of current interest

• Ground-Level Ozone the prime ingredient of smog
• cause acute respiratory problems
• impair the bodys 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

24
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...

25
Epidemiological approaches
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1. Cross sectional studies

• 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?

27
2. Case-control studies

• Comparison of exposures for cases and controls
• Difficulties
• Choice of pathology?
• Does pertinent exposure data exist?

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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?

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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

30
Lack of power in epidemiological surveillance

• Small study sizes
• Population at risk not well identified
• Pertinent exposures
• Not well identified
• Multiple
• Unknown levels

31
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

32
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

33
Individual characteristics

• LIFE STYLE
• Smoking
• Nutrition
• Physical Activity

• GENETIC SUCEPTIBILITY
• Heredity

• ENVIRONMENTAL
• The concentration of specific components vary
  greatly with locality and time

• OCCUPATION
• Work title
• Specific exposures

Cumulative long-term effects of exposure to
multiple compounds at varying levels remain to be
evaluated
34
Occupational exposure to diesel exhaust and lung
cancer risk

• 14 cohort mortality studies
• from 1981 onwards
• UK, Canada, USA, Sweden, Denmark
• Mostly occupational but also general cohorts
• 13 case-control studies
• from 1984 onwards
• USA, 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

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General population exposure to air pollution

• Potential target cancer sites
• Lung cancer in adults
• Childhood cancers
• Other breast, melanoma

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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

39
Overall mortality and lung cancer in the USA

• 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) lt2.5 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

40
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 (p0.0243), 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 gt0.298
  g/m2/day
• Comment Model adjust for subject-specific
  confounders
• Comments

41
Lung cancer incidence in the USA

• Reference Beeson LW et al. 1998
• Type of study Prospective cohort study,
  followed 1977-1992
• 6338 non-smoking, non-Hispanic white adults
• California, U.S.A.
• Exposure Monthly air pollution data
• O3 (Interquartile range increase in 100 ppb)
• PM10 (Interquartile range increase lt10 µm)
• SO2 (Interquartile range increase lt10 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) (gt50 µm
  /m3) SO2 RR 2.14 (1.36-3.37)
• Comment Sex differences partially due to
  differences in exposures

42
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

43
Overall, cardiopulmonary and lung cancer
mortality in the USA

• Reference Pope CA et al. 2002
• Type of study Prospective cohort study
• 500 000 adults among 1.2 million American
  Cancer Society volunteers (CPS II)
• Exposure National data sources related to
  address
• Particules (PM10PM2.5), 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

44
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

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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

46
Childhood cancer in the U.S.A.

• Reference Savitz DA Feingold L 1989
• Type 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 lt 500 vehicles /day
• All 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/d 1.6 (0.7-3.5) 1.2 (0.4-3.9)
• gt 5000 v/d 1.8 (0.9-3.3) 2.7 (1.3-5.9)
• gt 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

47
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 300 m 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
• lt39µm/m3 1 1 1
• 40-49 1.3 (0.4-4.3) 1.7 (0.2-14.6) 1.0
  (0.1-12.7)
• gt50 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

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Childhood leukaemia in the UK

• Reference 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 station
• case-control IR
• Results analysis analysis
• lt 100 m main road 1.61 (0.90-2.87) 1.16
  (0.74-1.72) lt 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

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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 gt 20000 vehicles/day)

50
Childhood cancer in Denmark

• Reference 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

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• Results All cancers Leukaemias
  CNS Lymphomas
• Pregnancy
• 500-4999 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)
• 5000-9999 0.9 (0.7-1.2) 0.8 (0.6-1.2)
  0.7 (0.5-1.2) 1.7 (1.0-2.8)
• gt10000 0.7 (0.5-1.1) 0.8 (0.5-1.3)
  0.6 (0.3-1.1) 1.2 (0.5-3.0)
• Childhood
• 500-4999 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)
• 5000-9999 0.8 (0.6-1.1) 0.8 (0.5-1.2)
  0.6 (0.4-1.1) 1.5 (0.8-3.0)
• gt10000 1.0 (0.7-1.6) 1.1 (0.6-2.2)
  0.9 (0.4-1.8) 1.3 (0.4-4.8)
• Hodgkins disease
• Benzene NO2
• 0.5-1.2 1.7 (0.8-3.8) 1.5-2.9 1.5 (0.7-3.2)
• gt1.3 4.3 (1.5-12.4) gt3.0 6.7 (1.7-26.0)
• in 1000 ppb - days

52
Breast cancer in the U.S.A.

• Reference Lewis-Michl EL et al. 1996
• Type of study Case-control study
• Women 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 cancer
• Nassau Suffolk
• Adjusted OR 1.29 (0.77-2.15) 0.89 (0.40-1.99)
• Comment Adjustments are made for
  age, occupation, education

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Melanoma

• Chloroflourocarbons cause destruction of the
  ozone layer and enhance the risk of skin cancer
  through increased ultraviolet radiation

54
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

55
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.