Carcinogenicity of Outdoor Air Pollution

Centre international de Recherche sur le Cancer Lyon, France

IARC Evaluation of the

Carcinogenicity of Outdoor Air Pollution

Dana Loomis, PhD

IARC Monograph 109, Outdoor Air Pollution Lyon, 7-18 October 2013

Evaluation

•Outdoor air pollution is carcinogenic to humans (Group 1)

•Particulate matter in outdoor air pollution is carcinogenic to humans (Group 1)

Summary: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70487-X/fulltext

The IARC Monographs

(http://monographs.iarc.fr/indexfr.php)

• Evaluate factors capable of causing cancer in humans

• Environmental & occupational exposures

• Physical, chemical & biologic agents

• Lifestyle factors

• “The Encyclopedia of Carcinogens”

• More than 900 agents evaluated since 1971

• >100 carcinogenic to humans

• >300 probably or possibly carcinogenic

• National & international health agencies use the Monographs

• To identify carcinogens

• To support prevention or regulation

Evaluation in the IARC Monographs

Review of all relevant

studies Review of all relevant

studies

• Cancer in humans

• Cancer in animals

Weight of the Evidence Weight of

the Evidence

• Working Group:

discussion & debate

Final Evaluation

Final

Evaluation • Consensus

Review of Mechanisms

of Cancer

Review of Exposure

Data

Weight of the Evidence Evaluation

Cancer in humans

• Sufficient evidence

• Limited evidence

• Inadequate evidence

• Evidence suggesting lack of carcinogenicity

Cancer in animals

• Sufficient evidence

• Limited evidence

• Inadequate evidence

• Evidence suggesting lack of carcinogenicity

Mechanisms

• Strong, moderate or weak mechanistic data

• Mechanism likely to operate in humans?

Overall Evaluation

1. Carcinogenic to humans 2A. Probably carcinogenic 2B. Possibly carcinogenic

3. Not classifiable as to carcinogenicity

4. Probably not carcinogenic

Vol. 109: 24 invited experts from 11 countries

Working Group members

IARC and representatives

Source: Brauer et al. (2012). Environ Sci Technol 46:652-60

Outdoor Air Pollution is Global and Highly

Variable

Estimated PM2.5 concentrations, western Europe 2001-2006

Source: van Donkelaar et al. (2010) Environ Health Perspect 118:847–855

Sources of Principal Air Pollutants, Europe

Epidemiologic Studies

• All available studies of air pollution and cancer were reviewed (100s of studies)

• 14 studies of lung cancer were most informative

• Cohorts from the the general population in Europe, North America & Asia: millions of people and 1000s of cancer cases observed

• Quantitative exposure information

• Control of important confounders (smoking)

Lung Cancer and PM-2.5 (RR per 10µg/m ³ )

Lung Cancer and PM-10 (RR per 10µg/m ³⁾

Meta-Analysis of Lung Cancer and Particulate Matter

• Statistical analysis combining results from 14 studies in Europe, Asia & North America

• Random effects model

• Meta-RR 1,09 (1,04-1,14) per 10 µg/m ^-3 PM _2.5

• Meta-RR 1,08 (1,00-1,17) per 10 µg/m ^-3 PM ₁₀

• RR not substantially affected by gender, smoking status, or social class

(Hamra et al., EHP, 2014)

Lung Cancer and NO ₂ (RR per 10µg/m ³⁾

Lung Cancer and Indicators of Exposure to Traffic (RR)

Lung cancer and SO2 (RR per 10 µg/m ³ )

RRs for Lung Cancer and Air Pollution: Non Smokers

Heterogeneity between groups: p = 0.298 Overall (I-squared = 32.3%, p = 0.023) Burns&Swanson 1991 police

Subtotal (I-squared = 31.8%, p = 0.086) Gaertner 2004 men vehicle drivers

Coggon (1986)

Cassidy (2009)

Burns&Swanson 1991 drivers

bus

Guo 2004 SIR Iyer (1990)

Gaertner (2004)

Colt (2011)a tractor-trailer: men Silverman (1986)

Colt 2004 truck/bus/taxi men

Petersen 2010 SIR other job

Colt (2011)c light

Samanic (2008) Colt (2004)

Jensen 1987 >10 yrs bus/taxi/truck driver

Silverman (1989b) Dolin (1992)

Hoar & Hoover (1985) ID

Guo 2004 SIR

Subtotal (I-squared = 0.0%, p = 0.806) Dryson (2008)

Colt (2004)a tractor-trailer: men

Colt (2011)b heavy Dryson (2008) Brownson (1987)

Band (2005)

Colt (2011) Gaertner (2004) Risch 1988 Men

Samanic (2008)

Dryson (2008)

Pesch 2000 high exhaust exposure men

Subtotal (I-squared = 56.7%, p = 0.014)

Colt (2004)b heavy Siemiatycki (1994) truck

Cordier 1993 street vendors

Reulen 2007 motor vehicle driver

Colt (2004) Guo 2004 SIR Risch 1988 Women

Schifflers (1987)

Colt (2004)c light

taxi

Samanic (2008)

Subtotal (I-squared = 32.5%, p = 0.192) Silverman (1986)

Band (2005) Study

1.18 (1.11, 1.25) 1.00 (0.53, 1.90)

1.16 (1.07, 1.27) 1.08 (0.79, 1.48)

1.60 (1.03, 2.48)

1.43 (0.81, 2.53) 0.70 (0.49, 0.99)

1.29 (1.02, 1.63) 0.48 (0.15, 1.55)

1.23 (0.87, 1.73)

0.90 (0.61, 1.32) 1.50 (1.11, 2.02) 1.20 (0.82, 1.75)

1.60 (1.24, 2.07) 0.80 (0.52, 1.24)

1.14 (0.69, 1.89) 0.80 (0.29, 2.22) 1.29 (1.05, 1.59)

1.30 (0.51, 3.29) 1.24 (0.91, 1.69) 1.50 (0.88, 2.55) RR (95% CI)

1.01 (0.85, 1.20)

1.13 (0.96, 1.34) 0.73 (0.33, 1.61) 2.40 (1.40, 4.11)

1.30 (0.87, 1.94) 1.36 (0.47, 3.96) 1.20 (0.69, 2.08)

1.21 (0.92, 1.60)

1.10 (0.60, 2.01) 1.23 (0.87, 1.73) 1.53 (1.17, 2.00)

0.91 (0.67, 1.24)

1.69 (0.55, 5.23) 1.00 (0.78, 1.27)

1.14 (1.02, 1.27)

0.80 (0.19, 3.35) 1.20 (0.78, 1.85) 3.60 (1.15, 11.26)

0.90 (0.36, 2.25)

0.50 (0.18, 1.41) 1.06 (0.81, 1.39) 0.62 (0.24, 1.62)

2.15 (0.88, 5.27)

1.30 (0.72, 2.36)

0.75 (0.32, 1.74)

1.36 (1.16, 1.60) 1.50 (0.59, 3.82) 1.82 (0.85, 3.90)

100.00 0.83

45.93 3.38

1.77

1.05 2.83

6.35 0.25

2.88

2.27 3.80 2.39

5.21 1.77

1.33 0.33 7.90

0.39 3.51 1.21 Weight

12.01

12.20 0.55 1.18

2.13 0.30 1.13

4.44

0.94 2.88 4.73

3.50

0.27 5.77

28.86

0.17 1.82 0.26

0.40

0.31 4.57 0.37

0.42

0.96

0.48

13.01 0.39 0.59

%

1.18 (1.11, 1.25) 1.00 (0.53, 1.90)

1.16 (1.07, 1.27) 1.08 (0.79, 1.48)

1.60 (1.03, 2.48)

1.43 (0.81, 2.53) 0.70 (0.49, 0.99)

1.29 (1.02, 1.63) 0.48 (0.15, 1.55)

1.23 (0.87, 1.73)

0.90 (0.61, 1.32) 1.50 (1.11, 2.02) 1.20 (0.82, 1.75)

1.60 (1.24, 2.07) 0.80 (0.52, 1.24)

1.14 (0.69, 1.89) 0.80 (0.29, 2.22) 1.29 (1.05, 1.59)

1.30 (0.51, 3.29) 1.24 (0.91, 1.69) 1.50 (0.88, 2.55) RR (95% CI)

1.01 (0.85, 1.20)

1.13 (0.96, 1.34) 0.73 (0.33, 1.61) 2.40 (1.40, 4.11)

1.30 (0.87, 1.94) 1.36 (0.47, 3.96) 1.20 (0.69, 2.08)

1.21 (0.92, 1.60)

1.10 (0.60, 2.01) 1.23 (0.87, 1.73) 1.53 (1.17, 2.00)

0.91 (0.67, 1.24)

1.69 (0.55, 5.23) 1.00 (0.78, 1.27)

1.14 (1.02, 1.27)

0.80 (0.19, 3.35) 1.20 (0.78, 1.85) 3.60 (1.15, 11.26)

0.90 (0.36, 2.25)

0.50 (0.18, 1.41) 1.06 (0.81, 1.39) 0.62 (0.24, 1.62)

2.15 (0.88, 5.27)

1.30 (0.72, 2.36)

0.75 (0.32, 1.74)

1.36 (1.16, 1.60) 1.50 (0.59, 3.82) 1.82 (0.85, 3.90)

100.00 0.83

45.93 3.38

1.77

1.05 2.83

6.35 0.25

2.88

2.27 3.80 2.39

5.21 1.77

1.33 0.33 7.90

0.39 3.51 1.21 Weight

12.01

12.20 0.55 1.18

2.13 0.30 1.13

4.44

0.94 2.88 4.73

3.50

0.27 5.77

28.86

0.17 1.82 0.26

0.40

0.31 4.57 0.37

0.42

0.96

0.48

13.01 0.39 0.59

%

1

.2 .5 1 2 5

RR (95% CI)

Association of bladder cancer and occupational exposure

to outdoor air pollution

Epidemiologic Studies

Lung cancer risk per 5 µg/m ^-3

Summary – Human Studies

• Lung cancer is positively associated with indicators of air pollution in nearly all studies

• The associations with particulate matter are the most consistent

• Risk increases about 10% per 10 µg/m ^-3 of PM

• Associations are not explained by smoking or other confounders

• Limited evidence of an association with bladder cancer

• Inadequate data for other cancers (breast, leukemia,

childhood cancer)

Evaluation: Cancer in humans

• There is sufficient evidence in humans for the

carcinogenicity of outdoor air pollution. Outdoor air pollution causes cancer of the lung . A positive

association has been observed for cancer of the urinary bladder.

• There is sufficient evidence in humans for the

carcinogenicity of particulate matter in outdoor air

pollution. Particulate matter in outdoor air pollution

causes cancer of the lung .

Cancer in experimental animals

There is sufficient evidence in experimental animals for the carcinogenicity of:

• Organic solvent-extracted material from particles collected from outdoor air pollution

• Particulate matter in outdoor air pollution

• Solvent-extracted materials collected from outdoor air

• Diesel engine exhaust

• Outdoor air pollution

• Promotion of tumours in animals exposed to polluted outdoor air

• Updating and confirming previous IARC evaluations, including:

diesel engine exhaust, coal combustion, wood combustion

Other relevant data

• Review of 100s of studies of mechanisms of cancer in exposed humans, animals and

experimental systems.

• Strong mechanistic support: Exposures to outdoor air pollution, or particulate matter in polluted outdoor air, are associated with

increases in genetic damage that have been

shown to be predictive of cancer in humans.

Other relevant data

Key findings:

• Atmospheric mutagenic potency is quantitatively related to levels of atmospheric particulate matter

• Cytogenetic damage, DNA damage and mutations in animals, birds and plants exposed to outdoor air

pollution.

• Altered expression of genes involved in DNA damage and repair, cell cycle control, inflammation, and

oxidative stress response in people occupationally or environmentally exposed to outdoor air pollution

• Increased frequencies of chromosome aberrations and

micronuclei in exposed outdoor workers

Mutagenic potency of PM extracts and

atmospheric PM concentration in 26 countries

Cytogenic effects in humans exposed to polluted outdoor air

Loomis et al., Chin J Cancer; 2014; Vol. 33 Issue 4

www.cjcsysu.com

Importance of the Evaluation

• The evaluation of outdoor air pollution concerns the complex mixture of pollutants from all sources

• The evaluation of particulate matter includes all sizes and sources of particles, primary and secondary

• Independent data indicate 223 000 lung cancer deaths worldwide (15% of all lung cancer) are related to air pollution

• Accordingly, air pollution is responsible for more lung

cancer deaths than secondhand smoke

Ranges of Lung Cancer RR and Exposure

Concentration for Studies of PM-2.5

Conclusions

• Millions of people are exposed to air pollution at high levels, but the dimensions of the

problem are not yet fully known

• Nevertheless, classifying air pollution as a carcinogen is an important step forward

• Effective measures for reducing air pollution are available; most require collective response

• The IARC evaluation of air pollution is a call to

take action