Presentation by Preet K Dhillon during the panel on 'Health Effects of Exposure to Air Pollution, as part of the CPR Initiative on Climate, Energy and Environment Clearing the Air Seminar Series. This event was organised in partnership with the Public Health Foundation of India (PHFI)

1. Air pollution and cancer
Preet K. Dhillon MPH, PhD
Centre for Environmental Health – PHFI/TISS
Centre for Chronic Conditions & Injuries (CCCI)

2. Outline
2
• Global burden of cancer
• IARC Class 1 Carcinogen
• Carcinogenic mechanisms
• AP constituents
• Evidence on cancer and air pollution
• What are the gaps we need to address?

3. Global Burden of Disease
 17.2 million cases, 8.9 million deaths
 1 in 4 lifetime risk for men, 1 in 3 for women
 2005-15: 33% increase in incidence due to:
 Population aging (16%)
 Population growth (13%)
 Changes in age-specific rates (4%)
 Leading sites:
 Prostate, TBL, colorectal men (1.6, 1.4, 0.9 million new cases)
 Breast cancer, colorectal, TBL women (2.4, .73, .64 million new
cases) JAMA Oncology 2015 Fitzmaurice C et al.
doi:10.1001/jamaoncol.2016.5688

4. Cancer deaths (no.) rankings

5. Slide courtesy of V. Cogliano (IARC)

6. IARC: Group 1 Carcinogen
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Outdoor air pollution and particulate matter: Sufficient
evidence that these are carcinogenic to humans (Oct 2013)
Benzene
Diesel exhaust
Benzopyrene
Polyclic aromatic hydrocarbons (PAHs)
Indoor emissions from coal combustion
1,3 butadieneEvidence consistent for lung cancer
Animals, humans, mechanisms
Majority of studies in Europe, USA
‘Virtually all’ - annual avg 10-30 ug/m3

7. Air pollution
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Most frequently measured pollutants
- Sulfur dioxide
- Nitrogen dioxide
- Ozone
- Carbon monoxide
- Benzene, PAH
- PM indicators – total suspended particulate, PM10, PM2.5
Air pollution mixtures
- Primary (lipid-soluble) & secondary (water-soluble)
- Atmospheric lifetime, penetration, persistence, lung
deposition

8. Carcinogenesis
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- Inhalable particles – polycyclic aromatic hydrocarbons,
volatile organic compounds, metal/compounds
- Insoluble particles deposit in thoracic & alveolar regions
- Metabolism yields products that form DNA adducts that
turn on oncogenes & turn off tumor-suppressor genes 
immune & oxidative response, DNA expression
- Trigger cascade of events lead to tumour formation
- Inflammation, cell injury/proliferation, depletion of
antioxidants, other cell defence mechanisms impaired,
reactive oxygen species -- > gene mutations
Long latency periods for studying cancer Lancet Oncology 2013 IARC Working Group

9. Global evidence
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Location
- North America (Canada, USA)
- Asia (China, Japan, Korea, India, Taiwan)
- Europe (UK, France, Italy)
- Nordic countries (Netherlands, Denmark, Sweden)
- Middle East (Iran, Saudi Arabia)
- South America (Brazil, Mexico)
- Australia
Site
- Lung, breast, leukemia, liver, brain, bladder, prostate,
ovary, colorectal, kidney, childhood

10. Reviews
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• NO2 and breast cancer (5 studies, 4 countries) a
- Pooled r suggested weak association at individual and stronger
at aggregate level (1 in Saudi Arabia)
• Outdoor AP and childhood leukemias (6 eco, 20 ca/co) b
- More than 2-fold risk (2.28) for AML and benzene
- Postnatal exposure higher estimates than pre-natal (same with
European vs. North America studies)
- Publication bias is possible; only 2 in LMICs (Taiwan)
• Traffic-related AP & childhood cancers (7 eco, 8 ca/co, ‘06) c
- No increased risk of childhood cancer (0 in LMICs)
- Sample size, methodological limits, measurement error,
publication bias (VPD, traffic-density, within 50m, NO2, benzene)
a-Keramatinia A et al. APJCP 2016; b- Fillipinni T et al. J Environ Sci Health 2015; c- Raaschou-Nielsen O. Int J C 2006

11. Longitudinal data
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• Cancer Prevention Study II (623,000 22 yrs, mortality US) a
- Kidney at 14%, bladder at 13% for 4.4 ug/m3 PM2.5
- Colon at 6% for 6.5 ppb of NO2
• Adventist Health & Smog study (597,000 for 7 yrs, US) b
- Lung adenocarcinoma 62% for each 10 ug/m3 PM2.5
- Lung cancer 43% per 10 ug/m3 PM2.5 (68% outdoors) d
• Danish nurse cohort (25,143 nurses, 15.7 yrs, Denmark) e
- No significant associations for brain cancer with NOX,
PM2.5, NO2 except doubling risk w/ PM2.5 in obese women
a-Turner MC et al. EHP 2017;b- Gharibvand L et al. Env Health 2017; c-Deng H et al. IJC 2017; d-Gharibvand et al. EHP 2017; e- Jorgensen JT et
al. Neurotoxicology 2016

12. Longitudinal data
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• Sister Study Cohort (47,591 women, 2003-09, US) a
- No association of breast cancer with AP
- 10% of ER+/PR+ associated with NO2
• California teachers study (112,378, 15.7 yrs, CA, USA) e
- Adjusted estimates, multiple breast carcinogens – no
significant associations
a-Reding KW et al. CEBP 2015; e-Garcia E et al. Environ health 2015

13. Longitudinal data
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• ESCAPE (174,770 for 17 yrs in Denmark, Austria, Italy) a
- 4 cohorts, 1985-2005
- No significant elevation in liver cancer for NO2, PM2.5
• California Cancer Registry
- 20,221 HCC (liver) patients, 9 yrs, US b
- 18%, 19% and 5% for all-cause mortality and local,
regional & distant stage for for each 5 ug/m3 PM2.5
- 352,053 patients, 1988-2009, lung cancer survival
- 30%, 4%, 26%, 38% for early stages 1 SD in NO2, O3, PM10
and PM2.5 (later stages at diagnosis - no effect)
a-Pedersen M et al. Environ Res 2017; b- Eckel SP et al. Thorax BMJ 2016

14. Case-control data
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• NO2 & UFPs and breast cancer (Montreal) a
- No significant associations
- 25% increase for every 5 ppb NO2 (383 ca/416 co) d
• Traffic-related AP & childhood leukemias (Oklahoma, US) b
- No significant associations except 5-fold increased risk
among urban kids with AML (NO2, road density, distance)
• Ambient AP & adult leukemias (1064 ca, 5039 co, Canada) b
- No significant assoc’ns, but weak effect at low NO2 levels
a-Goldberg MS et al. Environ Res 2017 ; b- Janitz AE et al. Environ Res 2016; d- Crouse DL et al. Envir Health Persp 2010

15. Case-control data
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• Indoor AP and breast cancer (New York, US) a
- 42% with synthetic log use; longer duration, older age at
exposure and genetic variants place higher risk (68%)
• Air toxics & retinoblastomas (CA Cancer Registry, 103 cases
& 30,601 controls) b
- 67% for benzene exposure during pregnancy (per IQR)
• Traffic-related AP & prostate cancer (803/969, Montreal) c
- NO2 estimates per 5 ppb ranged from 27-44% depending
on adjustment for personal, contextual factors
a-White AJ et al.l Environ Health 2014; b – Heck JE et al. J Expo Sci Environ Epidemiol 2015; c- Parent ME et al. Occup Environ Med 2013

16. Case-control data
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• Traffic-related AP and bladder cancer mortality (Taiwan) a
- Not significantly associated with petrol station density
(benzene, HC’s); controls were other GU-related deaths
• AP & bladder cancer mortality (Taiwan) b
- 37% and 98% for medium & high levels of NO2 and SO2
• Traffic-related AP & prostate cancer (803/969, Montreal) c
- NO2 estimates per 5 ppb ranged from 27-44% depending
on adjustment for personal, contextual factors
a-Ho CK et al. J Toxicol Environ Health 2010; b- Liu CC et al. Inhal Toxicol 2009

17. Ecological data
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• PM, PAHs and breast cancer variation (US)
- Significant positive associations with PAH’s (2000-12) a
- 13% for PM10 per 10 ug/m3 and 86% for PM2.5 per 5
ug/m3 (breast cancer mortality; 255,128 patients) e
- PAH & PM2.5 associated in metropolitan Atlanta c
• PM2.5 and bladder cancer mortality (13 yrs, Taiwan) b -
- Positive relationship among males in northern Taiwan
only; females in most townships
• PM2.5 & ovarian cancer mortality (13 yrs, Taiwan) a
- 20% for municipalities with 30.5-39.4 ug/m3 PM2.5
- 20% for municipalities with 39.5-51.1 ug/m3 PM2.5
a-Large C Env Sci Pollut Res 2017;b- Yeh H et al. Int J Env Res Pub Hlth 2017; c-Int J Env Health Res 2016; d- Guo Y et al. Envir Res 2016;
e-Hu H et al. Breast Cancer Res Treat 2013

18. Other
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• Ambient AP & brain cancer mortality (Can Prev Study, US) a
No association with gaseous pollutants
• Mammographic density (PM2.5 & O3)
• Proportionate Mortality (Poland, PM2.5– 14.3-52.5 ug/m3)b
- Higher attributable fractions for Lung Ca (0.2-0.4) vs.
cardiopulmonary diseases (0.13-0.3)
• Stronger associations observed for lung cancer risk &
mortality in females vs. males (no association) in Korea (27%
and 67% for > 70 ug/m3 vs. < 50 ug/m3) c
A- McKean-Cowdin R et al. CCC 2009; b- Baydyda A et al. Adv Exp Med Biol 2017; c – Hwang SS et al. J Prev med Pub Health 2007

19. Issues/gaps
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• Exposure and health outcome data often missing in LMIC’s
• Important confounders (SES, rural/urban, smoking, etc.)
• Often difficult to adjust for multiple pollutants, AP mixtures and their
interacting effects on health
• Exposures higher in LMICs but more measurement error and fewer
studies in these regions – quantifying health impact is a challenge
• For lung cancer, women and never smokers have higher risks
associated with AP – what are implications for LMICs with higher
outdoor and indoor AP levels?

20. Satellite-based NO2 levels (2005)
Changes in SO2 levels
over past decade
Global PM2.5 variation

21. PM2.5 variation over time
99% of districts above WHO annual exposure guidelines
60% above National Ambient Air Quality Standards
Source: Urbanemissions.info

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Thank you