Lung cancer and mesothelioma are commonly caused by occupational and para-occupational asbestos exposure. Asbestos fibers are carcinogenic and can lead to lung cancer and mesothelioma even with low-level or brief exposures. While smoking increases the risk of lung cancer synergistically when combined with asbestos exposure, asbestos alone causes mesothelioma regardless of smoking status. Both malignant and non-malignant asbestos-related diseases have long latency periods of typically 20-30 years.

1. Lung cancer and mesothelioma due to occupational
and para-occupational asbestos exposure
Dr. MALAY SARKAR
Indira Gandhi Medical College, Shimla

2. Asbestos
 About 125 million people in the world are exposed to
asbestos at the workplace.
 All forms are carcinogenic
 Asbestos: leading cause of occupationally-related cancer
death (~50%)
 Second most fatal manufactured carcinogen (after
tobacco).
 Fibers: long and thin fibers (>5 μm long, <3 μm wide, with
aspect ratio (length to width) ≥3:1)
Rushton L, et al. Occup Environ Med. 2008;65(12):789-800.
WHO Asbestos: elimination of asbestos-related diseases 2018

3. Arthur L Frank and TK Joshi. Annals of Global Health 2014;80:257-262

4. Morphological classification: asbestos fibers
Serpentine group:
Curly fibers
Amphibole group
Straight fibers
Chrysotile (white asbestos)
1. Amosite (brown asbestos),
2. Crocidolite (blue asbestos)
3. Anthophyllite (yellow asbestos)
4. Actinolite,
5. Tremolite
90% to 95% of asbestos used
worldwide.
Tweedale G: Nat Rev Cancer 2002;2(4):311-315

5. Amphibole fibers are all straight
and needle-like in their microscopic
appearance.
Chrysotile asbestos: Serpentine
fibers appear wavy under low
magnification
Arthur L Frank and TK Joshi. Annals of Global Health 2014;80:257-262

6. Asbestos-related lung diseases
Non-malignant:
Asbestosis
Benign asbestotic pleural effusion
Malignant:
Lung cancer
Mesothelioma (pleural, peritoneal, pericardial and testicular)
GIT cancer (esophagus, stomach and colo-rectal)
Oropharynx
Larynx
Renal and ovary
Lancet Oncol. 2009 May; 10(5):453-4.

7. Lynch KM, Smith WA. Pulmonary asbestosis: carcinoma of the
lung in asbestos-silicosis. Am J Cancer 1935; 24: 56.
Gloyne SR. Two cases of squamous carcinoma of the lung
occurring in asbestosis. Tubercle 1935; 17: 5.

8. Globally, approximately 75% of lung cancer cases are attributable
in part to smoking Tobacco
Field et al. Clin Chest Med 2012;33:681–703
Doll and Peto estimated that occupational exposures are
responsible for 15% and 5% of lung cancer in men and women,
respectively, in the United States
Doll R, Peto R. J Natl Cancer Inst 1981;66:1191–308.

9. Asbestos-related lung cancer
 No specific clinical features
 No predilection for any specific location or histologic types
 Smoking and asbestos: multiplicative or sub-multiplicative
effect
 Persistence of the risk after cessation of exposure
 Long latency period of 20-30 years
 Linear dose-response relationship
 Threshold dose??
Arch Environ Occup Health 2014;69(4):191-206.
Nat Rev Cancer2002 Apr;2(4):311-5.

10. 1. Mesothelioma: 85–90% caused by asbestos exposure
2. Latent period: usually 30-40 years and a minimum of 10
years
3. Any occupational history of brief or low-level exposure
should be considered sufficient for mesothelioma to be
designated as occupationally related
4. Smoking has no influence on the risk of mesothelioma
Asbestos and malignant mesothelioma
Roggli VL et al. Mesothelioma. In: Roggli VL, Greenberg SD,Pratt PC, ed. Pathology of
asbestos associated diseases. Boston: Little Brown and Co,1992:109-64.

11. Smoking, asbestos and lung cancer:
additive or multiplicative??

12. Multiplicative effects
Asbestos exposure only: 5-fold risk
Smoking alone: 10-fold risk
Smokers with Asbestos exposure :
50-fold above that for unexposed
Asbestos exposure, smoking and lung cancer
Selikoff et al.JAMA 1968 Apr 8;204(2):106-12.
0 20 40 60
Chronic smoking
Asbestos
Combined
Lung cancer risk: synergism
between smoking and Asbestos
exposure
Series1

13. Group Death rate (Rate per 100,000
man-years standardized for
age)
Mortality ratio
Asbestos(-), Smoker (-) 11.3 1.0
Asbestos (+), Smoker(-) 58.4 5.2
Asbestos(-), Smoker(+) 122.6 10.9
Asbestos (+), Smoker(+) 601.6 53.2
Hammond EC, et al. Asbestos exposure, cigarette smoking and death rates. Ann N
Y Acad Sci. 1979;330:473-90.

14. Fibers Biopersistence and
pathogenicity

15. Biopersistence: important factor dictating pathogenicity of a fiber
Donaldson K, et al. Toxicol Sci 2006, 92:5-22.

16. Is chrysotile fibers hazardous?

17. Chrysotile fibers break apart from fiber bundles and
multiply once within the lung, while the amphiboles do
not. This means a higher rate of chrysotile in the lungs and
a higher rate of translocation from the lungs to pleura
Statement of Dr. RA Lemen on NIOSH asbestos roadmap 2007

18. Bellman B, et al. Ann. Occup. Hyg. 1987; 31(4B), 693-709.

19. Results of fibre analyses at surgery (first
tissue excision) and autopsy (second tissue
excision) in relation to time from 10
patients.
Pulmonary asbestos fibre burden was stable between both examinations. Electron
microscopy demonstrated: predominant chrysotile (median 80%).
Feder et al. Eur Respir J 2017; 49: 1602534

20. Type of asbestos Carcinoma Mesothelioma
Amosite 11 1
Anthophyllite 16 2
Crocidolite 16 4
Canadian chrysotile 17 4
Rhodesian
chrysotile
30 0
Controls 0 0
Br. J. Cancer 1974;29:252

21. Loomis et al. Occup Environ Med 2009;66:535–542.
Follow-up of 5770 workers working between 1950 and 1973 in
any of four plants in North Carolina, USA
Conclusion:
“Exposure to Chrysotile asbestos in textile manufacturing is
associated with increased risk of lung cancer, asbestosis
and Mesothelioma”

22. All fibers are pathogenic to human
All forms of asbestos (IARC Group 1), including
chrysotile, are causally associated with an increased
risk of cancer of the lung, larynx, and ovary;
mesothelioma; and asbestosis.
World Health Organization. Chrysotile Asbestos. Geneva, Switzerland:
WHO. 2014.
Collegium Ramazzini :Ann Glob Health. 2016 Jan-Feb;82(1):209-13.

23. Stanton hypothesis:
“Long (≥8 mm in length) and thin (≤0.25 mm in
width) asbestos fibers are strongly carcinogenic”
But
shorter and thicker fibers pose less risk
Stanton MF et al. JNCI 1981;67:965–975

25. Are short fibers hazardous?

26. Suzuki et al. Industrial Health 2001, 39, 150–160
Asbestos fibers in the lung and mesothelial tissues (mesotheliomatous tissue
and hyaline plaque) taken from 151 human malignant mesothelioma cases were
identified and characterized by high resolution analytical electron microscopy.
Lung tissues: Chrysotile with
amphiboles: 39.1%
Amphiboles: 35.2% Chrysotile: 25.7%
Mesothelial tissues: Chrysotile: 77.2% Chrysotile plus
amphibole: 20.8%
Amphibole: 2.0%

27. Suzuki et al. Industrial Health 2001, 39, 150–160
The majority (81.4%) of asbestos fibers detected in the lung
and mesothelial tissues were shorter than 5 μm in length.

28. Int J Hyg Environ Health. 2005;208(3):201-10.
Long, thin asbestos fibers: only 2.3% of total fibers
Fibers ≤ 5 mm in length: 89.4%
Fibers ≤ 0.25 mm in width: 92.7%
Chrysotile was the most common asbestos type to be categorized as short,
thin asbestos fibers.
Conclusion:
Contrary to the Stanton hypothesis, short, thin, asbestos fibers appear to
contribute to the causation of human malignant mesothelioma. These
findings suggest that it is not prudent to take the position that short
asbestos fibers convey little risk of disease.

29. Stanton and Wrench. J Nat Cancer Inst 1972; 48: 797-821
Animal experiment:
Amosite, chrysotile, and crocidolite yielded equally high
incidences of pleural mesothelioma in the range of 58-75%.

30. Loomis et al. Occup Environ Med 2010;67:580-584

31. Dodson et al. Am J Ind Med. 2003 Sep;44(3):291-7.
Reviewed animal and human literature related to the fiber
length
Conclusions:
Asbestos fibers of all lengths induce pathological responses and
that caution should be exerted when attempting to exclude any
population of inhaled fibers, based on their length, from being
contributors to the potential for development of asbestos-
related diseases.

32. There is no safe limit to any asbestos: anything
above background can cause cancer in human

33. Exposure Rats Carcinoma Mesothelioma
1 day 219 3 2
3 months 180 8 1
6 months 90 7 0
12 months 129 35 6
24 months 95 37 2
Controls 126 0 0
Br. J. Cancer 1974;29:252
• Duration of exposure and cancer

34. Cumulative
exposure (fiber
years)
125 Cases 125 Controls Odds ratio 95%-CI
Not exposed 11 67 1
>0-0.15 14 12
7.9 2.1-30
>0.15-1.5 38 25 21.9 5.7-83.8
>1.5-15 46 16 47.1 11.5-193
>15 16 5 45.4 8.1-257
Rödelsperger et al. Am J Ind Med. 2001 Mar;39(3):262-75.

35. Fourteen case–control studies on lung cancer from Europe and Canada were
pooled in the SYNERGY project
Olson et al. Epidemiology 2017;28: 288–299
An excess risk of lung cancer and its
subtypes at relatively low levels of
cumulative exposure (>0.5 ff/ml-
years), which persisted at least up to
40 years after last exposure.

36. Do we need asbestosis to develop
lung cancer?

37. Lung cancer and asbestos exposure:
asbestosis is not required
Risk
ratio
Non-
smoker
controls
Smoker
controls
Non-smoker insulator
workers
Asbestos
exposure Asbestosis
Smoker insulator
workers
Asbestos
exposure Asbestosis
1.0 10.3 3.6 7.4 14.4 36.8
Both asbestos exposure and asbestosis have higher risks of lung
cancer Markowitz et al.Am J Respir Crit Care Med 2013;188(1):90–96

38. Boutin et al. Am. J. Respir. Crit. Care Med. 1996; 153:444–449.

39. Non-occupational asbestos exposure
1. Para-occupational exposure or take-home exposures
2. Environmental exposure from industrial operations
3. Exposure to commercial asbestos-containing products
4. Naturally occurring asbestos
Noonan CW. Ann Transl Med 2017;5(11):234

40. Para-occupational exposure
The term para-occupational exposure refers to an asbestos-
exposed worker serving as a vector for the transport of fibers to
the household setting. Other terms used include household
contact, take-home exposure or domestic exposure.
The most common activity attributed to para-occupational
exposure is laundering of the contaminated clothes from
workers.
Noonan CW. Ann Transl Med 2017;5(11):234

41. Para-occupational exposure occurs when asbestos-exposed workers
function as vectors for transporting fibers.
Household contacts can be exposed in worker vehicles (A1)
Contact with worker clothes or other dust deposits in the home (A2).

42. Summary OR (and 95% CI) of 5.0 (2.5–10) for para-occupational exposure and
mesothelioma. Summary risk estimates were similar when stratifying by study type
(i.e., case-control or cohort).
Goswami et al. Int. J. Environ. Res. Public Health 2013, 10, 5629-5670

43. Ngai et al. Archives of Biochemistry and Biophysics 2010;502:1–7
1. Oxidative stress theory: free
radical generation
2. Chromosome tangling theory:
3. Adsorption theory: Fibers cause
activation and delivery of
chemical carcinogens
benzo-ɑ-pyrene of cigarette
smoke
4. Chronic inflammation theory:
persistent macrophage
activation

44. Ault et al. Cancer Res. 1995 Feb 15;55(4):792-8.

45. Mechanism for asbestos-induced oncogenesis
Carbone et al.Semin. Oncol. 2002;29:2–17.
Asbestos fibers is very cytotoxic to human
mesothelial cells

46. Yang H et al.Proceedings of the National Academy of
Sciences USA, 2006;103(27):10397–10402

47. Thank you