OCCUPATIONAL LUNG CANCER

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OCCUPATIONAL LUNG CANCER

Anwar Jusuf, Agus Dwi Susanto

Department of Pulmonology & Respiratory Medicine, Faculty of Medicine Department of Pulmonology & Respiratory Medicine, Faculty of Medicine University Of Indonesia - Persahabatan Hospital-Jakarta

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INTRODUCTION

“ Occupational cancer is a workplace dangerous problems “

Source :

International Metal Workers

Federation 2007

(3)

“

Occupational cancer is

the forgotten epidemic “

ILO

“ It estimates occupational cancers make up almost

one-third of all work-related deaths “

Source : Source : International Metal Workers International Metal Workers Federation 2007

(4)

How about occupational lung cancer ?

Occupational lung cancer

“

one of a big problem in occupational cancer “

“

“Inhalation is a most causes“Inhalation is a most causes“

(5)

Etiology of Lung Cancer

٨٧% ١٣%

Smoking Other factors

Occupational lung cancer

Environment & Environment & occupational occupational exposure exposure Smoking is Smoking is the most the most environmental environmental cause in cause in communities communities

(6)

EPIDEMIOLOGY



_{USA data}

1. Aproximately 6-10% cancers were attributable to

occupational exposure occupational exposure  5% is a lung cancer 5% is a lung cancer

2. Estimated 9000-10.000 men and 900-1900 women

develop lung cancer annually as a result of occupational develop lung cancer annually as a result of occupational

exposureexposure

3. Estimated 3-17% of male lung cancer were attributable to

(7)

Increased risk of lung cancer induced by

occupational exposure :



_{Sweden (proportion 9,5%)}



_Germany

(8)

The Global disease burden from occupational carcinogens

(9)

 _{Travis et al}_{Travis et al}

Reported analyses of Surveillance,Epidemiology, and End

Results (SEER)

Results (SEER)  period 1973-1987. period 1973-1987.

•

• The percentage of lung cancers that were adenocarcinoma The percentage of lung cancers that were adenocarcinoma

in all race-sex groups combined increased to 32 percent, in all race-sex groups combined increased to 32 percent,

surpassing squamous cell carcinoma as the most surpassing squamous cell carcinoma as the most

frequentlyoccurring histologic type. frequentlyoccurring histologic type.

•

• Squamous cell carcinoma, however,continues to constitute Squamous cell carcinoma, however,continues to constitute

a large proportion (29 percent) of lung tumors.a large proportion (29 percent) of lung tumors.

Epidemiology of histological types occupational Epidemiology of histological types occupational lung cancer

(10)

CARCINOGENS IN WORK PLACE

(11)

 _{Almost 150 carcinogen or probable carcinogen in}_{Almost 150 carcinogen or probable carcinogen in}

workplace ( IARC)

Until now

Until now there is :there is :

- 21 agents to be carcinogenic for the human lung

- 5 agents as probable human lung carcinogen

- 4 agents to be possible human lung carcinogen

 _{The single most important occupational "chemical"}_{The single most important occupational "chemical"}

cause is asbestos



(12)

Agents/processes to be carcinogen for the human Agents/processes to be carcinogen for the human

lung (IARC) lung (IARC)

 _{Arsenic/arsenic compounds}_{Arsenic/arsenic compounds}  _Asbestos_Asbestos

 _{Chromium/chromium compounds}_{Chromium/chromium compounds}  _{Mustard gas}_{Mustard gas}

 _{Undergound hematite mining}_{Undergound hematite mining}  _{Coal gasification}_{Coal gasification}

 _{Coke production}_{Coke production}

 _{Iron and steel founding}_{Iron and steel founding}

 _{Talc containing asbestiform fibers}_{Talc containing asbestiform fibers}

 _{Alumunium production}_{Alumunium production}

 _Soot_Soot

 _Radon_Radon

 _{Sulfuric acid mist}_{Sulfuric acid mist}

 _{Bis (chloromethyl) ether and}_{Bis (chloromethyl) ether and}

chloromethyl methyl ether chloromethyl methyl ether

 _{Cadmium/cadmium compounds}_{Cadmium/cadmium compounds}  _Nickel_Nickel

 _{Spray painting}_{Spray painting}

 _{2,3,7,8-tetrachlorodibenzo-para-}

2,3,7,8-tetrachlorodibenzo-para-dioxin dioxin

 _{Berrylium/berrylium compounds}_{Berrylium/berrylium compounds}  _{Paint manufacturing/painting}_{Paint manufacturing/painting}  _{Chrystalline silica}_{Chrystalline silica}

International Agency for Research on Cancer (IARC)

(13)

Agents/processes to be probable human lung Agents/processes to be probable human lung

carcinogens (IARC) carcinogens (IARC)

(14)

Agents/processes to be possible human lung Agents/processes to be possible human lung

carcinogens (IARC) carcinogens (IARC)

(15)

Strength of evidence

Site

Site High-risk substance or circumtanceHigh-risk substance or circumtance

Table. Occupational lung carcinogen (IARC)

Health prespect 2004; 112: 1447-59.

(16)

Relative risk



_{Relative risk for lung cancer caused by}

occupational carcinogen exposure (exclude radon)

aproximately 1,6

WHO report 2002WHO report 2002



_{Tobacco and many workplace carcinogens}



 “ Multiplicative risk”“ Multiplicative risk”



(17)

Table. Estimated relative risks for lung carcinogens

WHO report 2002

(18)

Relative risk of

lung cancer due

(19)

Is histological types of lung cancer

associated with spesific agent ?



_{No study has unequivocally demonstrated any one}

lung cancer cell type to be uniquely associated

with a spesific agent



_{Many studies have attempted to identify}

differences in distribution of histologic types :

-

Arsenic exposure



adenocarcinomas

-

(bis)

chloromethyl ether

or to

uranium /radon

(20)

- Nickel

- Nickel  small cell carcinomas and epidermoid small cell carcinomas and epidermoid

- Vinyl chloride

- Vinyl chloride  large cell cancers large cell cancers - Mustard gas

- Mustard gas  Squamous cells carcinoma or Squamous cells carcinoma or

undifferentiated lung carcinoma undifferentiated lung carcinoma -

- Silica Silica  bronchogenic carcinoma or bronchogenic carcinoma or

undifferentiated lung carcinomaundifferentiated lung carcinoma

 _Asbestos_Asbestos

- All histologic type of lung cancer maybe seen

- Some studies have shown a preponderance of

(21)

Pathogenesis

 _{Mechanism occupational agent induced lung cancer, almost}_{Mechanism occupational agent induced lung cancer, almost}

still unclear

still unclear  _Arsenic_Arsenic



 “ “ Induced chromosom malformation in mamalian Induced chromosom malformation in mamalian

cells also in perifer lymphocyte worker who cells also in perifer lymphocyte worker who

exposed arsenic “exposed arsenic “

 _Radon_Radon



 “ “ Induced epitelial break and genetic mutation epitelial Induced epitelial break and genetic mutation epitelial

(22)

Asbestos induced lung cancer

 _{Mechanism are not well understood}_{Mechanism are not well understood}  _{Some possible mechanism :}_{Some possible mechanism :}

1. DNA damaged by reactive oxygen species induced by fiber

2. Direct DNA damaged by physical interactions between

fibres and target cellsfibres and target cells

3. Enhacement of cells proliferation by fiber

4. Fibre-provocated chronic inflammatory cytokines and

growth factorsgrowth factors

5. Actions by fibre as co-carcinogens or carrier of chemical

(23)

Pathogenesis smoking induced lung cancer and interaction with

occupational lung carcinogen

(24)



_{Asbestos is the most occupational agent}

induced lung cancer with relative risk 2,0

WHO report 2002WHO report 2002



_{Aproximately 6% lung cancer cases in men and}

1% in women caused by asbestos exposure



_{Asbestos caused lung cancer independent or}

synergistically with cigarretes smoking

ASBESTOS AND LUNG CANCER

(25)

Epidemiology asbestos induced lung cancer

 _USA_USA

In 1990

In 1990  aproximately 1200 cases lung cancer /years aproximately 1200 cases lung cancer /years

 _{Europe :}_{Europe :}



 11,6% lung cancer cases in Nederland 11,6% lung cancer cases in Nederland 

 18,3% cases in Italy 18,3% cases in Italy

 _Asia_Asia

China

China  in 1993 there was 67 cases lung cancer caused by in 1993 there was 67 cases lung cancer caused by asbestos exposure

(26)

Chest 2003; 123:21-49

(27)

Tobacco - Asbestos

(28)

(29)

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AMPHIBOLE



_{High carcinogenicity}



High carcinogenicity

_{High carcinogenicity}

amphibole

_amphibole

maybe

_maybe

caused by several factors :



long biopersistence

_{long biopersistence}



Fe

+ +

in fibers could catalisis product

_{in fibers could catalisis product}

reactive oxigen radicals

(31)

(32)

(33)

CHRYSOTILE



_{Carcinogenicity still debate & controversy}

Some study :



_Chrysotile

_{still carcinogen , but less compare}

amphibole.



_{One of reason,}

_t

_{here is no asbestos that 100%}

chrysotile

(34)

Other study :



_{New study showed}

_chrysotile

_{there is no carcinogen}

effect or low carcinogenicity



_{Hodgson et al.}



chrysotile

exposure low risk caused cancer

(35)

Bernstein et al



_{Study in rat showed that biopersistence and}

clearance

chrysotile

_chrysotile

better than

_{better than}

amphibole

_amphibole

.

_.



_Chrysotile

_{fibers had}

_clearance

_{fast in lung}

(short retension in lung).

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DIAGNOSIS & MANAGEMENT

 _{Diagnosis and management occupationally induced lung}_{Diagnosis and management occupationally induced lung}

cancer is not any differently from lung cancer generally

Anamnesis :

 _{Full occupational and enviromental histories should be}_{Full occupational and enviromental histories should be}

considered

 _{Hostory of smoking}_{Hostory of smoking}___{a significant cause}_{a significant cause}  _{A latency periode}_{A latency periode}___{12 – 40 years}_{12 – 40 years}

(38)

Investigation

 _{Imaging ( Thorax X-ray dan CT)}_{Imaging ( Thorax X-ray dan CT)}  _{Sputum cytology}_{Sputum cytology}

 _Biopsy_Biopsy

 _Bronchoscopy_Bronchoscopy

 _{Mineralogic analysis}_{Mineralogic analysis}

To evaluate relevance of occupational exposures to the

development of lung cancer

- Bronchoalveolar fluid

- Bronchoalveolar fluid  BAL BAL

- Peripheral blood lymphocyte transformation response to

berryilumberryilum

- The are no another reliable cellular and serologic test

(39)

PREVENTION

Worker selection Exposure control

Smoking cessation policy National regulatory

“

“ Primary prevention is important to Primary prevention is important to prevent occupational lung cancer”

(40)

Worker selection Worker selection Exposure control Exposure control Smoking cessation Smoking cessation policy policy National regulatory National regulatory

•• Preemployement recruitment Preemployement recruitment  low risk low risk

•• There are no guideline for worker There are no guideline for worker

selection regarding lung cancer selection regarding lung cancer

except identifying smokers except identifying smokers

 Nonsmokers, if exposed asbestos Nonsmokers, if exposed asbestos

•• Limiting occupational exposure Limiting occupational exposure

•• Not fully protect, maybe minimalized Not fully protect, maybe minimalized

risk for lung cancerrisk for lung cancer

•• Most of the agents synergisticMost of the agents synergistic

relationship with tobacco exposurerelationship with tobacco exposure

•• Smoking cessation in and out work place Smoking cessation in and out work place

 lower overall risk of lung cancerlower overall risk of lung cancer

••Focus on eliminiation (or minimization) Focus on eliminiation (or minimization)

••Substitute with a less haxardous materialsSubstitute with a less haxardous materials

••Minimize exposure through enginering Minimize exposure through enginering

modificationmodification

••Personal protectivePersonal protective

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CONCLUSION

 _{The was estimated increased risk of lung cancer induced}_{The was estimated increased risk of lung cancer induced}

by occupational exposure

 _{Exposure occupational agent and cigarettes smoking had}_{Exposure occupational agent and cigarettes smoking had}

m

multiplicative risk for lung cancerultiplicative risk for lung cancer

 _{A s}_{A s}_{ingle most important occupational "chemical"}_{ingle most important occupational "chemical"}

cause of lung cancer is blue asbestos or amphibole

 _{Diagnosis and management occupationally induced lung}_{Diagnosis and management occupationally induced lung}

cancer is not any differently from lung cancer generally

cancer is not any differently from lung cancer generally  _{Primary prevention is most important act to prevent}_{Primary prevention is most important act to prevent}

occupational lung cancer

(43)