Occupational Cancers and its prevention in an Industrial setting

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1. OCCUPATIONAL CANCERS Moderator: Dr. Yogesh Kumar Presenter : Dr. S. Hemavathe KAHER J.N. MEDICAL COLLEGE, BELAGAVI DEPARTMENT OF COMMUNITY MEDICINE

2. Content Introduction Disease Burden Agents classified by the IARC Occupational Cancers Lung Cancer Bladder Cancer Mesothelioma Leukaemia Skin cancer Rare Cancers Prevention 22-07-2022 Dept of Community Medicine 2

3. Introduction Occupational cancers are caused by exposure of carcinogens at workplace. Carcinogen is a substance or agent which is responsible for the development of the cancer or increases the risk of developing cancer. Most common - lung cancer, bladder cancer, and mesothelioma . 22-07-2022 Dept of Community Medicine 3

4. Characteristics of Occupational cancer Appear after prolonged exposure Latent period -10-25 years Disease may develop even after the cessation of exposure Average age incidence is earlier than cancer Localization of tumours is remarkably constant in any one occupation 22-07-2022 Dept of Community Medicine 4

5. Disease Burden Currently cancer deaths -occupational exposures - 4-20% for developed countries . 6,66,000 fatal work-related cancers occur every year IARC(WHO) globally 14 million new cancer every year , 8.2 million people die due to cancers. Incidence increase by 70% and mortality 78% by the year 2035 Doll and Peto - 4% of all cancer deaths , 12.5% of lung cancer deaths 22-07-2022 Dept of Community Medicine 5 Hunter’s Diseases of Occupations, 10 th Edition

6. 22-07-2022 Dept of Community Medicine 6 Group 1 Carcinogenic to humans Sufficient evidence of carcinogenicity in humans and in experimental animals 120 agents Group 2A Probably carcinogenic to humans Limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals 82 Group 2B Possibly carcinogenic to humans Limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals 302 Group 3 Not classifiable as to its carcinogenicity to humans Inadequate evidence of carcinogenicity in humans and in experimental animals 501 Group 4 Probably not carcinogenic to humans Evidence suggesting lack of carcinogenicity in humans and in experimental animals 1 Agents classified by the IARC Hunter’s Diseases of Occupations, 10 th Edition

7. LUNG CANCER 54-75% of all occupational cancers. 17-29% of all lung cancers among men. Difficult to investigate the role of a potential carcinogenic agent on lung cancer due to the presence of various confounders E.g. cigarette smoking, socioeconomic status, air pollution, diet, etc. 22-07-2022 Dept of Community Medicine 7

8. Cont., Carcinogenic agents - a dose-response relationship between cumulative exposure and the risk for lung cancer has been estimated. Lag period of 10-30 years from initial exposure to the time point when relative risk increases to significance level. 22-07-2022 Dept of Community Medicine 8

9. 22-07-2022 Dept of Community Medicine 9 Sl No Agent category Agents 1 Ionizing radiation-all types - 2 Chemicals and mixtures Ether, coal-tar pitch, soot, sulfur mustard, diesel exhausts 3 Occupations Aluminium production, coal gasification, coke production , hematite mining (underground), iron and steel founding, painting, rubber production industry 4 Metals Arsenic, beryllium, cadmium, chromium, and nickel 5 Dust and fibers Asbestos and silica dust 6 Personal habits Indoor emissions from household combustion Tobacco smoke 7 Other exposures MOPP (vincristine-prednisone-nitrogen mustard- procarbazine mixture) Group 1 carcinogens(IARC) with sufficient evidence of causing lung cancer in humans Hunter’s Diseases of Occupations, 10 th Edition

10. Trend Analysis of Occupational Lung Cancer from Coke Oven Emission Exposure - China, 2008-2019 C oke oven emissions-induced lung cancer - found in the coke manufacturing industries. W orkers exposed to higher levels of polycyclic aromatic hydrocarbons in different workplaces had a high risk of occupational lung cancer 22-07-2022 Dept of Community Medicine 10 Abulikemu A, Wang D, Hu W, Shen M, Sun X, Duan H. Trend Analysis of Occupational Lung Cancer from Coke Oven Emission Exposure - China, 2008-2019. China CDC Wkly. 2022 Apr 29;4(17):353-357. doi : 10.46234/ccdcw2022.034. PMID: 35547635; PMCID: PMC9081898.

11. BLADDER CANCER 10 th most common cancer globally Important risk factor for the development of bladder cancer second to smoking. 20% of all bladder cancers in industrialized countries. Unusual incidences of bladder cancer in industry were reported by doctors in late 19th century . 22-07-2022 Dept of Community Medicine 11

12. Cont., Case and Hosker , retrospective cohort study  exceptionally high incidence of bladder carcinoma in workers of British rubber industry . 22-07-2022 Dept of Community Medicine 12

13. Cont., Later on, several other occupational carcinogens have been found associated with increased risk of bladder carcinoma like PAHS in the aluminum and coal tar industries. High incidence of bladder cancer among painters with a relative risk between 1.2 and 1.5. Higher incidence of bladder cancer among drivers with relative risk between 1.3 to 2.2 22-07-2022 Dept of Community Medicine 13

14. Group 1 carcinogens (IARC) with sufficient evidence of causing bladder cancer in humans Aluminium, arsenic, auramine, magenta 4- aminobiphenyl, benzidine, chlornaphazine, cyclophosphamide, 2- naphthylamine, ortho-toluidine Painting, rubber production industry Tobacco smoking, X-radiation, gamma-radiation. 22-07-2022 Dept of Community Medicine 14

15. Mesothelioma Very aggressive kind of malignancy- pleura, peritoneum, pericardium. 1950 it was found to be linked with occupational exposure of asbestos and classified as occupational disease . Long latency period (up to 40 years) with very poor prognosis, as most patients die within 1 year of diagnosis. 22-07-2022 Dept of Community Medicine 15

16. Cont., Studies have shown that in UK and Finland 97% and 90% of mesothelioma cases, respectively, are related to occupational exposure of asbestos. 22-07-2022 Dept of Community Medicine 16

17. Leukaemia Malignant transformation of hematopoietic cells, which produce abnormal leukemic cells  suppresses the production of normal blood cells. It has varied clinical presentations, prognosis, and response to treatment. Number of potential risk - but till date exposure to ionizing radiation, benzene(plastics, rubbers, drugs, dyes), and alkylating agents have been substantiated as the only hazards for leukemia. 22-07-2022 Dept of Community Medicine 17

18. 20 th century association between ionizing radiation and leukemia - due to uncontrolled exposure of medical personnel and patients to the radiations, used for diagnostic and therapeutic purposes. Next to Radiation exposure, benzene is considered as the second best-documented risk factor for leukemia Chemical properties have led to its widespread use -in production of chemicals, plastics, pharmaceuticals, paints, synthetic rubbers, oil processing, etc. 22-07-2022 Dept of Community Medicine 18

19. Cont., Cytostatic drugs , especially chemotherapeutic regimens which contain alkylating agents like busulfan, cyclophosphamide, chlorambucil, etc. -risk factor –leukemia(AML) Workers exposed - cytostatic drugs at any level starting from production, transportation, distribution, and preparation to administration to patients. 22-07-2022 Dept of Community Medicine 19

20. Group 1 carcinogens (IARC) with sufficient evidence of leukaemia in humans Azathioprine, benzene, busulfan Cyclophosphamide, cyclosporine Epstein-Barr virus, Helicobacter pylori, hepatitis C virus, HIV, Kaposi sarcoma herpes virus Tobacco smoking X-radiation, gamma-radiation 22-07-2022 Dept of Community Medicine 20

21. Skin Cancer London surgeon Sir Percival Pott. 1775 -squamous cell carcinoma of the scrotum among chimney sweepers , 1 st highlighted the link Exposure to distilling tar and pitch- increased with time due to industrial revolution . Early 20th century -association between -ionizing radiation - hands of doctors and technicians -exposed to X-rays 22-07-2022 Dept of Community Medicine 21

22. Group 1 carcinogens (IARC) with sufficient evidence of Skin Cancer in humans Skin (Melanoma) Solar radiation Ultraviolet-emitting tanning devices Polychlorinated biphenyls(transformers, capacitors) Skin (other malignant neoplasms) Arsenic and inorganic arsenic compounds ,Azathioprine, cyclosporine Coal-tar distillation, coal-tar pitch Mineral oils, shale oils (LPG) Solar radiation, X-radiation, gamma radiation Soot(incomplete burning of organic matter) 22-07-2022 Dept of Community Medicine 22

23. Rare Cancers Cancers of Sinuses and Nasal Cavity Nasopharyngeal cancer Laryngeal cancer Stomach cancer Hepatocellular carcinoma Angiosarcoma of the liver Cancer of the pancreas Colorectal cancers Brain tumours Breast cancer 22-07-2022 Dept of Community Medicine 23

24. Cancers of the Sinuses and Nasal cavity 1950s- higher risk among nickel (batteries) refiners , Clydach plant in South Wales. High risk of ethmoid sinus cancer in furniture makers in Buckinghamshire. Cluster of mixed cell type, mixed-site sinus cancers emerged in the Northampton area due to leather goods manufacture - in particular, boots and shoes 22-07-2022 Dept of Community Medicine 24

25. Cont., 1960s, a large excess risk for Sino nasal cancer(adenocarcinomas), has been repeatedly documented among workers in wood-related occupations. Leather industry, formaldehyde(preservative), nickel(batteries, coins), hexavalent chromium compounds(welding), textile industry. 22-07-2022 Dept of Community Medicine 25

26. Cont., Case control studies, the higher risk for wood workers was specifically associated with sinonasal adenocarcinoma . Risk for smoking  squamous cell carcinomas also undifferentiated carcinomas. Major risk SNC - tobacco smoking 20 % and occupation 30 % 22-07-2022 Dept of Community Medicine 26

27. NASOPHARYNGEAL CANCER Common in -geographical regions and ethnic groups in Southeast Asia. Large study- United States -25619 workers (865 708 person-years) employed in 10 US formaldehyde ( germicide, disinfectant , preservative) -producing or using facilities among workers - extensive quantitative exposure assessment -increased risk. 22-07-2022 Dept of Community Medicine 27

28. LARYNGEAL CANCER Several occupations- truck drivers, leather workers, metal workers etc., Among carcinogens identified by IARC, only exposure to strong inorganic mists, including sulphuric acid, is accepted as a group I carcinogen Industries with exposure to these acids include manufacture of isopropanol (isopropyl alcohol), synthetic ethanol (ethyl alcohol), sulphuric acid, nitric acid, phosphate fertilizer, soap, detergent, lead batteries, copper smelting, pickling and other acid treatment of metals. 22-07-2022 Dept of Community Medicine 28

29. Cont., 2009, IARC classified as sufficient the evidence on asbestos and laryngeal cancer. No evidence of a dose-response effect. 22-07-2022 Dept of Community Medicine 29

30. STOMACH CANCER Helicobacter pylori infection - main risks for gastric cancer. Nitrosamines- proven and potent animal carcinogens -linked to human exposure in that the secondary amines in fish , preserved meat, vegetables could be converted to nitrosamines by gastric hydrochloric acid. Quarrymen and stone cutters, coal and metal miners, rubber workers, construction workers, chemical and petrochemical workers, workers exposed to dioxins and farmers. Specific exposures - asbestos, coal dust, nitrogen oxides, mineral, metal dusts, wood dusts, nitrosamines and others. 22-07-2022 Dept of Community Medicine 30

31. HEPATOCELLULAR CARCINOMA Hepatitis B and C viruses (Health care professionals), exposure to aflatoxins( farmers ) -risk factors for hepatocellular carcinoma. Exposure to vinyl chloride(pipes, wire, cable) -hepatocellular carcinoma. 22-07-2022 Dept of Community Medicine 31

32. ANGIOSARCOMA OF THE LIVER Tumour that is extremely rare in the general population- been unequivocally associated with exposure to vinyl chloride monomer. Men employed in the manufacture of PVC resins - 1 st evidence. 22-07-2022 Dept of Community Medicine 32

33. CANCER OF THE PANCREAS Chemists, radiologists. Among the chemical agents suspected -some chlorinated organic solvents and chlorinated pesticides, including DDT (dichlorodiphenyltrichloroethane). 22-07-2022 Dept of Community Medicine 33

34. COLORECTAL CANCERS Tentative association between colorectal cancer and the manufacture of the anti-knock agent, tetraethyl lead(Jet fuel). Lack of physical activity due to sedentary occupation -main determinants - it can be indirectly implicated 22-07-2022 Dept of Community Medicine 34

35. BRAIN TUMOURS Mortality rates are rising in industrialized countries Increased risk laboratory workers, petrochemical plant workers and embalmers. Potential chemical exposures - organic solvents, as well as ionizing radiation. Recently lead, electric fields or magnetic fields from residential or occupational exposure-associated with increased risk 22-07-2022 Dept of Community Medicine 35

36. BREAST CANCER Women employed in jobs that entail exposure to organic solvents . Dry cleaners, hairdressers, aircraft maintenance, textiles, electronics manufacturing and others. Studies -women engaged in shift work may have an increased risk of breast cancer. 15-20% of the working population in Europe and the United States is engaged in shift work that involves night work. More prevalent -healthcare, industrial manufacturing, mining, transport, communication, leisure and hospitality sectors. 22-07-2022 Dept of Community Medicine 36

37. Cont., Night work is disruptive for the circadian clock. Rodent models - association of tumour development with a disruption of the circadian system with reduced nocturnal melatonin concentrations Epidemiological studies on nurses engaged in shift work at night and of female flight attendants have shown a modest increased risk But have potential uncontrolled confounding by reproductive factors and cosmic radiation. If these risks are proven, night shift -most important occupation-related risk factors for cancer. 22-07-2022 Dept of Community Medicine 37

38. Prevention of occupational cancer Necessary to know of the existence of proven aetiological agents and then to know that separation of humans from exposure to the agent is feasible. Primary prevention  implementation of general measures for control of exposures Such measures not focusing on one agent, but through improvements in work practices and changes in industrial processes  result in control of a wide range of occupational exposures. 22-07-2022 Dept of Community Medicine 38

39. Cont., In industrialized countries  improvements in prevention and control of exposure to occupational carcinogens. Improvement of work conditions and control of occupational carcinogens in newly industrialized countries or in developing countries is a major challenge . 22-07-2022 Dept of Community Medicine 39

40. Hierarchy of preventive measures Implementation step Suggested interventions Step 1 Core Develop regulatory and enforcement control of carcinogens Avoid introducing known carcinogens to the work places Step 2 Expanded Monitor and reduce occupational exposure to carcinogens Organize health surveillance of exposed workers Step 3 Desired Develop comprehensive worker's health programs based on primary prevention to improve working and living conditions Substitute carcinogens with less dangerous substances 22-07-2022 Dept of Community Medicine 40

41. PRIMARY PREVENTION All occupational cancers are preventable if carcinogens have been successfully identified. Elimination or drastic reduction at the level of exposure. In practice it is difficult for a number of reasons: a) Exposure defined -complex mixture example painters- apart from general hygiene measurements 22-07-2022 Dept of Community Medicine 41

42. Cont., b)Substance/process with societal importance like Benzene -basic building block aromatic industry - 'exclusion' is difficult to conceive, also natural ingredient of fossil fuels c) Crucial to reduce the level of exposure to very low levels that are unlikely to cause disease. d) Substitute , Asbestos - hazardous (amphibole)  longer period to exclude chrysotile asbestos from use. e) Economic importance-Radon exposure - extremely difficult, yet the need to mine for metals in these environments remains. 22-07-2022 Dept of Community Medicine 42

43. Cont., Exposure - reduced level, continues, every effort should be made to shorten the duration of exposure and to reduce exposure to very low levels. Earlier the action, the earlier the effect of reduction of exposure will be recorded. 22-07-2022 Dept of Community Medicine 43

44. SECONDARY PREVENTION Earlier the neoplastic process is detected, the easier it should be to cure the patient. In practice, this is not so clear cut secondary prevention strategies for occupational cancers Whole purpose of detecting cancer is to cure or prevent other cases of cancer. Eliminating a known cause ensures that, at least for the future, the need for treatment is obviated. 22-07-2022 Dept of Community Medicine 44

45. Occupational research institutes Central Institute of Mining and Fuel Research , Dhanbad National Institute of Occupational Health , Ahmedabad National environmental engineering research institute , Nagpur All India Institute of Hygiene and Public Health , West Bengal IIT, Kanpur Council of Scientific & Industrial Research (CSIR),New Delhi 22-07-2022 Dept of Community Medicine 45

46. Reference K. Park, Textbook of Preventive and Social Medicine, 26 th edition IAPSM ,Textbook of Community Medicine, 1 st edition Hunter’s Diseases of Occupations, 10 th Edition Abulikemu A, Wang D, Hu W, Shen M, Sun X, Duan H. Trend Analysis of Occupational Lung Cancer from Coke Oven Emission Exposure - China, 2008-2019. China CDC Wkly. 2022 Apr 29;4(17):353-357. doi : 10.46234/ccdcw2022.034. PMID: 35547635; PMCID: PMC9081898. Saha RK. Occupational Health in India. Annals of Global Health. 2018; 84(3), pp. 330–333. DOI: https://doi.org/10.29024/aogh.2302 22-07-2022 Dept of Community Medicine 46

47. 22-07-2022 Dept of Community Medicine 47 Thank You