Defending the Rest Basics on Lung Cancer, Other Cancers and Asbestosis: Review of the B-Read and Pulmonary Function Testing

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1 Defending the Rest Basics on Lung Cancer, Other Cancers and Asbestosis: Review of the B-Read and Pulmonary Function Testing OTHER CANCERS November 2013 Bruce T. Bishop Nancy E. Leary Willcox & Savage 440 Monticello Avenue, Suite 2200 Norfolk, VA

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4 OTHER CANCERS Remember 2 critical medical issues: General Causation Asbestos generally Fiber type/chrysotile Specific Causation 4

5 OTHER CANCERS Remember 2 critical medical issues: General Causation Asbestos generally Fiber type/chrysotile Specific Causation 5

6 ASBESTOS-SELECTED CANCERS National Academy of Sciences Institute of Medicine Committee on Asbestos (National Academy Press 2006) 4-Level classification of the strength of evidence for causal inference Sufficient Suggestive to infer causation Inadequate OR Suggestion of no causal association 6

7 ASBESTOS-SELECTED CANCERS National Academy of Sciences Institute of Medicine Committee on Asbestos (National Academy Press 2006) For the purpose of its charge, designating an association of asbestos with cancers of the designated sites as causal, the committee required the evidence to reach level of sufficient. pg. 3 7

8 ASBESTOS-SELECTED CANCERS National Academy of Sciences Institute of Medicine Committee on Asbestos (National Academy Press 2006) Causal Association Between Specified Cancer & Asbestos CANCER Laryngeal Pharyngeal Stomach Colorectal Esophageal EVIDENCE FOR PRESENCE OR ABSENCE OF CAUSAL RELATIONSHIP TO ASBESTOS Sufficient Suggestive But Not Sufficient Suggestive But Not Sufficient Suggestive But Not Sufficient Inadequate 8

9 IARC MONOGRAPH 2012 A cancer 'hazard' is an agent that is capable of causing cancer under some circumstances, while a cancer 'risk' is an estimate of the carcinogenic effects expected from exposure to a cancer hazard. p. 12 Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

10 IARC MONOGRAPH 2012 The Monographs are an exercise in evaluating cancer hazards, despite the historical presence of the word 'risks' in the title. p. 12 Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

11 IARC MONOGRAPH 2012 The distinction between hazard and risk is important, and the Monographs identify cancer hazards even when risks are very low at current exposure levels, because new uses or unforeseen exposures could engender risks that are significantly higher. p. 12 Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

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13 IARC MONOGRAPH 2012 LARYNX AND OVARY: Causal association clearly established Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

14 Reid 2011 Conclusion: Taken without further analysis, women thought to have ovarian cancer had an increased rate in the metaanalysis if reporting having been exposed to asbestos, compared with reference populations. This result may have occurred because of disease misclassification. pg Reid, A, et al., Does Exposure to Asbestos Cause Ovarian Cancer? A Systemic Literature Review and Meta-analysis, Cancer Epidemiol Biomarkers Prev, 20(7): , 2011.

15 Reid 2011 No study showed a statistically significant trend of ovarian cancer with degree of asbestos exposure. In addition, there was no evidence of a significant trend across studies as grouped exposure increased. pg Reid, A, et al., Does Exposure to Asbestos Cause Ovarian Cancer? A Systemic Literature Review and Meta-analysis, Cancer Epidemiol Biomarkers Prev, 20(7): , 2011.

16 Reid 2011 Meta-analysis techniques cannot account or adjust for the quality of the data contained in the original studies that are used in the meta-analysis. If the original data contain errors of classification, then errors are built into the metaanalysis. pg Reid, A, et al., Does Exposure to Asbestos Cause Ovarian Cancer? A Systemic Literature Review and Meta-analysis, Cancer Epidemiol Biomarkers Prev, 20(7): , 2011.

17 Ahmad 2009 Otolaryngologists should recognize that patients who have been exposed to asbestos (or who have asbestosis) may develop laryngeal carcinoma; but in the absence of evidence, we cannot conclude that their asbestos exposure caused their cancers. As always, we must remain vigilant in distinguishing between the coexistence of two events and a causal link between them. The evidence must be studied carefully whenever a causal link is suggested. pg Ahmad, SM and RT Sataloff, Editorial, Asbestos exposure and laryngeal cancer: Is there an association?, ENT-Ear, Nose & Throat Journal, , 2009.

18 IARC MONOGRAPH 2012 PHARYNX, STOMACH & COLORECTAL: Working group noted a positive association between these cancers and asbestos exposure Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

19 Gamble 2008 None of the various methods to estimate asbestos exposure yielded consistent E-R trends and the strength of the associations were consistently weak or nonexistent for the four types of GI cancers, colon, and rectal cancer. pg. S124 Gamble, J., "Risk of Gastrointestinal Cancers From Inhalation and Ingestion of Asbestos," Regulatory Toxicology and Pharmacology, 52: S124-S153, 2008.

20 IARC MONOGRAPH 2012 Positive association observed in several of the cohort studies with the highest exposures Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

21 Hein 2007 CANCER SITE SMR (98% CI) Female genital organs 1.02 ( ) Intestine (except rectum) 0.57 ( ) Rectum 1.26 ( ) Larynx 1.68 ( Stomach 0.97 ( ) Hein, MJ, et al., Follow-up study of chrysotile textile workers: cohort mortality and exposureresponse, Occup Environ Med, 64: , 2007.

22 IARC MONOGRAPH 2012 DID NOT EVALUATE KIDNEY CANCERS Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

23 Lipworth 2009 For occupational factors, the weight of the evidence does not provide consistent support for the hypothesis that renal cell cancer may be caused by asbestos, gasoline or trichloroethylene exposure. p. 33 Lipworth, L, et al., Epidemiologic characteristics and risk factors for renal cell cancer, Clinical Epidemiology, 1: 33-43,

24 Lipworth 2009 The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. p. 33 Lipworth, L, et al., Epidemiologic characteristics and risk factors for renal cell cancer, Clinical Epidemiology, 1: 33-43,

25 IARC MONOGRAPH 2012 Clinical and epidemiological studies suggest that asbestos may be associated with: 1. Cancer of the larynx (Clearly established-insufficient information on fiber types) 2. Cancer of the ovary (Clearly established) 3. Cancer of the pharynx (Positive association-insufficient information on fiber types) 4. Cancer of the stomach (Positive association-insufficient information on fiber types) 5. Cancer of the colorectum (Positive association-insufficient information on fiber types) 6. Cancer of the oesophagus 25

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28 OTHER CANCERS Remember 2 critical medical issues: General Causation Asbestos generally Fiber type/chrysotile Specific Causation 28

29 ASBESTOS-SELECTED CANCERS National Academy of Sciences Institute of Medicine Committee on Asbestos (National Academy Press 2006) The committee did not consider the issue of fiber type, which was no included in its charge. pg. 3 29

30 OTHER CANCERS Remember 2 critical medical issues: General Causation Asbestos generally Fiber type/chrysotile Specific Causation 30

31 COLORECTAL CANCER Risk factors: The risk of colorectal cancer increases with age; 90% of cases are diagnosed in individuals 50 years of age and older. Modifiable factors associated with increased risk include obesity, physical inactivity, a diet high in red or processed meat, alcohol consumption, long-term smoking, and possibly very low intake of fruits and vegetables. p

32 ORAL CAVITY AND PHARYNX CANCER HPV infection is associated with cancers of the tonsil, base of tongue, and some other sites within the oropharynx and is believed to be transmitted through sexual conduct. p

33 2004 Surgeon General s Report Conclusions 1. The evidence is sufficient to infer a causal relationship between smoking and cancer of the larynx. The Health Consequences of Smoking 2. Together, smoking and alcohol cause most cases of laryngeal cancer in the United States. p. 62

34 IARC MONOGRAPH 2012 While tobacco smoking and alcohol consumption are clearly dominant risk factors for cancer of the pharynx in industrialized countries, these associations between cancer of the pharynx and asbestos remained evidenct in several studies when tobacco and alcohol exposures were considered. p. 257 Source: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Volume 100, A Review of Human Carcinogens, Part C: Arsenic, Metals, Fibres, and Dusts,

35 2004 Surgeon General s Report Conclusions Esophageal Cancer 10.The evidence is sufficient to infer a causal relationship between smoking and cancers of the esophagus. Bladder and Kidney Cancers The Health Consequences of Smoking 13. The evidence is sufficient to infer a causal relationship between smoking and renal cell, renal pelvis, and bladder cancers. p. 324

36 ORAL CAVITY AND PHARYNX CANCER Risk factors: Known risk factors include all forms of smoked and smokeless tobacco products and excessive consumption of alcohol. Many studies have reported a synergism between smoking and alcohol use, resulting in more than 30-fold increased risk for individuals who both smoke and drink heavily. p

37 COLORECTAL CANCER Heredity and medical factors that increase risk include a personal or family history of colorectal cancer and/or polyps, a personal history of chronic inflammatory bowel disease, and certain inherited genetic conditions (e.g., Lynch syndrome, also known as hereditary non-polyposis [FAP]. Studies have also found that individuals with type 2 diabetes are at higher risk of colorectal cancer. p