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Chinese Benzene Cohort Study. 74,828 exposed and 35,805 unexposed workers Leukemia deaths: RR 2.3, 95% CI 1.1-5.0 Malignant lymphoma deaths: RR 4.5, 95% CI 1.3-28.4 No deaths from multiple myeloma in either population. Wong and Raabe, 2000.

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Chinese Benzene Cohort Study


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chinese benzene cohort study
Chinese Benzene Cohort Study
  • 74,828 exposed and 35,805 unexposed workers
  • Leukemia deaths: RR 2.3, 95% CI 1.1-5.0
  • Malignant lymphoma deaths: RR 4.5, 95% CI 1.3-28.4
  • No deaths from multiple myeloma in either population
meta analysis of risk of multiple myeloma in petroleum workers
Meta-Analysis of Risk of Multiple Myeloma in Petroleum Workers
  • 22 cohort studies of >250,000 workers
  • 220.93 deaths expected; 205 observed
  • SMR 0.93; 95% CI 0.81-1.07

Bergsagel et al; Blood, 1999

nested case control study of multiple myeloma and aml
Nested Case Control Study of Multiple Myeloma and AML
  • >18,000 petroleum distribution workers
  • Up to 5 controls for each of 11 cases with multiple myeloma and 13 with AML
  • Cumulative mean exposure (ppm-yrs THC):
    • MM 672; controls 800
    • AML 773; controls 837
        • Wong, Trent & Harris, 1999
why is it harder to find an elevated smr for mm than for aml in benzene exposed cohorts
Why is it harder to find an elevated SMR for MM than for AML in benzene-exposed cohorts?
  • Benzene does not cause MM
  • Benzene is a relatively less potent myelogen than it is a leukemogen
  • Benzene is as or more potent a myelogen than it is a leukemogen, but the background incidence of MM is less than AML
  • The latency period for MM is longer than for AML
healthy worker effect reasons specific to hematopoietic cancer
Healthy Worker Effect: Reasons Specific to Hematopoietic Cancer
  • Acute Myelogenous Leukemia
    • Down’s syndrome, Fanconi’s anemia, etc
    • Status post cancer chemotherapy
  • Non-Hodgkin’s Lymphoma
    • HIV AIDs
    • Immune suppression diseases or therapies
exposure dose relationships in determining causality

Exposure Dose Relationships in Determining Causality

Is this a useful approach when there are only small numbers and borderline statistical significance?

challenges to epidemiological identification of environmental causes of cancer
Challenges to Epidemiological Identification of Environmental Causes of Cancer
  • Cancer as a final common pathway
  • Unknown susceptibility factors
  • Uncertain exposure levels
  • Powerless negative
  • Cluster fallacy
different levels of certainty required for decisions
Different Levels of Certainty Required for Decisions
  • SCIENTIFIC (p < .05)
  • TORT (p < .50)
  • REGULATORY (p = whatever)
is relative risk greater than two required for proof of causation carruth and goldstein 2001
Is Relative Risk Greater Than Two Required for Proof of Causation?(Carruth and Goldstein, 2001)

Threshold: Required to support inference of causation

12

Threshold: Determinative of ultimate issue

2

Not required for inference of causation

14

Sufficient for inference of causation (not clear if required)

1

Total # of published decisions

29

is relative risk greater than two required for admissibility carruth and goldstein 2001

Required for admissibility

10

Not required for admissibility

11

Total # of published cases

21

Is Relative Risk Greater Than Two Required for Admissibility?(Carruth and Goldstein, 2001)
slide17
Cases Before and After Daubert II Addressing Whether Relative Risk Greater Than Two is Required for Admissibility of Causation Opinion

Before

Daubert II

Daubert II

and After

Required

0

10

Not Required

5

6

Not Considered

9

1

shortcomings of occupational epidemiology for establishing an odds ratio for a specific risk
Shortcomings of Occupational Epidemiology for Establishing an Odds Ratio for a Specific Risk
  • Healthy worker effect
  • Inadequate exposure data
  • Dilution of high risk group
  • Appropriateness of time period