Genetics and Workplace Issues

1
Genetics and Workplace Issues

• P.A. Schulte, Ph.D.

2
Disclaimer

• The findings and conclusions in this report are
  those of the author and do not necessarily
  represent the views of the National Institute for
  Occupational Safety and Health.

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Research Practice
Regulation/Litigation
Uses
Types

• Inherited genetic factors
• Acquired genetic effects

E
E
4
Application

• Clinical diagnosis
• Worker monitoring screening
• Risk assessment
• Regulation Litigation
• Risk communication
• Risk management

Validation
Discovery
Research
Optimization Transitional Studies Specimen
Banking Database Development Bioinformatics
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Uses
Research Practice
Regulation/Litigation
Types

• Gene-environment interaction
• Mechanistic insight
• Population characterization
• Predictive value

• Inherited genetic factors
• Acquired genetic effects

E
E
6
Sensitive genotype
High risk
D
G
D
E
Resistant genotype
Low risk
D
G
D
Sensitive genotype
Low risk
D
G
D
E
Resistant genotype
Background risk
D
G
D

• EEnvironment GGenetic DDisease

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Research

• Informed consent
• Omissions and deficiencies
• Interpretation/communication
• Simplicity vs. complexity

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Two Categories of Genes Ethical Issues
High Penetrance- High Risk
Low Penetrance- Low Risk

• Privacy concerns
• Stigmatization
• Possibilities for discrimination
• Impact on families
• Psychological distress
• Impact on groups

High High High High Med-High Med-High
Low Low Low Low No-Med Low-Med
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What to tell participants

• Group risk to individual risk assessment
• Variables R2
• GSTT1 4
• Smoking 28
• Ethylene oxide 30
• Small, transitional study
• . . . risk uncertain

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Uses
Research Practice
Regulation/Litigation
Types

• Diagnosis
• Preventive services
• Genetic screening
• Risk management

• Inherited genetic factors
• Acquired genetic effects

E
E
11

• Line between screening, diagnosis, and therapy is
  blurred
• DNA diagnostics
• Pharmacogenetics

12
Golub et al. 1999)
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Genetic Screening
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Rationale for Screening

• Cannot protect hypersusceptibles
• Small number most costly
• Easy to do

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Issues in Screening

• Tests are not validated or ready
• Departs from meritocratic view
• Leads to discrimination/stigmatization
• Violates privacy
• Disproportionately burdens groups
• Violates spirit and intent of OSH laws

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Beryllium and HLA DPB1E69

• Risk of CBD with Glu 69 variant OR 85
  (11-3578) (Richeldi et al, 1993)
• Should prospective employees be screened prior to
  employment?

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Beryllium and HLA DPB1E69

• Predictive Value 7-9
• Other Suspected Variants on Ch6
• No curative treatment for CBD
• CBD occurred in relatively well-controlled areas

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Employer Provided

• Anonymous, voluntary third-party testing
• Employee received individual results
• Employer received group results

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• Exclusion of workers as a result of genetic
  testing runs contrary to the spirit intent of
  the OSH Act of 1970. It wrongly puts the burden
  of controlling toxic substances on the worker who
  is denied employment because of a supposed
  sensitivity.
• Employers should make the workplace safe for all
  workers, rather than deprive some workers of
  their livelihood in the name of safety.
  (Bingham, 1980)

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ACOEM Position Statement (1994)Genetic Screening
in the Workplace

• Conclusions
• Guiding ethical principles voluntary, informed
  consent, confidentiality, due respect for
  autonomy, equity, and privacy
• Until extensively validated, tests should be
  considered as a form of human investigation

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Uses
Research Practice
Regulation/Litigation
Types

• Risk assessment
• Workers compensation
• Tort litigation
• Standard setting

• Inherited genetic factors
• Acquired genetic effects

E
E
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Regulation/Litigation

• Workers compensation or tort liability first
  uses
• Prohibitions against use in hiring
• Executive Order
• Various states
• ADA EEOC interpretation
• Possible use in standard setting
• Use in risk assessment

23
GSTTI Risk Estimates of Methylene Chloride

• Monte-Carlo simulation PBPK models
• Median estimate 30 higher when GSTTI
  polymorphism not included
• 
  (El-Masri et al., 1999)

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Characteristics of the Genetic Tests

• Test for
• Disease
• Purpose of Test
• Analytic validity
• Clinical validity
• Clinical utility
• Ethical, legal, social, safeguards

PMP 22 Carpal Tunnel Syndrome Assess work
relatedness of a workers compensation claim No
published information found No published
information found Not applicable No informed
consent
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Uses
Research Practice
Regulation/Litigation
Types

• Inherited genetic factors
• Acquired genetic effects

E

• Effects of exposure
• Linkage to disease
• Mechanistic insight
• Early warning

E
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Acquired Effects Research

• Large body of cytogenetic research
• Health effects and exposure
• Group risks
• Gene-expression technologies
• Toxicogenomics
• Transcriptomics
• Proteomics
• Metabolomics

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Wang et al. 2005
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Uses
Research Practice
Regulation/Litigation
Types

• Inherited genetic factors
• Acquired genetic effects

E

• Genetic monitoring
• Intervention evaluation
• Risk profiling

E
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Acquired Effects Practice

• Genetic monitoring
• Similar to biological monitoring
• Problem no individual interpretation
• Widely practiced for radiation exposures
• Useful to evaluate interventions
• Risk profiling

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Uses
Research Practice
Regulation/Litigation
Types

• Inherited genetic factors
• Acquired genetic effects

E

• Risk assessment
• Pre-market testing
• Workers compensation
• Tort litigation
• Standard setting

E
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Regulation/Litigation

• Cytogenetic model
• If a pattern can be evaluated as a biomarker of
  effect
• variable in research
• endpoint in intervention studies
• target in standards
• evidence of harm
• How regulatory bodies will accept, evaluate, use,
  interpret array data

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Regulation/Litigation

• Enables pre-market testing
• Could be used as evidence in workers
  compensation/litigation
• Standard setting
• Risk assessment

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the road to acceptance?

• How does a regulator deal with risk assessment
  data that scientists are often unable to
  interpret data that some companies are anxious
  to submit and others to withhold?
• How does this same regulator evaluate information
  that is produced without a universally
  recognized standard for laboratory protocols or
  data formats?
• Should companies submit all data voluntarily
  without knowing whether regulators will be able
  to understand it, and if and exactly how they
  will use it?

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the road to acceptance?

• What if data that cannot be interpreted now are
  later shown to indicate toxicity perhaps at a low
  level that could not be detected in animal
  testing (Freeman, 2004)?
• The critical issue in using genomics data is that
  if and when it is interpretable in terms of
  population risks what will be the regulatory
  focuses if sensitive subgroups are identified?
• Will controls be required to protect these groups
  or will risk management strategies, such as
  communications, be applied?

Freeman K, Toxicogenomics data the road to
acceptance. Environ Health Perspect 2004
A678-A685.