recent advances in occupational and environmental health research howard hu md mph scd
TRANSCRIPT
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Recent Advances in Occupational and Environmental Health Research
Howard Hu MD MPH ScD
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Career on a slide…
Boston City Hospital: Internal Medicine, 1982-1985
1985-2005: Full Professor with Tenure
Parents immigrate from Shanghai & Beijing 1946
Born in New York City
Brown University
Albert Einstein Medical School
Shipyards & Public Health
Summers of ’73,’74: shipyards
2006-2012 Department Chair, U Michigan…
Dean
July 2012
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• Our heritage• http://www.youtube.com/watch?v=AdC0efvJXRQ
The Dalla Lana School of Public Health
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• 2008: Recreated • 2013: Became Full Faculty• 2014: Merged with Institute
for Health Policy, Management & Evaluation
• 2014: Created Waakabinesse-Bryce Institute for Health with $10M Dan Family gift
• 2015: Merging with Joint Centre for Bioethics
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Outline
• The micro: understanding the “true” footprint of occupational & environmental risk factors on health Advances in molecular epidemiology, exposure
science, “big data”
• The macro: Built environment, mega-cities, big data Climate change, planetary health
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Genes v. Environment?Studies of twins
• Concordance of disease occurrence in monozygotic (MZ) v dizygotic (DZ) twins high in MZ/ low in DZ
• high heritability (genes!)
medium in MZ/ medium in DZ• low heritability; high influence by environmental factors
shared by twins
low in MZ/ low in DZ• low heritability; high influence by environmental factors
specific to each twin
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The unexpectedly large influence of et al., (NEJM, 2000) environment on cancers: the Scandinavian Twin Study
• Genetics only explains 27% of breast cancer• “Shared” environment only 6%• Individual environment explains 67%
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Similarly, we can examine concordance in other CDs
• Parkinson’s: ~20-30%• Alzheimer’s (Late onset, >65 yo): ~40%• Essential Hypertension: <40%• Osteoporosis: <40%• Schizophrenia: <40%• Gene-environment interactions ??
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The 3 most difficult challenges to environmental epi research
• Exposure• Exposure• Exposure
i.e., measuring, estimating, modeling exposures to chemical toxicants, the relevant timing, and the dose-response relationship
What metric of exposure is biologically most important?• Current? Cumulative? Peak? At some specific lifestage?
(Timing)
What is the dose-response?• Monotonic linear? Threshold? U-shaped?
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25 years of research on a global pollutant: lead
• Paint, pipes, leaded-gasoline, food cans, many other products…
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The hidden problem: The impact of cumulative lead exposure (bone lead levels) Hu et al, 1996
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BONE LEAD AND HYPERTENSION In community-exposed men.*
Lowest quartile Highest quartile0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
Odds of developing hypertension
*Adjusted for age, body mass index, family history of hypertension, smoking, alcohol ingestion, dietary calcium, dietary sodium
Hu et al, 1996
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BONE LEAD AND MORTALITYIn community-exposed men*
Weisskopf et al, 2009
Cancer All Cause Cardio-vasc
Ischemic HD
0123456789
Hazard ratio hi v. low bone lead
*Adjusted for age, body mass index, smoking, race
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Low bone lead High bone lead0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
Rate ratio of cataracts
*Adjusting for age, smoking
BONE LEAD AND CATARACTSIn community-exposed men*
Schaumberg et al, 2004
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Lead, the Hemochromatosis genes C282Y/H63D, and Cognition
• More intracellular iron and lead Synergistic promotion of
oxidation
• HFE carrier adults had worse cognition given same lead burden
Wildtype
HFE carriers
Wang et al, 2006
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78
80
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84
86
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90
92
1stquartile
2ndquartile
3rdquartile
4thquartile
Mental developmentindex score
Fetal exposure to mom’s mobilized bone lead stores independently predict poorer offspring IQ at age 2 years
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Knowledge Translation
• New recommendations for adults explosed to lead
• New recommendations for lead and pregnancy
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New Direction: Is early life lead exposure a risk factor for Alzheimer’s ???
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• Post-mortem brains Alzheimer’s v Control
• Epigenome discovery• Transmembrane
Protein 59 identified responsible for post-
translational glycosylation of APP
leads to retention of APP in the Golgi apparatus
• Studies on lead exposure in progress
Bakulski et al, in press
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EXPOSOMICS- Proposes to use
available measures of external human exposures
- …combined with advanced, high through-put methods
- …to develop a comprehensive profile of human exposures over the life course.
Wild C, 2012
Example
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Near term strategy: chop up the lifecourse into discrete, simultaneously observed segments
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The macro
• Built environment, mega-cities, big data • Climate change, planetary health
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- Population-based cohort study of >230,000 Ontarians aged 18+ years
- Questionnaires, BiospecimensPhysical measurements, Clinical data
- Data linkage to administrative health data (from universal health coverage system x 20+ years)
-The Institute for Clinical Evaluative Sciences
www.OntarioHealthStudy.ca
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Map of Ultrafine Particles in Toronto
Evans lab: Sabaliauskas et al. Atm Env 201524
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• Merging of health, environment, social data
• Policy-relevant research using “Big Data” resources
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Climate change: Spectacular inequities
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The ultimate experiment…