Transcript Name of speaker - McGill University

Recent Advances in Occupational
and Environmental Health Research
Howard Hu MD MPH ScD
Career on a
slide…
Dean
Summers of ’73,’74: shipyards
Parents immigrate from
Shanghai & Beijing 1946
Born in New York City
July 2012
Brown University
Albert Einstein
Medical School
2006-2012 Department Chair, U Michigan…
Shipyards &
Public Health
Boston City Hospital:
Internal Medicine, 1982-1985
19852005:
Full
Professor
with
Tenure
The Dalla Lana
School of Public Health
• Our heritage
• http://www.youtube.com/watch?v=AdC0efvJXRQ
• 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
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
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
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%
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 ??
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 doseresponse 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?
25 years of research on a global pollutant: lead
• Paint, pipes, leadedgasoline, food cans,
many other products…
The hidden problem: The impact of cumulative
lead exposure (bone lead levels) Hu et al, 1996
BONE LEAD AND HYPERTENSION
In community-exposed men.*
2
Hu et al, 1996
1.8
1.6
1.4
1.2
1
Odds of developing hypertension
0.8
0.6
0.4
0.2
0
Lowest
quartile
Highest
quartile
*Adjusted for age, body mass index, family history of hypertension,
smoking, alcohol ingestion, dietary calcium, dietary sodium
BONE LEAD AND MORTALITY
In community-exposed men*
10
Weisskopf et al, 2009
8
6
Hazard ratio hi v. low
bone lead
4
2
0
Cancer
All
Cause
Cardio- Ischemic
vasc
HD
*Adjusted for age, body mass index, smoking, race
BONE LEAD AND CATARACTS
In community-exposed men*
Schaumberg et al, 2004
1.8
1.6
1.4
1.2
1
0.8
Rate ratio of cataracts
0.6
0.4
0.2
0
Low bone
lead
High bone
lead
*Adjusting for age, smoking
Lead, the Hemochromatosis genes
C282Y/H63D, and Cognition
• More intracellular iron
and lead
Wang et al, 2006
Wildtype
 Synergistic promotion of
oxidation
• HFE carrier adults had
worse cognition given
same lead burden
HFE carriers
Fetal exposure to mom’s mobilized bone lead stores
independently predict poorer offspring IQ at age 2 years
92
90
88
86
Mental development
index score
84
82
80
78
1st
2nd
3rd
quartile quartile quartile
4th
quartile
Knowledge Translation
• New recommendations for
adults explosed to lead
• New recommendations for
lead and pregnancy
New Direction: Is early life lead exposure
a risk factor for Alzheimer’s ???
Bakulski et al, in press
• Post-mortem brains
 Alzheimer’s v Control
• Epigenome discovery
• Transmembrane
Protein 59 identified
 responsible for posttranslational
glycosylation of APP
 leads to retention of
APP in the Golgi
apparatus
• Studies on lead
exposure in progress
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.
Example
Wild C, 2012
Near term strategy: chop up the lifecourse into
discrete, simultaneously observed segments
The macro
• Built environment, mega-cities, big data
• Climate change, planetary health
- Population-based cohort study of >230,000
Ontarians aged 18+ years
- Questionnaires, Biospecimens
Physical 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
Map of Ultrafine Particles in Toronto
24Evans lab: Sabaliauskas et al. Atm Env 2015
• Merging of
health,
environment,
social data
• Policy-relevant
research using
“Big Data”
resources
Climate change: Spectacular inequities
The ultimate
experiment…
Thanks!
(This ppt available on request
from [email protected] )