Recent Advances in Occupational and Environmental Health Research

Howard Hu MD MPH ScD

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

• Our heritage• http://www.youtube.com/watch?v=AdC0efvJXRQ

The Dalla Lana School of Public Health

• 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 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?

25 years of research on a global pollutant: lead

• Paint, pipes, leaded-gasoline, 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.*

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

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

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

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

78

80

82

84

86

88

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

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 ???

• 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

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

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, 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

Map of Ultrafine Particles in Toronto

Evans lab: Sabaliauskas et al. Atm Env 201524

• 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 dean.dlsph@utoronto.ca )