Recent Advances in Occupational and Environmental Health Research

Recent Advances in Occupational and Environmental Health Research Howard Hu MD MPH Sc. D

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 -19852005: Full Professor with Tenure

The Dalla Lana School of Public Health • Our heritage • http: //www. youtube. com/watch? v=Ad. C 0 efv. JXRQ

• 2008: Recreated • 2013: Became Full Faculty • 2014: Merged with Institute for Health Policy, Management & Evaluation • 2014: Created Waakabinesse-Bryce Institute for Health with $10 M 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 § 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* 9 8 7 6 5 4 3 2 1 0 Weisskopf et al, 2009 Hazard ratio hi v. low bone lead Cancer All Cause Cardiovasc Ischemic 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 C 282 Y/H 63 D, 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

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. Ontario. Health. Study. ca

Map of Ultrafine Particles in Toronto 24 Evans 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 dean. dlsph@utoronto. ca )