Exposoom: waarom, wat, hoe?

Tim Nawrot; email: tim.nawrot@uhasselt.be

Antwerpen, 21 mei ‘19

Genetic factors are not major cause of chronic disease

Rappaport et al. Plos One 2016

GWAS vs EWAS

Niet-differentiële misclassificatie

300 250

100 150

case control

exposed

unexposed

Cases Controls

Exposed 300-30+10 = 280 250-25+15 = 240

Unexposed 100-10+30 = 120 150-15+25 = 160

OR= 300 x 150

100 x 250= 1.80

OR= 280 x 160

120 x 240= 1.56

10% of all people are exposed are misclassified as unexposed and 10% of all unexposed are misclassified as exposed.

Effects all groups

Differential misclassification

300 250

100 150

case control

exposed

unexposed

Cases Controls

Exposed 300+20 = 320 250

Unexposed 100-20 = 80 150

OR= 300 x 150

100 x 250= 1.80

OR= 320 x 150

80 x 250= 2.40

20% of unexposed cases, but not controls are misclassified as exposed.

Different extent in cases and controls

Over the life-time

Major cancer risk factors

Risk Factor Comments

Tobacco Implement WHO FCTC; taxation; bans on advertising; regulations on smoking in public places; counter the introduction into low and middle‐income countries (LMIC)

Alcohol Avoid harmful use; increase awareness; taxation and regulation

Physical inactivity,overweight and obesity

Increase physical activity and improve weight control; major area where research is needed

Unhealthy diet Relatively limited understanding on how specific nutrients or dietary patterns affect cancer risk

Infections HBV, HPV, H. pylori, HCV; vaccination; avoid contaminated injections

Radiation UV light; ionising radiation; medical diagnostic, indoor radon

Environmental carcinogens Naturally occurring (arsenic, aflatoxins); Industrial (air pollution, asbestos)

Occupation Regulatory measures; avoid “exporting” at‐risk exposures to LMIC

Reproductive factors and hormones 

Allied to earlier age at menarche, later age at first live birth; fewer children; shorter duration of breast feeding

Adapted from Franceschi and Wild, Molec. Oncol., 7: 1-13, 2013See also IARC Monographs Volume 100

Hart- en vaatziekten een geintegreerde benadering

Cell Volume 157, Issue 1, 27 March 2014, Pages 241–253

Exposome: how

Biosensors (1)

Nature 2011

Caratine Tartrate

Biosensors (2)

Nature 2011

Fetal exposure to black carbon

Bove et al. Nature Communications (in press)

Telomere biology over the life span

Martens et al. JAMA Pediatrics 2017

Telomere length an exposome marker

Determinants of telomere length in early life

Socioeconomic class

Low EducationModerate Education

Low Occupational Status

Moderate Occupational Status

-10

-5

0

5Cord Blood

n=1405

% d

iffer

ence

in T

L

Martens et al. Int J Epidemiol (in press)

Martens D et al. JAMA Pediat 2017

Prenatal air pollution exposure and telomere length at birth

PM

PMPM

5 µg/m3 prenatal PM2.5

Placenta: 7.7% shorter

Cord blood: 6.6% shorter

Conclusies

Meeste aandoeningen multifactorieel Exposoom als antwoord op genoom Ruis op omgevingsdata geeft onderschatting van

werkelijke risico. De haalbaarheid van exposoom is gedeeltelijk

aangetoond Levensloop benadering