Exposoom: waarom, wat, hoe? · Exposoom als antwoord op genoom Ruis op omgevingsdata geeft...
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Transcript of Exposoom: waarom, wat, hoe? · Exposoom als antwoord op genoom Ruis op omgevingsdata geeft...
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
