What are the implications of LIFEPATH evidence for future … · 2019. 4. 1. · SES. BMI, obesity...
Transcript of What are the implications of LIFEPATH evidence for future … · 2019. 4. 1. · SES. BMI, obesity...
What are the implications of LIFEPATH evidence for future research on lifestyle and environment related diseases ?
Béatrice Fervers
Scientific Advisory Board
27/03/2019
Lifepath evidence suggests the need to think differently about social factors in future research on
lifestyle and environment related diseases
• Effect modification by social factors
• Early life is the game changer: Left truncation of SES data
• Impact of Lifepath evidence on intervention studies on life style factors
• Biological embodiment of social inequalities
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Socioeconomic disadvantage associated with poor health outcomes later in live, partlymediated by behavioural factors (McCrory et al, Stringhini et al)
SES BMI, obesityAging
Poor health outcomeslater in life
Physical activity
Tobacco, Alcohol
Socioeconomic position is an independent risk factor, like smoking or hypertension Stringhini et al, 2017 and 2018
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Individual level SES
Area level SES
Socioeconomic disadvantage associated with poor health outcomes later in live, partlymediated by behavioural factors (McCrory et al, Stringhini et al)
SES BMI, obesityAging
Poor health outcomeslater in life
Physical activity
Tobacco, Alcohol
Socioeconomic position is an independent risk factor, like smoking or hypertension Stringhini et al, 2017 and 2018
NCDsCancer
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Individual level SES
Area level SES
Epidemiologic evidence for effect modificationby socioeconomic position (SEP)
Excess risk of mortality associated with a 10-μg/m3 short-term NO2
increase, stratified by SES and long-term NO2 concentrations- Paris, France, 2004–2009 Deguen et al. Plos One 2016
SES Pollutant exposure
Poor health in later life NCDs, Cancer, Child
respiratory diseases, birthweight
Deguen et al 2016; Cloughery et al 2014; Chiu 2013; Shandardkass 2009; Islam 2011
Low SES associated with increased pollutant vulnerability
Low SES more exposed to air pollution
SES independant risk factor
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Effect Modification by Socioeconomic Position (SEP)
• Activation of similar pathways• Synergistic effects• Social factors may act as
inflammation-inducing trigger • Increased inflammatory
responsivity to environmentalfactors
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Early life is the game changer McCrory et al, 2017; Layte et al, 2017; Kivimaki et al, 2018
• Advanced mean age at study entry of many current cohorts– Examples
• E3N-EPIC cohort France: 52.8 years
• Constance cohort: 35 to 50 years
• Left truncation of lifecourse data– Loss of accuracy and misclassification
– Depending on the exposure effect model, overestimation or underestimation of the association with disease risk • Hazelbag 2015, Leu 2007, Zhai et al. in preparation
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• Critical period model– Exposure during a specific (sensitive) period has lasting or lifelong effect on the
structure or physical functioning of organs– “biological programming” or “latency model”
• Critical period model with later effect modifiers– Later life factors may modify the effect of an exposure during a critical period of
development on later disease risk : synergism or antagonism.
• Cumulative model – Multiple effects accumulate over the life course. – Cumulative damage to biological systems– During developmental periods susceptibility may be greater– Sequence or trajectory of accumulation may be important
• Chain of risk model/Trigger model– Sequence of linked exposures where one leads on to the next. – Various intermediate factors between early life and adult health – such as lifestyle,
educational attainment, social class and health behaviours– Timing of exposures may affect disease risk
Effect models over the life course
Jacob et al. , WHO 2017Lifepath final meeting 27/03/2019 - SAB - Béatrice Fervers 8
• Critical period model– Exposure during a specific (sensitive) period has lasting or lifelong effect on the
structure or physical functioning of organs– “biological programming” or “latency model”
• Critical period model with later effect modifiers– Later life factors may modify the effect of an exposure during a critical period of
development on later disease risk : synergism or antagonism.
• Cumulative model – Multiple effects accumulate over the life course. – Cumulative damage to biological systems– During developmental periods susceptibility may be greater– Sequence or trajectory of accumulation may be important
• Chain of risk model/Trigger model– Sequence of linked exposures where one leads on to the next. – Various intermediate factors between early life and adult health – such as lifestyle,
educational attainment, social class and health behaviours– Timing of exposures may affect disease risk
Effect models over the life course:Left truncation of exposure data
Jacob et al. , WHO 2017Lifepath final meeting 27/03/2019 - SAB - Béatrice Fervers 9
Early life is the game changer McCrory et al, 2017; Layte et al, 2017; Kivimaki et al, 2018
• Include detailed data on social factor variables, including parental information, childhood SES, lifecourse changes, psychosocial stress, etc
• Include spatial variables, ie. neighborhood SES
• Retrospective collection of early life data
• Transgenerational cohorts (E4N)
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Impact of Lifepath evidence on intervention studieson life style factors : adopting an enlarged vision
• Target of intervention– Complementarity of
intervention on intermediate risk behaviours and on the social deprivation itself
• Timing– Adolescents and young
adults: pivoltal life stage for intervention research
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Impact of Lifepath evidence on intervention studieson life style factors : adopting an enlarged vision
• Target of intervention– Complementarity of
intervention on intermediate risk behaviours and on the social deprivation itself
• Timing– Adolescents and young
adults: pivoltal life stage for intervention research
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• Low grade inflammation, DNA methylation– Key caracteristics of carcinogens
• Chronic inflammation increases cancer risk– Contributes to multiple hallmarks of cancer – Involved in tumor initiation and promotion
• Pro inflammatory environment– Nutrition and obesity induced inflammation– Infection?– Stress and psychological pathways
• Conflicting evidence regarding cancer risk for individuals exposed to stressful life events• Mechanisms involved are not well established (inflammation, catecholaminergic system) • Stressful life events vs low SES associated stress• Future research to disentangle the pathways : omics approaches, internal exposome
Figure 6 Biological embodiment of social inequalities Castagné et al 2016, Barboza Solis et al, 2016; Fiorito et al, 2017 and 2019; McCrory et al, 2019; Berger et al, 2019
10 key characteristics of carcinogens
Grivennikov 2010, Cell
Smith EHP 2015
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Independant risk factorBiologicl embodiment
Upstream causal factorEffect modifyer
Impact ofLifepath evidence on the understanding of the exposome : lifecourse exposures
metabolism, endogenous
hormones, body
morphology, physical
activity, gut micro flora,
inflammation, aging etc.
Internalradiation, infectious
agents, chemical
contaminants and
pollutants, diet, lifestyle
factors (e.g. tobacco,
alcohol), occupation,
medical interventions,
etc.
Specific external
social capital, education,
financial status,
psychological stress, urban-
rural environment, climate,
etc
General external
Wild CP (2012) Int. J. Epidemiol, 41: 24-32Lifepath final meeting 27/03/2019 - SAB - Béatrice Fervers 14
Conclusions
• Lifepath evidence has important implications on design for future studies– Need to think differently about collection and analyses of social factors in future
epidemiology studies
• Lifepath consortium to provide recommendations for researchers• Detailed data on lifecourse social factors
– Individual and spatial data– Repeated measurements to allow trajectory analyses– Include data on protective factors/positive adaptations, including internal assets and
external resources (relisience)
• Investigate effect modification and synergistic effects• Recommendations for lifestyle intervention studies to focus on the intervention
and the social factors• Disentangle the pathways
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