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

sergio cima

633666

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

Lifepath final meeting 27/03/2019 - SAB - Béatrice Fervers 2

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


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


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


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


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


• 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)


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


• 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


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


what are the implications of lifepath evidence for future … · 2019. 4. 1. · ses. bmi, obesity...

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