Seoul National University College of Medicine, Korea

Daehee Kang, MD, PhD

dhkang@snu.ac.kr

Personalized Preventive Carefor Cancer

Bukchon Hanok Village

SeoulNationalUniversityCollegeofMedicineAlumniAssociationofNorthAmerica,Inc.

Contents∗ Increased importance of personalized preventive care∗ Aging and health∗ Paradigm shift in medicine∗ Precision medicine

∗ Evidence of personalized preventive research on cancer∗ Past efforts∗ Current interests on cancer

∗ Preparation for future needs∗ Collaboration is key∗ The next cohort for cancer in epidemiology

Increasedimportanceofpersonalizedpreventivecare

PartI.

3

WeliveLONGER!

Data from United Nations, World Population Prospects, the 2015 Revision

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

80.00

90.0019

50 -1

955

1955

-19

6019

60 -1

965

1965

-197

019

70 -1

975

1975

-198

019

80 -1

985

1985

-199

019

90 -1

995

1995

-200

020

00 -2

005

2005

-201

020

10 -2

015

2015

-202

020

20 -2

025

2025

-203

020

30 -2

035

2035

-204

020

40 -2

045

2045

-20

5020

50 -2

055

2055

-206

020

60 -2

065

2065

-207

020

70 -2

075

2075

-208

020

80 -2

085

2085

-209

020

90 -2

095

2095

-210

0

Life

Exp

ecta

ncy

at B

irth

(yea

rs)

Years

Female Male

Female:72.74Male:68.29

∗ Extendedlifeexpectancy∗ Averageincreaseof20yearsduringthepastfewdecades(world)

∗ Percentageofolderpopulationgrowing

AgingPopulation

Source: Petsko, Genome Biology, 2008

6

Theviciouscyclewillcontinue,Increasingproportionofelderlypopulation(65+):1950-2050

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050

World OECD EU27 USA Korea Japan

Source: OECD.Stat

KoreaJapan

PopulationPyramid:Korea2010-2060

Population Pyramid, from KOSIS.kr/statPpulation/main.jsp#

male female

13% of population age>65 in yr 201540% of population age>65 by yr 2060

BUT…doweliveHEALTHIERLife?

∗ Healthylifeexpectancy(HALE)∗ Averagenumberofyearsthataperson

canexpecttolivein“full”health

Salomon et al. Lancet. 2012

Men

Women

Korea

Korea

Sex YearLife

Expectancy(LE)

Healthy Life Expectancy

(HALE)

Increase in LE

Increase in HALE

Men1990 68.1 60.6

8.4 7.32010 76.5 67.9

Women1990 76.2 67.1

6.5 5.52010 82.7 72.6

Wesufferfromchronicdiseases!

Data from GBD 2013 @ http://viz.healthmetricsandevaluation.org/gbd-compare/

GlobalBurdenofDiseases(GBD)In1990

GlobalBurdenofDiseases(GBD)In2013

Source: OECD Health Data

Korea

Japan

10

Andthatcomeswithit…- Increasedhealthcarespending -

The Global Economic Cost of Cancer. American Cancer Society. 2011

• Impactofprematuredeathanddisabilityfromcancerworldwidewas$895billionin2008

• Represents1.5%oftheworld’sgrossdomesticproduct(GDP)

• Theeconomictollfromcancerisnearly19%higherthanheartdisease

• Theanalysisdidnotincludedirectmedicalcosts

Better,moreexpensiveDiagnostictoolsTreatmentmodalities

Unraveltheproblem- Atitscausalorigin-

Dans et al. Lancet. 2011

∗ Importanceofpreventivecare∗ “Anounceofpreventionisworthapoundofcure”

- BenjaminFranklin

Leftshiftofnaturalcourseofdisease

ExposurePathologicChanges Symptoms

Diagnosis

StageofClinicalDisease

StageofSubclinicalDisease

StageofSusceptibility

StageofRecovery,DisabilityorDeath

Therapy

Newparadigm:Leftshiftofdiseaseprogressiontoimprovedhealth

Naturalhistoryofdiseaseprogression

Pathtofuturemedicine

Ordinary medicinePersonalized medicine and prevention

via precision and prediction

GovernmentsinAction!- UnitedStates-

http://news.yahoo.com/obama-calls-major-personalized-medicine-initiative-030325518.htmlhttp://news.yahoo.com/nih-taking-first-steps-huge-precision-medicine-project-111203692--politics.html

15

the right treatment at the right time

- Launchofanewprecisionmedicineinitiative,a$215millionprojecttocollectdataongenomes

January,2015

Dr.FrancisCollins,NIHDirector:

“…empoweranyperson,anywhereintheU.S.”inwhat’scalledthePMICohortProgram

“NIHwillprovide fundingtoVanderbiltU.[foracollaborativepilotproject]withVerily(formerGoogleLifeSciences)”

- ObamatoaskCongress for$309million[in2017fortheinitiativescaleup]- Amassivedatabasewilltrackat least1millionvolunteersby2019

February,2016

Dr.FrancisCollinsatSNUH

PrecisionmedicineinKorea- MinistryofHealthandWelfare-

Source: Korea Health Industry Development Institute

Core area Project Department

Infrastructure establishment for precision medicine cohort

New precision medicine cohortCohort

Enhance existing cohort and biobanks

Prepare systemic coordination for precision medicine-based big data

Standardization and linkage of genomic-medical data

Medical record and public health based big data

Establishment of open data hub Information security and standardization

Develop precision medicine based health services

Development of precision medicine based artificial intelligence Public health big data

Precision medicine based clinical experiment system Omics

Development of precision medicine based healthcare service model Mobile health care

Improve policies and laws related to precision medicine and developmanpower

Improvement of laws, policies, and regulations Law/Policy

Train professionals in the field of precision medicine -

Theuseof“KoreanChip”will helprealizeprecisionmedicineinKorea:∗ Genomicinformationon100,000Koreans∗ Linkagewithcoreinfrastructuresuchascohort,healthcareindustry, electronichealthrecords,andbigdata

∗ NationalCancerCenter(NCC): Large-scalecancerprecisionmedicinecohort∗ Geneticdataof1million cancerpatients∗ Providebasis fordevelopment of

chemotherapeuticagents∗ Bigdatadrivenpreventionofcancer

recurrence

PrecisionmedicineinAcademia- SeoulNationalUniversityBundang Hospital-

Healthcare Innovation Park (HIP) & Seoul National University Bundang Hospital (SNUBH)

- SeoulNationalUniversityBundang Hospital (SNUBH)toleadBigData-basedprecisionmedicineinKorea,anewleapsinceitsembarkasthenation’sfirstfullydigitalized,paperlesshospital

- Establishedtaskforceforcollaborative researchonprecisionmedicine

18

Chul-Hee Lee,SNUBHPresident&CEO:

“Therealizationofprecisionmedicineforeachandeverypatientmaybeadvancedthrough theintegrateduseofhospitaldatabasesystemandgenomic information.”

October,2015

Evidenceofpersonalizedpreventiveresearchoncancer

PartII.

19

Today,it’sallaboutprediction

Newparadigmshift:AJCC’sprognostic,statisticallybasedriskcalculatorsin2016

• Cancerstobeevaluated:• breast,colon,prostate,lung,melanoma,head

&neck• Foreachcancertype,riskmodelsmust:

• Predictoverallsurvival ordeath• Passall16criteria(13inclusion +3exclusion)

Riskpredictionusingbiomarkers

Song, Lee and Kang , JJCO, 2014

SeoulBreastCancerStudy(SeBCS)

Discriminativevaluesofbreastcancerriskmodelsusinggeneticandnon-geneticfactorsfromSeoulBreastCancerStudy(SeBCS)

SNUH AMC Borame hospital EUMC Community-based

• NumberofSubjects(2001-2007)• Cases:4040• Controls:3946

• Originalpapers(2003~2012)• SeBCS:51papers• Collaboration:24papers

Anexampleofbreastcancersurvivalprediction

Song, Kang et al., PLoS One, 2015.

A.Tumorsubtype: rs166870 B.Tumorsubtype:rs10825036

Comparisonofthepredictivepowersofdisease-freesurvival(DFS)forbreastcancer:§ Modelwithcombinedclinical(age,TNMstage,tumorsubtype)andgeneticvariables tendedto

havebetterpredictivepowersoverall§ Geneticfactorsplayedroleindistinguishing highandlowriskgroupswhenusingcombined

prognosticmarkers

• Overall:• Harrell’sCclinical model =70.92%• Harrell’sCcombined model =71.37%• p =0.03

• HR+HER2-:• Harrell’sCclinical model =65.08%• Harrell’s Ccombined model =66.69%• p<0.01

• HR- HER2-:• Harrell’sCclinical model =63.26%• Harrell’sCcombined model =65.88%• p<0.01

PreparationforfutureneedsPartIII.

24

Thespeedofknowledgeaccumulation

Smallerworld,biggerdata

Source: IBM 2013 @ https://www-304.ibm.com/connections/blogs/ibmx86/entry/biginsights_for_big_data?lang=ko

Wiredworld(theInternet)

Globaltransportationnetwork

Infiniteaccumulationofdatawithdatabasetechnology

Moreknowledgeandinsight

Collaborativeworkisimportantinthefuture

∗ Theartofcommunicationandteamwork∗ Withprofessionalsfromvarioussectors∗ Withinaglobalsetting

IdentificationCard

NextGenerationCohort• Needmorepower• Outcomeheterogeneity• Gene-environmentinteraction• Widerdistributionofexposurevariables

AnextgenerationlargegenomiccohortinKorea

InNeedofaNextGenerationCohort

TakingAdvantageofKorea’sUniqueEnvironment

• Biennial HealthExaminationbyLaw(NationalHealthInsuranceCorporation)• NationalPersonalIdentification System(13-digitresidence registrationnumber)

Birthday(6)YYMMDD

Registration(7)Sex-Birthplace-Order-Hidden

Driver’slicense Passport

ExamplesofPreviousCohorts

è AutomaticRepeatedFollow-up&PossibleIntegrationtoSecondaryData

HEXA(HealthExamineesStudy)since2004CentralizedDatabaseStorage

&Biobanking

• Men:Women=2:1

• Meanageatrecruitment (years)§ Men:women=53.7(±8.2):52.6(±7.6)

DiseaseGroup 2018 2023

All-sitecancer 11,749 17,800

Ischemicheartdisease 2,663 4,034

CVA 6,308 9,556

• Totalnumberofquestionnaires n=1,303§ SES,Pastmedicalhistory,lifestylehabits,socio-

psychologicalfactors,reproductivefactors,dietaryhabits(including106SQ-FFQ)

§ Clinical&physicalexamination

HEXAsubjects recruit2004-2012(n=162,142)

EstimatedNumberofIncidentCasesofSelectedDiseasesComposition ofHEXAQuestionnaire &Labdata

HEXAresearchactivities

WhyAsia?

∗ 2/3ofworld’spopulation∗ 4/5ofnewcanceroccurrenceby2020

∗ Widerdistributionofexposurevariablesinrelativelyhomogenousethnicbackgrounds∗ smoking,diet,environment

∗ Rapidchangesincertainpersonalhabits∗ reproductivefactors,urbanization,

etc.

AsiaCohortConsortium(ACC)

Asia CohortConsortium

China

Malaysia

Japan

Singapore

Korea

NCI Cohort ConsortiumBPC3

EPICUK Biobank

8~10 countries, over 1,000,000 participants

IndiaBangladesh

AsiaCohortConsortium- Challengesforcollaborativeresearch-

Song, Kang et al, J Epidemiol 2012

Challenges:

• dataharmonization• resolutionofethicalandlegalissues• establishmentofprotocolsforbiologic

samplesandtransferagreements• fundingprocurement• preciseexposureassessment

MGEL(Molecular&GenomicEpidemiologyLaboratory)

Personalized

Predictive Preventive

Participatory

Prospective Precise

“P4 medicine will transform the healthcare industry”- Hood Leroy

Building Evidence through “6 P” Research!

THANKYOU!dhkang@snu.ac.kr