IARC Biobank

Maimuna MENDY mendym@iarc.fr

Challenges and Opportunities of the Italian Hub of Population Biobanks (HIBP)

March 9th, 2012 Istituto Superiore di Sanità

Structure of the talk

Introduction

EPIC biobank.

IARC Biobank

Biospecimen science research

Challenges

IARC’s mission is to collaborate with the

international community to conduct research on Cancer.

The Laboratory services & Biobank Group was formed in 2010 (managed in the Office of DIR).

13 Research Groups: epidemilogists and lab based

EPIC sample collection

A population-based

IARC based collections Population-based collections Disease-based collections

diverse biological sample collections Studies conducted world-wide using

different study designs

Introduction

EPIC BIOBANK

Epidemiology study; co-ordinated by

Prof Elio Riboli (IARC, now at Imperial college, London).

Include 22 collaborating centres in the 10 countries

Multifactorial investigation of – Lifestyle – Environmental and Genetic factors

and their interactions

Centralized database kept at IARC; Include clinical data; dietary and non-dietary data

Data flow from cancer registry, clinics, outpatients, GP’s, death registries & screening program.

Collaborating centres and participating states

Participating states Questionnaire Q+Blood

France 74 524 28 053 Italy 47 749 47 725 Spain 41 440 39 579 UK 87 942 43 141

Netherland 40 072 36 318

Greece 28 555 28 483 Germany 53 091 50 678 Sweden 53 826 53 781 Denmark 57 054 56 131 Norway 37 215 31 000

EPIC

End point data imported periodically in the main database.

30 mLs venous blood – 20 mLs citrated plasma

+ 10mLs dry 28 aliquots of 500 ul

– Plasma (red straws) – Serum (yellow straws) – buffy coat (blue straws) – RBC (green straws)

28 aliquots x 300,000 subjects = 8.4 million aliquots stored

Half in each EPIC centre, half at IARC

Plus: 12 X 110,000 = 1.3 million in Sweden and Denmark

Blood collection and storage 1992-1998

EPIC end-point projects

Methodological issues

Dietary patterns

Food preparation

& cancer risk

Cancer sites

EPIC-Elderly

Gen-EPIC

EUR-Gast

EPIC Nutrient Database (ENDB)

Gen-AIR

Obesity, physical activity & other lifestyle factors

Reproductive and hormonal factors

EPIC-Heart INTERACT

Biospecimen usage-EPIC end point

0100002000030000400005000060000700008000090000

*EPIC-heart (2010-2011) Interact (2007-2009)

Retrieval (straws)No. of individualsDNA extractionsshipment packages

*EPIC-heart received new EU FP7 funding to study 15,000 CVD cases (2012-2017)

Biospecimen usage-EPIC end-point

Retrieval DNA extraction

0

500

1000

1500

2000

2500

3000

3500

KidneyLUNGUADTMelanoma

A poly-user biobank

IARC Biobank activities

Sample Management

Biospecimen science research

Pre analytical processing

services

Archiving storage

monitoring

LIMS (SAMI)

Retrieval Aliquoting

DNA Extraction & quantification

International guidelines

& protocols (Evidence-based)

Centralization of IARC’s biological sample collection

• Condcuct inventory of resources • Annotation and validation • Developed in-house LIMS (SAMI) • Importation of various databases

and sample information into the centralized database

• Provide linkage with other databases (epidemiology and clinical)

• Provide linkage between primary and derived samples.

• Data safety and confidentiality – Controlled access – Users have different level of

access.

Sample collections

16%

3%

33%

13%

2%

3%

1%2%

2%

17%

1%

2%

2%

BiopsyBlood spotBone marrowBuffyCoagulated bloodDNAExfoliated cellsHairLeucocytesLymphocytesNailOral cellsParaff in blockParaff in sectionsPlasmaRBCSerumSlide cytologySlide histologyUrineWhole

Plasma

buffy

RBC

Blood spot

Close to 1.5 million samples Started collection in early 1970’s 30+ projects conducted in over 50

countries. Study designs: case series, case

control, prevalence and screening studies.

Diverse sample types; blood, tissues, cells, dried blood spot etc.

0.5%

24.5%

21%

0.1%

4.4%

23.8%

3.6% 0.3%

3%

0.7%

3.6%

3.9%

1%

9.6%

Map template: http://www.servier.fr/smart/SlideKits/Cartes_géographiques.asp

Diverse sample types

Origin-world wide distribution

Collection date

Origin Disease type

2010 France Gallbladder Cancer, Helicobacter species

2009 Kenya Cervical Cancer (HPV, HIV infections)

2008 Eastern Europe Kidney cancer 2006-7

Russia, Thailand, South East Asia

Lung and kidney cancers; Nasopharyngeal carcinoma; Lymphoma,

2004 Czech Republic, Slovakia Pancreatic cancer

2004

Asia, Iran Esophageal cancer; carcinogen exposure; lifestyle factors

2004 World wide Head and neck cancer

1990s; 2000s World wide HPV, cervical, oral cancers, multicentric study, p53 mutation

1990s; 2000s Low/middle-resource countries

Cervical Cancer, Human papillomavirus

1998 Czech Republic, Poland, Romania, Russia, Hungary, Slovakia

Lung, kidney and UADT cancers

1970s Uganda Burkitt’s lymphoma, Epstein-Barr virus

Biospecimen Usage : INHANCE project Study ID Pooled

studies Projects

GWAS of upper Aero digestive Tract Cancers. (McKay J.D et al., Plos Genet. 2011 Mar;7(3))

2 large European multi-centre case studies

2,091 UADT cancer cases and 3,513 controls and 4,821 generic controls

Recreational physical activity (rPA) and risk of head and neck cancer (Nicolotti N et. al., Eur J Epidemiol. 2011 Aug;26(8): 619-28)

4 Case control studies

2,289 HNC cases and 5,580 controls.

Body mass index and risk of head and neck cancer: (Gaudet MM; Int J Epidemiol 2010 Aug;39(4): 1091-102).

17 case control studies

12, 716 cases; 17438 controls

Sexual behaviours and the risk of head and neck cancers: (Heck JE; Int Epidemiol. 2010 Feb;39(1) :166-81).

4 population-based and 4 hospital-based case-control

5, 642 head and neck cancer cases and 6, 069 controls

The International Head and Neck Cancer Epidemiology (INHANCE) Consortium, established in 2004.

Collaboration of research

groups of large molecular epidemiology studies of HNC world wide

Over 26,000 cases & 34,000 controls-questionnaire data on and biological samples

Biospecimen Science Research: preanalytical variables affecting DNA quality and quantity for GWAS

o Identify preanalytical factors responsible for the variations in DNA purity following extraction.

o High quality of DNA required for GWAS.

Study design DNA extraction from buffy coat from EPIC study Total of 12 projects. Standardized protocol used for in all centres and for DNA extraction at IARC 52 256 samples were extracted over the period; 47 159 DNA’s were analyzed

Variables Age; recruitment site; gender; BMI; cancer status; number of straws used; DNA extraction and quantification methods; heamolysis gradient; time lapse between sample processing steps.

Results Wide variation in DNA yield between centres: ? Due to variation in sample collection techniques. DNA yield decreases with age. Low rate of processing delay: ? Due to protocol harmonization.

Qualification of DNA for GWAS studies

Code-reasons for rejection

1- concentration< 25ng/ul; 2-gender discordant; 3 & 4-poor performance in assay; 5- insufficient volume; 6 - concentration <10 ng/ul; 7-technical issues

International guidelines & standard protocols

Pre analytical sample processing: – DNA extraction – Shipment and transfer of biological material according to

international regulation

IARC’s Green Book ‘Common Minimum Technical Standards and Protocols for biological Resource Centres’

What are the challenges ?

• The my syndrome revisited

• The benefits of sample and data sharing and networking. • create a win-win situation, provide visibility, incentives,

scientific recognition, joint scientific publication.

• Harmonization and standardization. • Data comparability. • Pre analytical processing protocols. • Quality control tools-validation

Challenges cont…

• Sustainability

• Maintenance cost and upkeep of facilities, staff costs. • Appropriate public and institutional support • Efficient and affordable cost recovery program

• Globalization • Under-representation of sample collections from low and

medium income countries

• Legal and social issues relating to material and data access • Clear understanding of local, national and international

regulations. • Feedback mechanism; return of results from researchers to

biobank infrastructures (and participants).

Ethics, consent and access

Initial recruitment

Biological sample collection End-point data

Prospective study -Follow-up and identification of incident cases

2. Ethics clearance required from individual countries and EC’s

3. Individual informed consent

Centalized databases

Centralized biobank

1. Compliance with international and national regulations.

5. Data protection 4. Anonymous data

EPIC steering committee

IARC ethics committee

Expertise in the management

of resources from diverse origin and collaborations.

Experience in pre-analytical sample processing and world wide distribution to/from multiple users with diverse needs.

Opportunities to conduct biospecimen science research.

EUROCAN Platform (WP 10)

EU-FP7 PROLIFICA- study

of liver fibrosis and cancer in Africa

SPIDIA- Evidence-based Quality guidelines for the pre-analytical phase of Blood Samples.

BBMRI- LPC (project proposal submitted)

Strengths and opportunities

International initiatives and collaborations

Thank You

Acknowledgement

IARC biobank team & EPIC-project team