IARC Biobank
Maimuna MENDY [email protected]
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