Biobanks ofCerice

Center for Gene Expression Research in Cancer

Epidemiology

Eiliv Lund, UiTø

• How should the description of the genome change epidemiological design if this was to be a change of paradigm for medical research?

Functional genomics

• Two major components

• Determining the sequence of the genome

• Patterns of gene expression

Cohort studies

Information content in cohort studies

- questionnaire (interview) information

- biomarkers (plasma, serum, urin etc) – proteom/metabolom

- DNA for SNPs analysis (buffy coat, full blood)

- Eventually parafin blocks for tumor DNA

Present situation for the traditional cohort design

• Huge amount of cohort fullfilling most of the criteria

• EPIC – European Prospective Investigation into Nutrition and Cancer

• Consortium of cohorts (NCI)

• New cohorts – Estonian, Biobank UK, the Last cohort etc

The Norwegian Women and Cancer postgenome cohort study

• The intention was to add two new biobanks:

• 1. A prospective collection of blood for expression analysis, whole genome microarray analysis

• 2. Tumor samples from breast cancer cases arising in the cohort preserved for expression analysis

NOWAC all women, n=170 000

NOWAC Biopsy cohortWomen born 1943-57n=147 000

Questionnaires

30 Years

Passive Follow-up – Cancer Registry

5 years

Active follow-up throughbiopsy collection

NOWAC Expression cohort n = 40 000

3 new designs

• How to integrate expression analysis into standard prospective design

• Why

1. Prospective expression analysis

• Fingerprints of exposure

• Metabolic pathways

• Early diagnostic markers

# genes=161642 sample t-test Significant genes, BAM

p<0.01HRT vs. no HRT 61 3

Cod-liver oil + capsels vs. no cod-liver oil 622 219Cod-liver oil vs. no Cod-liver oil 243 0

Cod-liver oil in capsels vs. no cod-liver oil 417 5

1. Prospective expression analysis

• Fingerprints of exposure

• Metabolic pathways

• Early diagnostic markers

2. Case-control upon a cohort design

• Information collected as a case-control study at time of diagnosis AND the same information at start of follow-up

• Intra-individual gene expression analysis

• Repeated information

3. Prospective changes of gene expression in peripheral blood cells in relation to expression profiles of breast

cancer tissue

• Case-case design for breast cancer cases comparing expression patterns over time in relation to tumour expression, eventually stratified on genotype, adjusting for lifestyle exposure like hormones etc.

Biopsy project

• Inclusion criteria born 1943-57• Collaboration with the nationwide research group

Norwegian Breast Cancer Group, NBCG• Breast cancer only treated at public hospitals• Excluding hospitals with less than 20 cases per

year, or 9% of total case load. Increasing centralisation due to mammographic screening programme leaves us with about 20 hospitals

Statistical power

• Expression cohort: 40 000 women gives approximately 120 breast cancer cases each year (incidence rate 300/100 000 per year). Inclusion rate unknown – estimated to 60% – follow-up time 5 years, funded by NFR 2005-07

• Biopsy cohort: 150 000 women gives approximately 450 breast cancer cases per year

Design and statistical power

• Change from indirect to direct design reduces the sample size till ¼ - ½

Conclusion• The NOWAC postgenome cohort need to add

new designs for incorporation of expression analysis of peripheral blood and tumour tissue in standard prospective studies

• The collection of the first biobank of buffered RNA for prospectively use will be completed winter 2006

• The adding of a tumour tissue bank for breast cancer will start winter 2006

• Thanks to A-L Børresen Dale for enthusiastic collaboration