Biobanks of Cerice 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= NOWAC Biopsy cohort Women born n= Questionnaires 30 Years Passive Follow-up – Cancer Registry 5 years Active follow-up through biopsy collection NOWAC Expression cohort n =

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

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