RESEARCH Open Access Telethon Network of Genetic Biobanks ...
Biobanks of Cerice Center for Gene Expression Research in Cancer Epidemiology Eiliv Lund, UiTø.
-
Upload
lindsay-carr -
Category
Documents
-
view
215 -
download
0
Transcript of 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=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
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