Multigeneration epidemiology using biobanks

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Multigeneration epidemiology using biobanks

• Kari Hemminki
• German Cancer Research Center, Karolinska
  Institute

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Multigeneration epidemiology
Aim genetic basis of disease

• Classical approach collect samples fromfamilial
  cases (testing for known syndromes, BRCA1/2)
• Novel approach registers and biobanks
• At onset evidence on heritability, familial
  risk?!

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Logistics

• Data on disease in families

• Biobanks

• tumor samples
• cervical smears
• maternity cohorts
• neonatal screening
• ad hoc biobanks

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Family-Cancer Database, 2004

• Offspring born in Sweden 1932-02 with their
  parents
• Persons 10.6 million
  (3.5 million families)
• Cancer cases
  0.9 million
• Cancer in situ cases 0.2
  million

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Family-Cancer Database on the time axis
Registration of cancer cases
Offspring born
Parents born
1900
1932
1958
1998
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Familial SIRs
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SIR for concordant cancer in offspring and spouses
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SIR for cancer in siblings by age difference
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SIR for cancer in siblings of parental and
sibling probands
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SIRs, familial proportions and PAFs for parental
history
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Familial risks and known cancer genes
Cancer site
RISK
GENES
PROPORTION

Colorectum
1.95
Mismatch repair APC, LKB, MYH, BLM
30
Lung
1.83
Metabolic low-penetrance genes
?
30
Breast
1.67
BRCA1/2, ATM
CHEK2

Corpus uteri
2.57
Mismatch repair, PTEN
20 ?
Ovary
3.01
BRCA1/2, mismatch repair
30-50
Prostate
2.35
Candidate loci
0

Bladder
1.66
Metabolic low-penetrance genes
?
Melanoma
2.43
CDKN2A
10 ?


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High-risk cancers in FCD(genes known)
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High-risk cancers in FCD(genes unknown)
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Familiar risks in Sweden(siblings)
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Tumor samples

• Available on most recent cancers
• Distributed all over country (Sweden 60
  hospitals)
• PCR amplification OK after 1980
• Collection rate 70, for pair 49
• Tumor normal tissue, useful for many purposes

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Other tissue samples
Cervical smears, recent decades, middle age
women, amount DNA?

• Maternity cohortsFinland since 1983, oldest
  women in cancer age
• Neonatal screeningSweden guthrie cards from
  1980s
• Ad hoc collections ...

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Perspectives

• Classical approach is preferred, if feasible

• Novel register/biobank approach may be useful
  to
• confirm
• provide new hypothesis
• Novel approach works best if the aims are clear