Transcript DG-041 Single Dose Results

Genetic Risk Tests for early detection of
Prostate Cancer
Jeff Gulcher MD PhD
Chief Scientific Officer and co-Founder
Decode Genetics
Prostate cancer detection
 27,000 men died in 2007, African-Americans at higher risk
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for cancer and for death due to cancer
(15 years ago – 40,000 deaths per year before PSA used )
Best treatment is early detection
We have tools for curative treatment if detected early
More emphasis needs to be made on early detection vs
late treatment
The only major risk factors are ethnicity and family history
of early prostate cancer (younger than 65)
Need new ways to focus PSA and diagnostic procedures
to those who are highest risk
Prostate cancer genetic risk markers
– discovery and wide replication
 Discovery in white populations – 2500 patients vs 20,000
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controls using 300,000 markers
All 8 markers replicated in 4000 to 12,000 white patients and
30,000 white controls
4 of these markers have been replicated in smaller numbers
African-American patients (small collections of 150 to 500)
The remaining markers may not adequately tested in small
numbers of patients – may need to recruit more participants in
these important studies
In some cases the markers which are more important to AfricanAmericans are different but near the ones first found in whites
In other cases, the strongest markers for whites are not
important for African-Americans and vice versa (example- the
9p21 heart attack markers do not impact AA risk)
Prostate cancer genetic risk test
(deCODE ProstateCancer)
 Measures 8 SNP markers over 6 regions originally
discovered by Decode and confirmed in numerous
populations – covers 70% of the genetic risk
 The genetic risk profile ranges from 0.4 to over 6 fold
 10% of the white population is at 2 fold risk (33% lifetime
risk), 1% has 3 fold risk (49% lifetime risk)
 This is a risk test – not determinative
 Defines patients more likely to have more aggressive
cancer
 The risk profile is independent of risk due to family history
Case Study in the use of deCODE Prostate Cancer
 48 year old white male in good apparent health,
 father diagnosed with localized prostate cancer at age 68
 ACS guidelines recommend screening with PSA beginning at
age 50 unless family history of early prostate cancer < 65
 deCODE Prostate Cancer results:
 Relative risk = 1.88 fold compared to general population risk
for white males.
 Calculated lifetime risk = 1.88 X 16% = 30%
 Modestly higher risk for aggressive vs. non-aggressive disease
Case Study in the use of deCODE Prostate Cancer
 High risk prompted early PSA test by primary care
 PSA – midrange normal at 2.0ng/ml
 High risk prompted urologist to perform TRUS-guided biopsy
 Positive in 3 out of 12 core biopsies – 15% volume
 Gleason score of 6 (3/3) – intermediate grade
 Negative workup for cancer spread
 Radical prostatectomy with nerve sparing for likely cure
 Final pathology on resected prostate showed Gleason 7 (highgrade) in both lobes
 Followup PSA now 0.0 (presumed cure)
Risk & Family History
5%
High Risk
15% High Risk
account for 30%
of prostate cancers
Family History
Alone
deCODE ProstateCancer
95%
Average
Risk
&
Family History
Prostate cancer
– early detection needs for African-Americans
 Need larger collections of patients and controls
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 To ensure rapid translation of discoveries made in large
studies in white to African-Americans, who are at even higher
overall risk
 Need to use in African-Americans the industrial-scale genetic
approaches that have worked so well in whites
Solutions:
 Collaborate with patient organizations like PHEN and NMA to
recruit more participants
 Continue and expand funding for collections of patients and
controls by medical centers
 Combine the numerous projects at NIH and funded by NIH
 Do not cut the SCOR grant program which funds collections
 Begin to fund genome-wide association discovery projects for
African-Americans (does not exist because large numbers of
patients have not been collected – Catch-22)