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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 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 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 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)