AmbryScore for Prostate Cancer

Learn more about your patient’s prostate cancer risk by opting into AmbryScore.

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What is AmbryScore for Prostate Cancer?

AmbryScore is a polygenic risk score (PRS) designed to estimate a man’s individualized risk for prostate cancer using genetic information. The test can be added to select multigene panels and provides a prostate cancer risk assessment based on the combined effects of 72 single nucleotide polymorphisms (SNPs), which have been previously associated with prostate cancer risk.1-10

Why is this important?

  • AmbryScore provides additional prostate cancer risk information for men who test negative for a mutation in a prostate cancer susceptibility gene to better guide medical management
  • Men with an increased risk for prostate cancer may need to consider earlier and/or more frequent surveillance for early detection
  • For men with a previous prostate cancer diagnosis, an elevated PRS may be one contributing factor to help explain disease development

Who is eligible for AmbryScore for Prostate Cancer?

Patients must meet all of the following criteria:

  1. Male biological sex
  2. 18-84 years old
  3. Northern European ancestry
  4. No personal or family history of a mutation in a prostate cancer susceptibility gene*

* ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, TP53

AmbryScore for prostate cancer can be added to any of the following multigene panels,
but is not available as a standalone test:

Test Description

The AmbryScore tool for prostate cancer provides a personalized estimate of prostate cancer risk based on the following patient-specific factors: age at testing, ethnicity, and results of SNP profiling. A population standardized PRS is computed as the sum of the patient’s risk alleles across 72 SNPs, weighted by the SNP-specific effects reported in large prostate cancer studies, and ethnicity-specific allele frequencies11,12. The AmbryScore calculation is highly dependent on the accuracy of clinician-provided data. Other factors not accounted for in the AmbryScore calculation may impact prostate cancer risk including, but not limited to, germline mutations not analyzed by the ordered genetic test. The AmbryScore provided is patient-specific and cannot be used to infer risk to relatives.

Sequencing of the SNPs is carried out by a bait-capture methodology using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and Next-Generation sequencing. A PRS score is generated when genotype data is available for at least 65/72 (≥90%) analyzed SNPs.

Remaining Lifetime Prostate Cancer Risk by Age (General Population, Non-Hispanic White)13

Age (years) Non-Hispanic White, Male only
SEER Prostate Cancer-specific lifetime risk to age 85 (%)
10 9.91
15 9.92
20 9.95
25 10.00
30 10.07
35 10.15
40 10.24
45 10.34
50 10.38
55 10.20
60 9.60
65 8.40
70 6.36
75 4.07
80 1.95

References

  1. Thomas, G., et al., Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet, 2008. 40(3): p. 310-5.
  2. Yeager, M., et al., Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet, 2007. 39(5): p. 645-9.
  3. Gudmundsson, J., et al., Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat Genet, 2008. 40(3): p. 281-3.
  4. Al Olama, A.A., et al., Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat Genet, 2009. 41(10): p. 1058-60.
  5. Eeles, R.A., et al., Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet, 2009. 41(10): p. 1116-21.
  6. Kote-Jarai, Z., et al., Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat Genet, 2011. 43(8): p. 785-91.
  7. Schumacher, F.R., et al., Genome-wide association study identifies new prostate cancer susceptibility loci. Hum Mol Genet, 2011. 20(19): p. 3867-75.
  8. Eeles, R.A., et al., Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet, 2013. 45(4): p. 385-91, 391e1-2.
  9. Al Olama, A.A., et al., A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet, 2014. 46(10): p. 1103-9.
  10. Hoffmann, T.J., et al., 2016. A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences. Cancer Discov, 2015. 5(8): p. 878-91.
  11. Conran CA et al., Population standardized genetic risk score: the SNP based method of choice for inherited risk assessment of prostate cancer. Asian Journal of Andrology 2016; 18: 520–524.
  12. Chen H, et al., Adding Genetic Risk Score to Family History Identifies Twice as Many High-risk Men for Prostate Cancer: Results from The Prostate Cancer Prevention Trial. Prostate 2016; 76(12): 1120–1129.
  13. Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database released April 2018 (www.seer.cancer.gov).

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