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Little J, Wilson B, Carter R, et al. Multigene Panels in Prostate Cancer Risk Assessment. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Jul. (Evidence Reports/Technology Assessments, No. 209.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Multigene Panels in Prostate Cancer Risk Assessment.

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Future Research

We identified a number of evaluations of diverse single nucleotide polymorphism (SNP) panels. We could not draw robust conclusions regarding their analytic validity. These studies showed statistically significant associations between combinations of SNPs and risk of prostate cancer. However, when assessed using test evaluation designs, the risk models which incorporated the SNP panels improved the area under the curve only marginally compared with non-SNP-based tests in their ability to distinguish cases from noncases, clinically meaningful from latent or asymptomatic cancer, or in stratifying the prognosis of confirmed cases. These evaluations were not conducted in routine clinical settings. No evidence was identified to address the question of clinical utility.

Future research should focus on evaluating the clinical validity of SNP-based panels more extensively and robustly, in participants more representative of general clinical populations, and compared directly with existing standards of care. In addition to the consideration of discrimination and calibration, it would be helpful to use decision-analysis methods.219 Incorporation of additional SNPs that increase the proportion of the polygenic variance accounted for by measured genetic variants would be expected to increase the absolute difference in risk between extreme tails of the distribution of a SNP panel.244 It has also been observed that adding a polygenic risk score (that is, a score based on SNP alleles associated with disease that do not achieve either nominal statistical significance (p<0.05) or stringent genome-wide statistical significance) does not improve risk prediction for prostate cancer over replicated SNPs from genome-wide association (GWA) studies.245 These observations would suggest a need to identify and validate further genetic markers to enable larger SNP panels to be developed. However, it is also the case that SNPs identified from GWA studies are markers for the region of risk in which the causal SNP is located. The magnitude of risk associated with truly causal variants would be expected to be greater than with the risk markers so far identified. Therefore, the quest to develop future panels useful in risk stratification will depend on further characterization of the regions of genetic risk already identified, as well as possible additional markers. More emphasis needs to be placed on distinguishing aggressive and nonaggressive disease, and investigators should consider the possibility for subgroup analyses at the planning stage of studies.

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