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. 2011 May 10;104(10):1656-63.
doi: 10.1038/bjc.2011.118. Epub 2011 Apr 5.

Polygenic susceptibility to prostate and breast cancer: implications for personalised screening

N Pashayan  1 , S W Duffy, S Chowdhury, T Dent, H Burton, D E Neal, D F Easton, R Eeles, P Pharoah
Affiliations

Polygenic susceptibility to prostate and breast cancer: implications for personalised screening

N Pashayan et al. Br J Cancer. .

Abstract

Background: We modelled the efficiency of a personalised approach to screening for prostate and breast cancer based on age and polygenic risk-profile compared with the standard approach based on age alone.

Methods: We compared the number of cases potentially detectable by screening in a population undergoing personalised screening with a population undergoing screening based on age alone. Polygenic disease risk was assumed to have a log-normal relative risk distribution predicted for the currently known prostate or breast cancer susceptibility variants (N=31 and N=18, respectively).

Results: Compared with screening men based on age alone (aged 55-79: 10-year absolute risk ≥2%), personalised screening of men age 45-79 at the same risk threshold would result in 16% fewer men being eligible for screening at a cost of 3% fewer screen-detectable cases, but with added benefit of detecting additional cases in younger men at high risk. Similarly, compared with screening women based on age alone (aged 47-79: 10-year absolute risk ≥2.5%), personalised screening of women age 35-79 at the same risk threshold would result in 24% fewer women being eligible for screening at a cost of 14% fewer screen-detectable cases.

Conclusion: Personalised screening approach could improve the efficiency of screening programmes. This has potential implications on informing public health policy on cancer screening.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Ten-year absolute risk of being diagnosed with prostate or breast cancer, England, 2002–2006.
Figure 2
Figure 2
Men eligible for screening and cases detectable by screening at different risk thresholds. Percentage of men 45–79 years of age with polygenic risk for prostate cancer greater than a given threshold risk and percentage of men with detectable prostate cancer within this high-risk population, England, 2002–2006.
Figure 3
Figure 3
Change in proportion of individuals eligible for screening with increase in the known susceptibility variants. The likely percentage fewer individuals that would be eligible for screening under the personalised screening strategy as compared with the standard screening while detecting the same number of cases with increase in the percentage of the known susceptibility alleles. Prostate: compared with screening men 55–79; currently ∼24% of the variants known. Breast: compared with screening women 47–79; currently ∼9% of the variants known.
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