Risk prediction of complex diseases from family history and known susceptibility loci, with applications for cancer screening - PubMed (original) (raw)

Risk prediction of complex diseases from family history and known susceptibility loci, with applications for cancer screening

Hon-Cheong So et al. Am J Hum Genet. 2011.

Abstract

Risk prediction based on genomic profiles has raised a lot of attention recently. However, family history is usually ignored in genetic risk prediction. In this study we proposed a statistical framework for risk prediction given an individual's genotype profile and family history. Genotype information about the relatives can also be incorporated. We allow risk prediction given the current age and follow-up period and consider competing risks of mortality. The framework allows easy extension to any family size and structure. In addition, the predicted risk at any percentile and the risk distribution graphs can be computed analytically. We applied the method to risk prediction for breast and prostate cancers by using known susceptibility loci from genome-wide association studies. For breast cancer, in the population the 10-year risk at age 50 ranged from 1.1% at the 5th percentile to 4.7% at the 95th percentile. If we consider the average 10-year risk at age 50 (2.39%) as the threshold for screening, the screening age ranged from 62 at the 20th percentile to 38 at the 95th percentile (and some never reach the threshold). For women with one affected first-degree relative, the 10-year risks ranged from 2.6% (at the 5th percentile) to 8.1% (at the 95th percentile). For prostate cancer, the corresponding 10-year risks at age 60 varied from 1.8% to 14.9% in the population and from 4.2% to 23.2% in those with an affected first-degree relative. We suggest that for some diseases genetic testing that incorporates family history can stratify people into diverse risk categories and might be useful in targeted prevention and screening.

Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

Plots of Predicted Risks of Breast Cancer in the General Population and in Individuals with a Family History of Disease and with One Affected First-Degree Relative Top: The probability density functions of predicted risks. Middle: The predictiveness curve (predicted risk plotted against the risk percentile). Bottom: the cumulative density functions of predicted risks. The horizontal line in the middle graph represents the average lifetime risk in the whole population. People with an affected first-degree relative are denoted by “Fam Hx +ve.”

Figure 2

Figure 2

Ten-Year Risk of Breast Cancer at Different Risk Percentiles for the General Female Population The horizontal line represents the average 10-year risk of breast cancer for a 50-year-old woman.

Figure 3

Figure 3

Ten-Year Risk of Breast Cancer at Different Risk Percentiles for Women with One Affected First-Degree Relative The horizontal line represents the average 10-year risk of breast cancer for a 50-year-old woman.

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