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The search for low-penetrance cancer susceptibility alleles

Oncogene volume 23, pages 6471–6476 (2004)Cite this article

Abstract

Much of the familial aggregation of common cancer results from inherited susceptibility, but highly penetrant mutations in known genes cannot account for most of the excess. Some of the unexplained familial risk is presumably due to high-penetrance mutations in as yet unidentified genes, but polygenic mechanisms are likely to account for a greater proportion, particularly in breast cancer. This inference, coupled with technological developments, has led to a renaissance in association studies. Most such studies have evaluated small numbers of single-nucleotide polymorphisms (SNPs) in a few candidate genes, but reliable high-density oligonucleotide arrays and other novel techniques will allow genome-wide allelic association studies to be conducted. High-density genome-wide SNP analysis will include targets identified by structural considerations, as well as the growing list of candidate genes. In the longer term, high-throughput re-sequencing will be required to identify the rare pathogenic variants that may constitute the majority of low-penetrance alleles. The detection of low-penetrance cancer susceptibility genes will then be restricted mainly by the availability of large numbers of well-characterized cases and controls. Cancer patients with affected relatives are considerably more informative than unselected cases for such studies.

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Authors and Affiliations

  1. Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, Surrey, UK

    Richard S Houlston

  2. London School of Hygiene and Tropical Medicine, Keppel St, London, WC1E 7HT, UK

    Julian Peto

  3. Cancer Research UK Epidemiology and Genetics Unit, Institute of Cancer Research, Sutton, SMZ 5NG, Surrey, UK

    Julian Peto

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  2. Julian Peto
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Correspondence to Richard S Houlston or Julian Peto.

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Houlston, R., Peto, J. The search for low-penetrance cancer susceptibility alleles. Oncogene 23, 6471–6476 (2004). https://doi.org/10.1038/sj.onc.1207951

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