Houlston, R. S., Peto, J. (2004) The search for low-penetrance cancer susceptibility alleles. ONCOGENE, 23 (38). pp. 6471-6476. ISSN 0950-9232

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Abstract

The search for low-penetrance cancer susceptibility alleles 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 resequencing 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.

Item Type:	Review Article
Authors (ICR Faculty only):	Peto, Julian and Houlston, Richard
All Authors:	Houlston, R. S., Peto, J.
Uncontrolled Keywords:	low-penetrance genes; cancer; risk Complex human-diseases; breast-cancer; linkage disequilibrium; lung-cancer; brca2 mutations; risk; association; polymorphisms; gene; localization
Research teams:	Closed research groups > Cancer Research UK Epidemiology & Genetics Unit ICR divisions > Genetics and Epidemiology > Molecular & Population Genetics ICR divisions > Molecular Pathology > Molecular & Population Genetics
Date Deposited:	10 Aug 2007 21:04
Last Modified:	10 Feb 2010 11:48
URI:	http://publications.icr.ac.uk/id/eprint/3762

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