1. ¹Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK
2. ²Department of Cellular Pathology, St George's Hospital, London, SW17 0QT, UK
3. ³Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
4. ⁴Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, UK
5. ⁵Institute of Cancer Research, Surrey, UK

Correspondence: R Houlston, Section of Cancer Research, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. E-mail: Richard.houlston@icr.ac.uk

Received 2 May 2007; Revised 24 August 2007; Accepted 29 August 2007; Published online 25 September 2007.

Abstract

Approximately, a third of all colorectal cancer (CRC) is due to inherited susceptibility. However, high-risk mutations in APC, the mismatch repair (MMR) genes, MUTYH/MYH, SMAD4, ALK3 and STK11/LKB1 are rare and account for <5% of cases. Much of the remaining variation in genetic risk is likely to be explained by combinations of more common gene variants that modestly increase risk. Reliable identification of such 'low penetrance' alleles would provide insight into the aetiology of CRC and might highlight potential therapeutic and preventative interventions. In 2003, the National Study of Colorectal Cancer Genetics (NSCCG) was established with the aim of collecting DNA and clinicopathological data from 20 000 CRC cases and a series of spouse/partner controls, thereby creating a unique resource for identifying low-penetrance CRC susceptibility alleles. The National Cancer Research Network (NCRN) adopted NSCCG onto its portfolio of trials and 148 centres in the United Kingdom (UK) are now actively participating. Over 8700 cases and 2185 controls have so far been entered into NSCCG. Our experience in developing NSCCG serves to illustrate how world-class DNA databases for genetic analyses can be rapidly developed in the United Kingdom.