1. ¹Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK
2. ²Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK

Correspondence: Dr RS Houlston, E-mail: richard.houlston@icr.ac.uk

³These authors contributed equally to this work

Received 13 December 2007; Revised 16 February 2008; Accepted 27 February 2008; Published online 25 March 2008.

Abstract

Polymorphisms in CASP8 at 2q33.1 have been associated with the risk of developing cancer, specifically, the D302H variant (rs1045485) with breast cancer in the European population and the -652 6N ins/del promoter variant (rs3834129) with multiple tumours including colorectal cancer (CRC) in the Chinese population. We evaluated the relationship between -652 6N ins/del and D302H variants and risk of developing CRC in the UK population by genotyping 4016 cases and 3749 controls. Both variants showed no evidence of an association with risk of developing CRC (P=0.42 and 0.22, respectively). In contrast, the recently identified CRC susceptibility allele rs6983267 mapping to 8q24 was significantly associated with disease risk (P=8.94 10^-8). It is thus very unlikely that variation in CASP8 defined by -652 6N ins/del or D302H influences the risk of CRC in European populations. The implications of our findings both in terms of population-specific effects and publication bias are discussed.