Common variants in the gene SMAD7 are associated with an increased risk of colorectal cancer, reports a study to be published online in Nature Genetics.
Richard Houlston, Ian Tomlinson and colleagues carried out a genome-wide association study, genotyping more than 500,000 single nucleotide polymorphisms (SNPs) in several thousand individuals with familial colorectal cancer, as well as controls.
Three SNPs in SMAD7 were associated with increased risk of the disease in an initial sample, as well as in three replication sample sets, with a high degree of statistical significance. SMAD7 is an intracellular molecule that inhibits the TGF-beta pathway, which is involved in cell-cell signalling events in a wide range of tissues, including the colon. Although variation in SMAD7 contributes only modestly to risk of colorectal cancer -- it contributes to approximately 15% of such cancers in the general population, and less than 1% of the familial risk -- this result suggests, together with other recent data, that common variants of modest effect underlying this disease exist and can be discovered.
Richard Houlston (Institute of Cancer Research, Sutton, UK)
Ian Tomlinson (Cancer Research UK, London)
Abstract available online.
(C) Nature Genetics press release.
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