title: Lack of a relationship between the common 18q24 variant rs12953717 and risk of chronic lymphocytic leukemia.
abstract: Linkage has implicated variation in 18q24 in genetic susceptibility to chronic lymphocytic leukemia (CLL). 18q24 harbors mothers against decapentaplegic homolog 7 (SMAD7), an intracellular antagonist of TGF-beta signaling which participates in a negative feedback loop controlling growth arrest and apoptosis of B-cells. Recently we have demonstrated variation in SMAD7, defined by the single nucleotide polymorphism rs12953717, to be strongly associated with risk of colorectal cancer. Given that many polymorphic variants have pleiotropic effects we explore the relationship between polymorphic variation at rs12953717 and CLL we compared the frequency of genotypes in 984 cases and 4831 healthy controls. There was therefore no evidence for an association between rs12953717 genotype and CLL; P = 0.40 (allelic test) with ORs of 0.99 (95% CI: 0.85 - 1.16) and 0.91 (95% CI: 0.74 - 1.11) for heterozygotes and TT homozygotes, respectively. These data suggests variation at SMAD7 does not significantly contribute to an inherited susceptibility to CLL.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sellick
authors.forename: Sarah
authors.initials: S
authors.lastname: Fielding
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
mesh_terms: D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051906:Smad7 Protein / Q000235:genetics*
chemical_list: C497806:SMAD7 protein, human; D051906:Smad7 Protein