title: Genetic variation in CXCR4 and risk of chronic lymphocytic leukemia.
abstract: A genome-wide linkage scan has provided evidence for a chronic lymphocytic leukemia (CLL) susceptibility locus at 2q21 to which the chemokine receptor CXCR4 gene maps. Recent data provide some evidence for common variation in CXCR4 according to the polymorphic variant rs2228014 defining CLL risk. To examine the role of genetic variation in CXCR4 on CLL risk, we screened 188 familial CLL cases and 213 controls for germline mutations in the coding regions of CXCR4 and genotyped rs2228014 in 1058 CLL cases and 1807 controls. No association between rs2228014 and risk of CLL was seen (P = .83). One truncating (W195X) and 2 missense mutations with possible functional consequences (V139I and G335S) were identified among 186 familial cases and 0 in 213 controls sequenced. Our analysis provides no evidence that common variation in CXCR4 defined by rs228014 influences the risk of CLL, but that functional coding mutations in CXCR4 may contribute to familial CLL.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, United Kingdom.
authors.forename: Dalemari
authors.initials: D
authors.lastname: Crowther-Swanepoel
authors.forename: Mobshra
authors.initials: M
authors.lastname: Qureshi
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Claire
authors.initials: C
authors.lastname: Dearden
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology* / Q000235:genetics; D020125:Mutation, Missense; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000502:physiology; D012306:Risk
chemical_list: C527276:CXCR4 protein, human; D018389:Codon, Nonsense; D019718:Receptors, CXCR4