title: Inherited genetic susceptibility to monoclonal B-cell lymphocytosis.
abstract: Monoclonal B-cell lymphocytosis (MBL) is detectable in > 3% of the general population. Recent data are compatible, at least in a proportion of cases, with MBL being a progenitor lesion for chronic lymphocytic leukemia (CLL) and a surrogate for inherited predisposition. Common single nucleotide polymorphisms (SNPs) at 2q13 (rs17483466), 2q37.1 (rs13397985), 2q37.3 (rs757978), 6p25.3 (rs872071), 8q24.21 (rs2456449), 11q24.1 (rs735665), 15q21.3 (rs7169431), 15q23 (rs7176508), 16q24.1 (rs305061), and 19q13.32 (rs11083846) have been shown to confer a modest but significant increase in CLL risk. To examine the impact of these 10 SNPs on MBL, we analyzed 3 case-control series totaling 419 cases and 1753 controls. An association between genotype and MBL risk was seen for 9 SNPs, 6 of which were statistically significant: rs17483466 (odds ratio [OR] =1.27; P = .02), rs13397985 (OR = 1.40; P = 1.72 × 10(-3)), rs757978 (OR = 1.38; P = .02), rs872071 (OR = 1.27; P = 7.75 × 10(-3)), rs2456449 (OR = 1.31; P = 3.14 × 10(-3)), and rs735665 (OR = 1.63; P = 6.86 × 10(-6)). Collectively, these data provide support for genetic variation influencing CLL risk through predisposition to MBL.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Dalemari
authors.initials: D
authors.lastname: Crowther-Swanepoel
authors.forename: Tanguy
authors.initials: T
authors.lastname: Corre
authors.forename: Amy
authors.initials: A
authors.lastname: Lloyd
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.forename: Bianca
authors.initials: B
authors.lastname: Olver
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Bennett
authors.forename: Chi
authors.initials: C
authors.lastname: Doughty
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
authors.forename: Federico
authors.initials: F
authors.lastname: Calligaris-Cappio
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008218:Lymphocytosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*