Inherited genetic susceptibility to monoclonal B-cell lymphocytosis.
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.
Crowther-Swanepoel
Dalemari
D
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Corre
Tanguy
T
Lloyd
Amy
A
Gaidano
Gianluca
G
Olver
Bianca
B
Bennett
Fiona L
FL
Doughty
Chi
C
Toniolo
Daniela
D
Caligaris-Cappio
Federico
F
Calligaris-Cappio
Federico
F
Ghia
Paolo
P
Rossi
Davide
D
Rawstron
Andy C
AC
Catovsky
Daniel
D
Houlston
Richard S
RS
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*