title: CD38 gene polymorphisms contribute to genetic susceptibility to B-cell chronic lymphocytic leukemia: evidence from two case-control studies in Polish Caucasians.
abstract: Given the recent findings on the importance of CD38 signaling in the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), we hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to B-CLL risk. We evaluated two potentially functional CD38 SNPs, intronic rs6449182 (184C>G) and missense rs1800561 (418C>T, Arg140Trp) in two hospital-based case-control studies (study A and validation study B). Genotyping was done using PCR-based assays in a total of 460 Polish Caucasian patients with B-CLL and 503 age-matched and gender-matched controls. We found that frequencies of both variant alleles (rs6449182 G and rs1800561 T) were significantly higher in B-CLL. In study A, logistic regression analysis revealed an association between B-CLL and genotypes: rs6449182 CG [odds ratio (OR), 3.57; 95% confidence interval (95% CI), 2.4-5.3], rs6449182 GG (OR, 5.2; 95% CI, 2.36-11.5), and rs1800561 CT (OR, 6.72; 95% CI, 1.5-30.1), although no homozygous rs1800561 TT genotype was detected in either study. These results were confirmed in study B, which showed an association between B-CLL and genotypes rs6449182 CG (OR, 4.00; 95% CI, 2.7-6.0), rs6449182 GG (OR, 12.84; 95% CI, 4.3-38.7), and rs1800561 CT (OR, 10.12; 95% CI, 1.3-81.6), and in the combined analysis of both studies. We also observed that rs6449182 G carriers had more advanced clinical stage (P=0.002) and tended to be younger at diagnosis (P=0.056). Furthermore, we found higher CD38 transcript levels and higher proportions of CD38-positive cells in carriers of rs6449182 G and rs1800561 T alleles (P<0.05 for all comparisons). In conclusion, our data show that CD38 SNPs may affect CD38 expression and contribute to the increased risk of B-CLL carcinogenesis.
authors.affiliation: Department of Hematology, Medical University of Lodz, Ciolkowskiego 2, 93-513 Lodz, Poland. krzysztof.jamroziak@wp.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jamroziak
authors.forename: Zofia
authors.initials: Z
authors.lastname: Szemraj
authors.forename: Olga
authors.initials: O
authors.lastname: Grzybowska-Izydorczyk
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bieniasz
authors.forename: Barbara
authors.initials: B
authors.lastname: Cebula
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
authors.forename: Ewa
authors.initials: E
authors.lastname: Balcerczak
authors.forename: Dorota
authors.initials: D
authors.lastname: Jesionek-Kupnicka
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kowal
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kostyra
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Calbecka
authors.forename: Ewa
authors.initials: E
authors.lastname: Wawrzyniak
authors.forename: Marek
authors.initials: M
authors.lastname: Mirowski
authors.forename: Radzislaw
authors.initials: R
authors.lastname: Kordek
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D011044:Poland; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D044465:White People
chemical_list: D051997:ADP-ribosyl Cyclase 1