CD38 Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians

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 rs64...

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Published in:	Cancer epidemiology, biomarkers & prevention Vol. 18; no. 3; pp. 945 - 953
Main Authors:	JAMROZIAK, Krzysztof, SZEMRAJ, Zofia, KOSTYRA, Aleksandra, CALBECKA, Malgorzata, WAWRZYNIAK, Ewa, MIROWSKI, Marek, KORDEK, Radzislaw, ROBAK, Tadeusz, GRZYBOWSKA-IZYDORCZYK, Olga, SZEMRAJ, Janusz, BIENIASZ, Magdalena, CEBULA, Barbara, GIANNOPULOS, Krzysztof, BALCERCZAK, Ewa, JESIONEK-KUPNICKA, Dorota, KOWAL, Malgorzata
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-03-2009
Subjects:	ADP-ribosyl Cyclase 1 - genetics Alleles Biological and medical sciences Case-Control Studies CD38 Chi-Square Distribution chronic lymphocytic leukemia European Continental Ancestry Group Gene Expression Genetic Predisposition to Disease genetic susceptibility Genotype Hematologic and hematopoietic diseases Humans Leukemia, Lymphocytic, Chronic, B-Cell - ethnology Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Linkage Disequilibrium Logistic Models Medical sciences Poland Polymerase Chain Reaction polymorphism Polymorphism, Single Nucleotide SNP Statistics, Nonparametric Tumors Poland Europe Human Genetic variability Genotype B cell neoplasm Malignant hemopathy B-Lymphocyte Case control study Epidemiology Chronic lymphocytic leukemia Cancerology Lymphoproliferative syndrome Risk factor Predisposition Genetics Caucasoid Public health Cancer Polymorphism
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Summary:	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, Arg 140 Trp) 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. (Cancer Epidemiol Biomarkers Prev 2009;18(3):945–53)
ISSN:	1055-9965 1538-7755
DOI:	10.1158/1055-9965.EPI-08-0683