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

• 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
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0683

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)