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CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians
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| Zeitschriftentitel: | Cancer Epidemiology, Biomarkers & Prevention |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , |
| In: | Cancer Epidemiology, Biomarkers & Prevention, 18, 2009, 3, S. 945-953 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Jamroziak, Krzysztof Szemraj, Zofia Grzybowska-Izydorczyk, Olga Szemraj, Janusz Bieniasz, Magdalena Cebula, Barbara Giannopoulos, Krzysztof Balcerczak, Ewa Jesionek-Kupnicka, Dorota Kowal, Malgorzata Kostyra, Aleksandra Calbecka, Malgorzata Wawrzyniak, Ewa Mirowski, Marek Kordek, Radzislaw Robak, Tadeusz Jamroziak, Krzysztof Szemraj, Zofia Grzybowska-Izydorczyk, Olga Szemraj, Janusz Bieniasz, Magdalena Cebula, Barbara Giannopoulos, Krzysztof Balcerczak, Ewa Jesionek-Kupnicka, Dorota Kowal, Malgorzata Kostyra, Aleksandra Calbecka, Malgorzata Wawrzyniak, Ewa Mirowski, Marek Kordek, Radzislaw Robak, Tadeusz |
|---|---|
| author |
Jamroziak, Krzysztof Szemraj, Zofia Grzybowska-Izydorczyk, Olga Szemraj, Janusz Bieniasz, Magdalena Cebula, Barbara Giannopoulos, Krzysztof Balcerczak, Ewa Jesionek-Kupnicka, Dorota Kowal, Malgorzata Kostyra, Aleksandra Calbecka, Malgorzata Wawrzyniak, Ewa Mirowski, Marek Kordek, Radzislaw Robak, Tadeusz |
| spellingShingle |
Jamroziak, Krzysztof Szemraj, Zofia Grzybowska-Izydorczyk, Olga Szemraj, Janusz Bieniasz, Magdalena Cebula, Barbara Giannopoulos, Krzysztof Balcerczak, Ewa Jesionek-Kupnicka, Dorota Kowal, Malgorzata Kostyra, Aleksandra Calbecka, Malgorzata Wawrzyniak, Ewa Mirowski, Marek Kordek, Radzislaw Robak, Tadeusz Cancer Epidemiology, Biomarkers & Prevention CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians Oncology Epidemiology |
| author_sort |
jamroziak, krzysztof |
| spelling |
Jamroziak, Krzysztof Szemraj, Zofia Grzybowska-Izydorczyk, Olga Szemraj, Janusz Bieniasz, Magdalena Cebula, Barbara Giannopoulos, Krzysztof Balcerczak, Ewa Jesionek-Kupnicka, Dorota Kowal, Malgorzata Kostyra, Aleksandra Calbecka, Malgorzata Wawrzyniak, Ewa Mirowski, Marek Kordek, Radzislaw Robak, Tadeusz 1055-9965 1538-7755 American Association for Cancer Research (AACR) Oncology Epidemiology http://dx.doi.org/10.1158/1055-9965.epi-08-0683 <jats:title>Abstract</jats:title><jats:p>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&gt;G) and missense rs1800561 (418C&gt;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 &lt; 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)</jats:p> <i>CD38</i>Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians Cancer Epidemiology, Biomarkers & Prevention |
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| title |
CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_unstemmed |
CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_full |
CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_fullStr |
CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_full_unstemmed |
CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_short |
CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_sort |
<i>cd38</i>gene polymorphisms contribute to genetic susceptibility to b-cell chronic lymphocytic leukemia: evidence from two case-control studies in polish caucasians |
| topic |
Oncology Epidemiology |
| url |
http://dx.doi.org/10.1158/1055-9965.epi-08-0683 |
| publishDate |
2009 |
| physical |
945-953 |
| description |
<jats:title>Abstract</jats:title><jats:p>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&gt;G) and missense rs1800561 (418C&gt;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 &lt; 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)</jats:p> |
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| author_facet | Jamroziak, Krzysztof, Szemraj, Zofia, Grzybowska-Izydorczyk, Olga, Szemraj, Janusz, Bieniasz, Magdalena, Cebula, Barbara, Giannopoulos, Krzysztof, Balcerczak, Ewa, Jesionek-Kupnicka, Dorota, Kowal, Malgorzata, Kostyra, Aleksandra, Calbecka, Malgorzata, Wawrzyniak, Ewa, Mirowski, Marek, Kordek, Radzislaw, Robak, Tadeusz, Jamroziak, Krzysztof, Szemraj, Zofia, Grzybowska-Izydorczyk, Olga, Szemraj, Janusz, Bieniasz, Magdalena, Cebula, Barbara, Giannopoulos, Krzysztof, Balcerczak, Ewa, Jesionek-Kupnicka, Dorota, Kowal, Malgorzata, Kostyra, Aleksandra, Calbecka, Malgorzata, Wawrzyniak, Ewa, Mirowski, Marek, Kordek, Radzislaw, Robak, Tadeusz |
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| description | <jats:title>Abstract</jats:title><jats:p>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&gt;G) and missense rs1800561 (418C&gt;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 &lt; 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)</jats:p> |
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| spelling | Jamroziak, Krzysztof Szemraj, Zofia Grzybowska-Izydorczyk, Olga Szemraj, Janusz Bieniasz, Magdalena Cebula, Barbara Giannopoulos, Krzysztof Balcerczak, Ewa Jesionek-Kupnicka, Dorota Kowal, Malgorzata Kostyra, Aleksandra Calbecka, Malgorzata Wawrzyniak, Ewa Mirowski, Marek Kordek, Radzislaw Robak, Tadeusz 1055-9965 1538-7755 American Association for Cancer Research (AACR) Oncology Epidemiology http://dx.doi.org/10.1158/1055-9965.epi-08-0683 <jats:title>Abstract</jats:title><jats:p>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&gt;G) and missense rs1800561 (418C&gt;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 &lt; 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)</jats:p> <i>CD38</i>Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians Cancer Epidemiology, Biomarkers & Prevention |
| spellingShingle | Jamroziak, Krzysztof, Szemraj, Zofia, Grzybowska-Izydorczyk, Olga, Szemraj, Janusz, Bieniasz, Magdalena, Cebula, Barbara, Giannopoulos, Krzysztof, Balcerczak, Ewa, Jesionek-Kupnicka, Dorota, Kowal, Malgorzata, Kostyra, Aleksandra, Calbecka, Malgorzata, Wawrzyniak, Ewa, Mirowski, Marek, Kordek, Radzislaw, Robak, Tadeusz, Cancer Epidemiology, Biomarkers & Prevention, CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians, Oncology, Epidemiology |
| title | CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_full | CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_fullStr | CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_full_unstemmed | CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_short | CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| title_sort | <i>cd38</i>gene polymorphisms contribute to genetic susceptibility to b-cell chronic lymphocytic leukemia: evidence from two case-control studies in polish caucasians |
| title_unstemmed | CD38Gene Polymorphisms Contribute to Genetic Susceptibility to B-Cell Chronic Lymphocytic Leukemia: Evidence from Two Case-Control Studies in Polish Caucasians |
| topic | Oncology, Epidemiology |
| url | http://dx.doi.org/10.1158/1055-9965.epi-08-0683 |