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Association of Genetic Variants in ARID5B, IKZF1 and CEBPE with Risk of Childhood de novo B-Lineage Acute Lymphoblastic Leukemia in India

  • Bhandari, Prerana (Research and Development, SRL Ltd.) ;
  • Ahmad, Firoz (Research and Development, SRL Ltd.) ;
  • Mandava, Swarna (Cytogenetic Division, SRL Ltd.) ;
  • Das, Bibhu Ranjan (Research and Development, SRL Ltd.)
  • Published : 2016.08.01

Abstract

Background: Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous genetic disease and its etiology remains poorly understood. Recent genome wide association and replication studies have highlighted specific polymorphisms contributing to childhood ALL predispositions mostly in European populations. It is unclear if these observations generalize to other populations with a lower incidence of ALL. The current case-control study evaluated variants in ARID5B (rs7089424, rs10821936), IKZF1 (rs4132601) and CEBPE (rs2239633) genes, which appear most significantly associated with risk of developing childhood B-lineage ALL. Materials and Methods: Using TaqMan assays, genotyping was conducted for 162 de novo B-lineage ALL cases and 150 unrelated healthy controls in India. Appropriate statistical methods were applied. Results: Genotypic and allelic frequencies differed significantly between cases and controls at IKZF1-rs4132601 (p=0.039, p=0.015) and ARID5B-rs10821936 (p=0.028, p=0.026). Both rs10821936 (p=0.019; OR 0.67; 95% CI=0.47-0.94) and rs4132601 (p=0.018; OR 0.67; 95%CI 0.48-0.94) were associated with reduced disease risk. Moreover, gender-analysis revealed male-specific risk associations for rs10821936 (p=0.041 CT+CC) and rs4132601 (p=0.005 G allele). Further, ARID5B-rs7089424 and CEBPE-rs2239633 showed a trend towards decreased disease risk but without significance (p=0.073; p=0.73). Conclusions: Our findings provide the first evidence that SNPs ARID5B-rs10821936 and IKZF1-rs4132601 are associated with decreased B-lineage ALL susceptibility in Indian children. Understanding the effects of these variants in different ethnic groups is crucial as they may confer different risk of ALL within different populations.

Keywords

Childhood ALL;ARID5B;IKZF1;CEBPE;genetic susceptibility

References

  1. Bhandari P, Ahmad F, Dalvi R, et al (2015). Cytogenetic Profile of De Novo B lineage Acute Lymphoblastic Leukemia: Determination of Frequency, Distribution Pattern and Identification of Rare and Novel Chromosomal Aberrations in Indian Patients. Asian Pac J Cancer Prev, 16, 7219-29. https://doi.org/10.7314/APJCP.2015.16.16.7219
  2. Chokkalingam AP, Hsu L-I, Metayer C, et al (2013). Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics. Cancer Causes Control, 24, 1789-95. https://doi.org/10.1007/s10552-013-0256-3
  3. Dai Y, Tang L, Healy J, Sinnett D (2014). Contribution of Polymorphisms in IKZF1 Gene to Childhood Acute Leukemia: A Meta-Analysis of 33 Case-Control Studies. PLoS ONE, 9, 113748. https://doi.org/10.1371/journal.pone.0113748
  4. Ellinghaus E, Stanulla M, Richter G, et al (2012). Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic. Leukemia, 26, 902-9. https://doi.org/10.1038/leu.2011.302
  5. Fletcher O, Houlston RS (2010). Architecture of inherited susceptibility to common cancer. Nat Rev Cancer, 10, 353-61. https://doi.org/10.1038/nrc2840
  6. Georgopoulos K, Bigby M, Wang J-H, et al (1994). The ikaros gene is required for the development of all lymphoid lineages. Cell, 79, 143-56. https://doi.org/10.1016/0092-8674(94)90407-3
  7. Gutierrez-Camino A, Lopez-Lopez E, Martin-Guerrero I, et al (2013). Intron 3 of the ARID5B gene: a hot spot for acute lymphoblastic leukemia susceptibility. J Cancer Res Clin Oncol, 139, 1879-86. https://doi.org/10.1007/s00432-013-1512-3
  8. Han S, Lee K-M, Park SK, et al (2010). Genome-wide association study of childhood acute lymphoblastic leukemia in Korea. Leuk Res, 34, 1271-4. https://doi.org/10.1016/j.leukres.2010.02.001
  9. Healy J, Richer C, Bourgey M, Kritikou EA, Sinnett D (2010). Replication analysis confirms the association of ARID5B with childhood B-cell acute lymphoblastic leukemia. Haematologica, 95, 1608-11. https://doi.org/10.3324/haematol.2010.022459
  10. Jiang Y, Hou J, Zhang Q, et al (2013). The MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: an updated meta-analysis based on 37 case-control studies. Asian Pac J Cancer Prev, 14, 6357-62. https://doi.org/10.7314/APJCP.2013.14.11.6357
  11. Kennedy AE, Kamdar KY, Lupo PJ, et al (2015). Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk. Leuk Lymphoma, 56, 169-74. https://doi.org/10.3109/10428194.2014.910662
  12. Kreile M, Rots D, Piekuse L, et al (2014). Lack of association between polymorphisms in genes MTHFR and MDR1 with risk of childhood acute lymphoblastic leukemia. Asian Pac J Cancer Prev, 15, 9707-11. https://doi.org/10.7314/APJCP.2014.15.22.9707
  13. Lautner-Csorba O, Gezsi A, Semsei AF, et al (2012). Candidate gene association study in pediatric acute lymphoblastic leukemia evaluated by Bayesian network based Bayesian multilevel analysis of relevance. BMC Med Genomics, 5, 1-15. https://doi.org/10.1186/1755-8794-5-1
  14. Li S, Ren L, Fan L, Wang G (2014). IKZF1 rs4132601 polymorphism and acute lymphoblastic leukemia susceptibility: a meta-analysis. Leuk Lymphoma, 56, 1-13.
  15. Lin C, Song W, Bi X, et al (2014a). Recent advances in the ARID family: focusing on roles in human cancer. OncoTargets Ther, 7, 315-24.
  16. Lin C-Y, Li M-J, Chang J-G, et al (2014b). High-resolution melting analyses for genetic variants in ARID5B and IKZF1 with childhood acute lymphoblastic leukemia susceptibility loci in Taiwan. Blood Cells Mol Dis, 52, 140-5. https://doi.org/10.1016/j.bcmd.2013.10.003
  17. Mullighan CG, Su X, Zhang J, et al (2009). Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med, 360, 470-80. https://doi.org/10.1056/NEJMoa0808253
  18. Orsi L, Rudant J, Bonaventure A, et al (2012). Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE). Leukemia, 26, 2561-4. https://doi.org/10.1038/leu.2012.148
  19. Pan Y, Chen H, Liang H, Wang X, Wang L (2014). Meta-analysis of the association between CCAAT/enhancer binding protein-$\varepsilon$ polymorphism and the risk of childhood acute lymphoblastic leukemia. Int J Clin Exp Med, 7, 5553-7.
  20. Papaemmanuil E, Hosking FJ, Vijayakrishnan J, et al (2009). Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet, 41, 1006-10. https://doi.org/10.1038/ng.430
  21. Pastorczak A, Gorniak P, Sherborne A, et al (2011). Role of 657del5 NBN mutation and 7p12.2 (IKZF1), 9p21 (CDKN2A), 10q21.2 (ARID5B) and 14q11.2 (CEBPE) variation and risk of childhood ALL in the Polish population. Leuk Res, 35, 1534-6. https://doi.org/10.1016/j.leukres.2011.07.034
  22. Pongstaporn W, Pakakasama S, Chaksangchaichote P, et al (2015). MDR1 C3435T and C1236T polymorphisms: association with high-risk childhood acute lymphoblastic leukemia. Asian Pac J Cancer Prev, 16, 2839-43. https://doi.org/10.7314/APJCP.2015.16.7.2839
  23. Prasad RB, Hosking FJ, Vijayakrishnan J, et al (2010). Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood. Blood, 115, 1765-7. https://doi.org/10.1182/blood-2009-09-241513
  24. Sole X, Guino E, Valls J, Iniesta R, Moreno V (2006). SNPStats: a web tool for the analysis of association studies. Bioinformatics, 22, 1928-9. https://doi.org/10.1093/bioinformatics/btl268
  25. Trevino LR, Yang W, French D, et al (2009). Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet, 41, 1001-5. https://doi.org/10.1038/ng.432
  26. Vijayakrishnan J, Sherborne AL, Sawangpanich R, et al (2010). Variation at 7p12.2 and 10q21.2 influences childhood acute lymphoblastic leukemia risk in the Thai population and may contribute to racial differences in leukemia incidence. Leuk Lymphoma, 51, 1870-4. https://doi.org/10.3109/10428194.2010.511356
  27. Walsh KM, Chokkalingam AP, Hsu L-I, et al (2013). Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children. Leukemia, 27, 2416-9. https://doi.org/10.1038/leu.2013.130
  28. Wang Y, Chen J, Li J, et al (2013). Association of three polymorphisms in ARID5B, IKZF1and CEBPE with the risk of childhood acute lymphoblastic leukemia in a Chinese population. Gene, 524, 203-7. https://doi.org/10.1016/j.gene.2013.04.028
  29. Xu H, Cheng C, Devidas M, et al (2012). ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia. J Clin Oncol, 30, 751-7. https://doi.org/10.1200/JCO.2011.38.0345
  30. Yadav SP, Rastogi N, Kharya G, et al (2014). Barriers to Cure for children with cancer in india and strategies to improve outcomes: a report by the indian pediatric hematology oncology group. Pediatr Hematol Oncol, 31, 217-24. https://doi.org/10.3109/08880018.2014.893596
  31. Yang W, Trevino LR, Yang JJ, et al (2010). ARID5B SNP rs10821936 is associated with risk of childhood acute lymphoblastic leukemia in blacks and contributes to racial differences in leukemia incidence. Leukemia, 24, 894-6. https://doi.org/10.1038/leu.2009.277
  32. Zeng H, Wang XB, Cui NH, et al (2014). Associations between AT-rich Interactive Domain 5B gene Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia: a Metaanalysis. Asian Pac J Cancer Prev, 15, 6211-7. https://doi.org/10.7314/APJCP.2014.15.15.6211