Focused screening of a panel of cancer‐related genetic polymorphisms reveals new susceptibility loci for pediatric acute lymphoblastic leukemia

Offenmüller, Sonja; Ravindranath, Y.; Goyette, Gerard; Kanakapalli, Deepa; Miller, Kathryn S.; Brecht, Ines B.; Zolk, Oliver

doi:10.1002/pbc.25011

Cited by 2 publications

(2 citation statements)

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“…The heritable basis of susceptibility to ALL is further supported by recent candidate gene and genome-wide association studies (GWAS), suggesting that co-inheritance of multiple germline variants may contribute to the risk of the disease. Five GWAS have been performed with populations of 3 275 ALL cases and 4 817 healthy control individuals [ 8 ]. Four independent loci have been shown conclusively to be associated with ALL, and more specifically the B-cell precursor (BCP) ALL risk was associated with the particular SNPs located in 7p12.2 ( IKZF1 ), 9p12 ( CDKN2A/CDKN2B ), 10q21.2 ( ARID5B ) and 14q11.2 ( CEBPE ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population

Kreile¹,

Piekuse²,

Rots³

et al. 2016

aoms

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IntroductionChildhood acute lymphoblastic leukaemia (ALL) is a complex disease caused by a combination of genetic susceptibility and environmental exposure. Previous genome-wide association studies have reported several single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. Several variations in genes encoding enzymes involved in carcinogenesis are suggested as being associated with an increased risk of ALL development.Material and methodsWe enrolled 77 paediatric ALL patients and 122 healthy controls, and in addition parental DNA was also available for 45 probands. SNPs rs10821936 (ARID5B), rs4132601 (IKZF1), rs2239633 (CEBPE), rs3731217 (CDKN2A) and rs1800566 (NQO1) and the presence of GSTT1 and GSTM1 null variants were detected. For statistical analysis the hybrid method of two designs ‘Haplin’ was used as well as linkage disequilibrium for family-based association studies.ResultsWe identified the SNP rs10821936 in the ARID5B gene as being statistically significantly associated with childhood ALL, especially if the C allele is in a homozygous state, relative risk (RR) 4.65, 95% CI: 2.03–10.6, p = 0.0006. Statistically significant differences were not found in other SNPs. We found risk combinations including all five variations, the strongest association being found in a combination where all five genetic variants are in a homozygous state, CCTTTTTTCC, p = 0.032.ConclusionsThe identified SNP rs10821936 could serve as a potential risk marker for childhood ALL development. Further studies in an independent population are needed for verification.

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Section: Introductionmentioning

confidence: 99%

Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population

Kreile¹,

Piekuse²,

Rots³

et al. 2016

aoms

View full text Add to dashboard Cite

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“…The heritable susceptibility to ALL is proven by the finding of recent candidate-gene and genome-wide association studies (GWAS). Some authors suggested that ALL risk is associated with multiple germline variants [12]; others disprove these hypotheses suggesting that the genetic susceptibility to ALL is mediated by a small number of genes with a strong effect rather than the cumulative effect of small genes [13]. In fact, the first GWAS performed by Trevino and colleagues, identified eighteen germline single nucleotide polymorphisms (SNPs) of 307,944 subjects with allele frequencies are higher in pediatric ALL population that in non-ALL controls ( p < 1 × 10–5) [9].…”

Section: Introductionmentioning

confidence: 99%

IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study

et al. 2019

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Background Associations between IKZF1 gene variants and Acute Lymphoblastic Leukemia (ALL) was recently reported. We examined whether the common IKZF1 polymorphisms rs4132601 T/G and rs111978267 A/G are associated with ALL among a Tunisian pediatric cohort. Methods This case-control study involved 170 patients with ALL and 150 control subjects. SNP genotyping was performed by TaqMan® SNP Genotyping Assay. Results The minor allele G of IKZF1 gene polymorphism rs4132601 T/G was significantly higher in ALL cases than in control subjects (P = 0.029), with 1.54-fold increased risk of ALL. The association of rs4132601 with ALL was seen under co-dominant (P = 0.009), recessive (P = 0.006), and additive (P = 0.027) genetic models, of which the co-dominant (P = 0.027) and recessive (P = 0.027) association remained significant after adjusting for covariates, and False Discovery Rate correction. In contrast, no association was noted for rs111978267 variant. Two-locus (rs4132601-rs11978267) IKZF1 haplotype analysis demonstrated association of GA (P = 0.053), with increased ALL risk [OR (95% CI) = 1.58 (1.00–2.51)], which remained significant after controlling for key covariates [aP = 0.046; aOR (95% CI) = 1.61 (1.01–2.57)]. Conclusion We demonstrated the association of IKZF1 polymorphism rs4132601 T/G with increased risk of ALL among Tunisian pediatric cohort, with altered phenotypic changes among ALL patients.

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Focused screening of a panel of cancer‐related genetic polymorphisms reveals new susceptibility loci for pediatric acute lymphoblastic leukemia

Abstract: These findings reveal two independent novel susceptibility loci for childhood ALL.

Cited by 2 publications

References 46 publications

Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population

Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population

IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study

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