Association of genetic variation inIKZF1, ARID5B, CDKN2A, andCEBPEwith the risk of acute lymphoblastic leukemia in Tunisian children and their contribution to racial differences in leukemia incidence

Abstract

Recent genome-wide association studies (GWAS) focusing on pediatric acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15 years old, have found evidence that single-nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2), CDKN2A (9p21.3), and CEBPE (14q11.2) are strongly associated to the risk of developing pediatric ALL. These studies have been conducted in European and Thai populations, and it is unclear whether these observations generalize to other populations with a lower incidence of pediatric ALL. In order to explore the impact of these variants on pediatric ALL risk in the Tunisian population, we genotyped 58 cases of pediatric ALL and 150 controls for SNPs rs4132601 (7p12.2), rs7089424 (10q21.2), rs3731217 (9p21.3), and rs2239633 (14q11.2). Our results, which are consistent with findings in European populations, show that 3 SNPs, i.e., rs4132601 (P = .00116, odds ratio [OR] = 2.78, 95% confidence interval [CI] = [1.42, 5.87]), rs7089424 (P = .0022, OR = 0.49, 95% CI = [0.31, 0.79]), and rs2239633 (P = .0010, OR = 0.47, 95% CI = [0.29, 0.75]) are significantly associated with a higher risk of developing pediatric ALL (P < .05). Furthermore, we show differences in allele frequencies in SNPs between Tunisian and Caucasian and/or Thai populations (e.g., CEBPE, rs2239633; population attributable risk [PAR] ∼15-fold the PAR of Thai population). These differences, combined with differences in linkage disequilibrium structure between populations and differences in size between populations, may contribute to racial differences in pediatric ALL incidence.

An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana‐Farber Cancer Institute ALL Consortium protocol 05‐001

“…Additionally, we did not analyze incidence of poor prognostic indicators, including BCR-ABL1-like subtype and deletions of the Ikaros (IKZF1) gene, both of which have been reported to be more common in Hispanic patients. [36][37][38]41 These two features, which are frequently observed together, are independently associated with adverse outcomes in children with ALL. Thus, the inferior EFS and OS that we observed in Hispanic patients may be due to overrepresentation of these unfavorable biologic features within this population.…”

“…11,33 For example, we observed a significantly lower incidence of the favorable ETV6-RUNX1 (TEL/AML1) fusion, in our Hispanic cohort, which may have contributed to a higher risk of relapse. 34 We 15,16 and others 20,[35][36][37][38][39][40] have previously described associations between functional genetic polymorphisms and TRT or survival among children with leukemia and the prevalence of some of these polymorphisms is known to differ between ethnic groups. 11,20,33,[41][42][43] In exploratory analyses, we targeted a small subset of polymorphisms that were relatively common (population prevalence of at least 10%) and that could potentially impact either TRT or survival.…”

Association of SNPs in CDKN2A (P14ARF) Tumour Suppressor Gene With Endometrial Cancer in Postmenopausal Women

“…The rs3731217 polymorphism has been previously associated with ALL in the Caucasians, and the minor G allele within the SNP was found to be protective against paediatric BCP-ALL (18,31). In turn, the incidence rates of the T allele have been found to be similar, both among cases and controls for paediatric ALL in the Tunisian population (32). Among patients with HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP), the carriers of the TT genotype have been reported to have an increased risk either for death or for the recurrence of the disease, as compared to TG or GG genotypes (17).…”

Impact ofMDM2, TP53andP14ARFPolymorphisms on Endometrial Cancer Risk and Onset

“…The polymorphism rs3731217 of P14ARF has been reported to be correlated with ALL in Caucasians, and the G allele to be protective against paediatric B-cell precursor ALL in vivo 33: 917-924 (2019) 920 (19,20). In turn, among Tunisian children with ALL, the T allele in rs3731217, has been found to be distributed similarly among cancerous and non-cancerous patients (21). The GG-GA genotypes of rs3731245 have been shown to be associated with an increased risk of small vessel subtype of ischemic stroke, while the GA-AA genotypes -with reduced risk of chronic benzene poisoning (22,23).…”