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IDENTIFYING CHILDHOOD LEUKEMIA WITH AN EXCESS OF HEMATOLOGICAL MALIGNANCIES IN FIRST-DEGREE RELATIVES IN BRAZIL
Childhood Leukemia
Familial History of Hematological Disorders
Lymphoblastic Acute Leukemia
Myeloid Leukemia
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Department of Hematology. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Câncer. Research Center. Rio de Janeiro, RJ, Brasil / University of Minnesota. Department of Pediatrics. Division of Epidemiology and Clinical Research. Minneapolis, MN, USA.
Instituto Nacional de Câncer. Research Center. Rio de Janeiro, RJ, Brasil.
Hospital Foundation of Hematology and Hemotherapy of Amazonas. Department of Pediatric Hematology. Manaus, AM, Brazil.
Children's Hospital of Brasília Jose Alencar. Department of Pediatric Hematology. Brasília, DF, Brazil.
Children's Oncological and Hematological Treatment Center - Rosa Pedrossian Regional Hospital. Department of Pediatric Hematology. Campo Grande, MS, Brazil.
National Cancer Institute. Research Center. Rio de Janeiro, RJ, Brazil.
University of Minnesota. Department of Pediatrics. Division of Epidemiology and Clinical Research. Minneapolis, MN, USA.
National Cancer Institute. Research Center. Rio de Janeiro, RJ, Brazil.
Instituto Nacional de Câncer. Research Center. Rio de Janeiro, RJ, Brasil.
Hospital Foundation of Hematology and Hemotherapy of Amazonas. Department of Pediatric Hematology. Manaus, AM, Brazil.
Children's Hospital of Brasília Jose Alencar. Department of Pediatric Hematology. Brasília, DF, Brazil.
Children's Oncological and Hematological Treatment Center - Rosa Pedrossian Regional Hospital. Department of Pediatric Hematology. Campo Grande, MS, Brazil.
National Cancer Institute. Research Center. Rio de Janeiro, RJ, Brazil.
University of Minnesota. Department of Pediatrics. Division of Epidemiology and Clinical Research. Minneapolis, MN, USA.
National Cancer Institute. Research Center. Rio de Janeiro, RJ, Brazil.
Abstract
Background: Familial aggregation in childhood leukemia is associated with epidemiological and genomic factors. Albeit epidemiological studies on the familial history of hematological malignancies (FHHMs) are scarce, genome-wide studies have identified inherited gene variants associated with leukemia risk. We revisited a dataset of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients to explore the familial aggregation of malignancies among their relatives. Methods: A series of 5,878 childhood leukemia (≤21 years of age) from the EMiLI study (2000-2019) were assessed. Lack of well-documented familial history of cancer (FHC) and 670 cases associated with genetic phenotypic syndromes were excluded. Leukemia subtypes were established according to World Health Organization recommendations. Logistic regression-derived odds ratios (ORs) and 95% confidence intervals (CIs) were performed and adjusted by age as a continuous variable, where ALL was the reference group for AML and conversely. The pedigree of 18 families with excess hematological malignancy was constructed. Results: FHC was identified in 472 of 3,618 eligible cases (13%). Ninety-six of the 472 patients (20.3%) had an occurrence of FHHMs among relatives. Overall, FHC was significantly associated with AML (OR, 1.36; 95% CI, 1.01-1.82; p = 0.040). Regarding the first-degree relatives, the OR, 2.92 95% CI,1.57-5.42 and the adjOR, 1.16 (1.03-1.30; p0.001) were found for FHC and FHHM, respectively. Conclusion: Our findings confirmed that AML subtypes presented a significant association with hematological malignancies in first-degree relatives. Genomic studies are needed to identify germline mutations that significantly increase the risk of developing myeloid malignancies in Brazil.
Keywords
BrazilChildhood Leukemia
Familial History of Hematological Disorders
Lymphoblastic Acute Leukemia
Myeloid Leukemia
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