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.
Original language | English (US) |
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Article number | 1207695 |
Journal | Frontiers in Oncology |
Volume | 13 |
DOIs | |
State | Published - 2023 |
Bibliographical note
Funding Information:This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq #481104/2012-7) Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, E-26/110.712/2012) and TUCCA-Associação para Crianças e Adolescentes com Cancer, São Paulo, Brazil. MSPO is supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq [#310877/2019-9]), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ CNE #E-26/102.337/2013; CNE #E-26/202.577-2019), the Children’s Cancer Research Fund, and the University of Minnesota, Twin Cities. Acknowledgments
Publisher Copyright:
Copyright © 2023 Mendes-de-Almeida, Andrade, Sampaio Carvalho, Córdoba, Souza, Neto, Spector and Pombo-de-Oliveira.
Keywords
- Brazil
- childhood leukemia
- familial history of hematological disorders
- lymphoblastic acute leukemia
- myeloid leukemia
PubMed: MeSH publication types
- Journal Article