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- Title
Association between the TPMT*3C (rs1142345) Polymorphism and the Risk of Death in the Treatment of Acute Lymphoblastic Leukemia in Children from the Brazilian Amazon Region.
- Authors
Cardoso de Carvalho, Darlen; Pereira Colares Leitão, Luciana; Mello Junior, Fernando Augusto Rodrigues; Vieira Wanderley, Alayde; Souza, Tatiane Piedade de; Borges Andrade de Sá, Roberta; Cohen-Paes, Amanda; Rodrigues Fernandes, Marianne; Santos, Sidney; Salim Khayat, André; Pimentel de Assumpção, Paulo; Pereira Carneiro dos Santos, Ney
- Abstract
Acute lymphoblastic leukemia (ALL) is the leading cause of death from pediatric cancer worldwide. However, marked ethnic disparities are found in the treatment of childhood ALL with less effective results and higher mortality rates being obtained in populations with a high level of Native American ancestry. Genetic variations of the patient can affect resistance to ALL chemotherapy and potentially play an important role in this disparity. In the present study, we investigated the association of 16 genetic polymorphisms with the cell and metabolic pathways of the chemotherapeutic agents used in the treatment of ALL with the risk of death in treating childhood ALL in patients with a high contribution of Amerindian ancestry, coming from the Brazilian Amazon. The study included 121 patients with B-cell ALL treated with the BFM-2002 protocol. We are the first to identify the association between the TPMT gene rs1142345 polymorphism and the high risk of death in treating childhood ALL. Patients with the CC genotype had an approximately 25.5 times higher risk of dying during treatment of the disease than patients with other genotypes (p = 0.019). These results may help elucidate how the patient's genetic characteristics contribute to the mortality disparity in populations with a high contribution of Native American ancestry. The rs1142345 variant of the TPMT gene could be used as a potential marker to early stratify patients at high risk of death in treating childhood ALL in the investigated population.
- Subjects
LYMPHOBLASTIC leukemia; ACUTE leukemia; CHILD mortality; CHILDHOOD cancer; GENETIC polymorphisms; NATIVE Americans
- Publication
Genes, 2020, Vol 11, Issue 10, p1132
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes11101132