title: Amerindian genetic ancestry and INDEL polymorphisms associated with susceptibility of childhood B-cell Leukemia in an admixed population from the Brazilian Amazon.
abstract: Acute lymphoblastic leukemia (ALL) is a malignant tumor common in children. Studies of genetic susceptibility to cancer using biallelic insertion/deletion (INDEL) type polymorphisms associated with cancer development pathways may help to clarify etymology of ALL. In this study, we investigate the role of eight functional INDEL polymorphisms and influence of genetic ancestry to B-cell ALL susceptibility in children of Brazilian Amazon population, which has a high degree of inter-ethnic admixture. Ancestry analysis was estimated using a panel of 48 autosomal ancestry informative markers. 130 B-cell ALL patients and 125 healthy controls were included in this study. The odds ratios and 95% confidence intervals were adjusted for confounders. The results indicated an association between the investigated INDEL polymorphisms in CASP8 (rs3834129), CYP19A1 (rs11575899) e XRCC1 (rs3213239) genes in the development of B-cell ALL. The carriers of Insertion/Insertion (Ins/Ins) genotype of the polymorphism in CASP8 gene presented reduced chances of developing B-cell ALL (P=0.001; OR=0.353; 95% CI=0.192-0.651). The Deletion/Deletion (Del/Del) genotype of the polymorphism in CYP19A1 gene was associated to a lower chance of developing B-cell ALL (P=3.35×10-6; OR=0.121; 95% CI=0.050-0.295), while Del/Del genotype of the polymorphism in XRCC1 gene was associated to a higher chance of developing B-cell ALL (P=2.01×10-4; OR=6.559; 95% CI=2.433-17.681). We also found that Amerindian ancestry correlates with the risk of B-cell ALL. For each increase of 10% in the Amerindian ancestry results in 1.4-fold chances of developing B-cell ALL (OR=1.406; 95% IC=1.123-1.761), while each increase of 10% in the European ancestry presents a protection effect in the development of B-cell ALL (OR=0.666; 95% IC=0.536-0.827). The results suggest that genetic factors influence leukemogenesis and might be explored in the stratification of B-cell ALL risk in admixed populations.
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: darlen.c.carvalho@gmail.com.
authors: Darlen C
authors: DC
authors: Carvalho
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Hospital Ophir Loyola, Departamento de Pediatria, Belém, Pará, PA, Brazil. Electronic address: alaydevieira@yahoo.com.br.
authors: Alayde V
authors: AV
authors: Wanderley
authors: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: marcosmata52@yahoo.com.br.
authors: Marcos A T
authors: MA
authors: Amador
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: fernandesmr@yahoo.com.br.
authors: Marianne R
authors: MR
authors: Fernandes
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: giovannaccavalcante@gmail.com.
authors: Giovanna C
authors: GC
authors: Cavalcante
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: karlacereja.ufpa@gmail.com.
authors: Karla B C C
authors: KB
authors: Pantoja
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil. Electronic address: fernando.mellojr@hotmail.com.
authors: Fernando A R
authors: FA
authors: Mello
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil. Electronic address: assumpcaopp@gmail.com.
authors: Paulo P
authors: PP
authors: de Assumpção
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil. Electronic address: khayatas@gmail.com.
authors: André S
authors: AS
authors: Khayat
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: akely@ufpa.br.
authors: Ândrea
authors: Â
authors: Ribeiro-Dos-Santos
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: sidneysantos@ufpa.br.
authors: Sidney
authors: S
authors: Santos
authors: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, PA, Brazil; Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Belém, Pará, PA, Brazil. Electronic address: npcsantos@yahoo.com.br.
authors: Ney P C
authors: NP
authors: Dos Santos
keywords: Amerindian genetic ancestry; B-cell acute lymphoblastic leukemia (B-cell ALL); CASP8; CYP19A1; Cancer susceptibility; XRCC1