Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia
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Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia. / Søegaard, Signe Holst; Rostgaard, Klaus; Skogstrand, Kristin; Wiemels, Joseph Leo; Schmiegelow, Kjeld; Hjalgrim, Henrik.
I: Cancer Research, Bind 78, Nr. 18, 15.09.2018, s. 5458-5463.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia
AU - Søegaard, Signe Holst
AU - Rostgaard, Klaus
AU - Skogstrand, Kristin
AU - Wiemels, Joseph Leo
AU - Schmiegelow, Kjeld
AU - Hjalgrim, Henrik
N1 - ©2018 American Association for Cancer Research.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - It has been proposed that children with acute lymphoblastic leukemia (ALL) are born with a dysregulated immune function that together with postnatal environmental exposures causes childhood ALL. Despite its importance for the understanding of ALL etiology, this hypothesis has been inadequately explored. In a population-based case-control study, we measured the concentrations of 10 cytokines and other inflammatory markers on neonatal dried blood spots from 178 children who at ages 1 to 9 years were diagnosed with B-cell precursor ALL and 178 matched controls. Through linkage with Danish nationwide registers, we also assessed whether neonatal inflammatory markers were associated with previously demonstrated risk factors for childhood ALL. Children who developed B-cell precursor ALL had significantly lower neonatal concentrations of IL8, soluble IL6 receptor (sIL6R) α, TGFβ1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP) and higher concentrations of IL6, IL17, and IL18 compared with matched controls. Concentrations of IL10 were below the detection level for both patients and controls. Birth order (IL18 and CRP), gestational age (sIL6Rα, TGFβ1, and CRP), and sex (sIL6Rα, IL8, and CRP), but not maternal age, infections during pregnancy, birth weight nor mode of delivery were significantly associated with the neonatal concentrations of inflammatory markers. Our findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function.Significance: Children who develop acute lymphoblastic leukemia are immunologically distinct at birth and could potentially react abnormally to infections in early childhood. Cancer Res; 78(18); 5458-63. ©2018 AACR.
AB - It has been proposed that children with acute lymphoblastic leukemia (ALL) are born with a dysregulated immune function that together with postnatal environmental exposures causes childhood ALL. Despite its importance for the understanding of ALL etiology, this hypothesis has been inadequately explored. In a population-based case-control study, we measured the concentrations of 10 cytokines and other inflammatory markers on neonatal dried blood spots from 178 children who at ages 1 to 9 years were diagnosed with B-cell precursor ALL and 178 matched controls. Through linkage with Danish nationwide registers, we also assessed whether neonatal inflammatory markers were associated with previously demonstrated risk factors for childhood ALL. Children who developed B-cell precursor ALL had significantly lower neonatal concentrations of IL8, soluble IL6 receptor (sIL6R) α, TGFβ1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP) and higher concentrations of IL6, IL17, and IL18 compared with matched controls. Concentrations of IL10 were below the detection level for both patients and controls. Birth order (IL18 and CRP), gestational age (sIL6Rα, TGFβ1, and CRP), and sex (sIL6Rα, IL8, and CRP), but not maternal age, infections during pregnancy, birth weight nor mode of delivery were significantly associated with the neonatal concentrations of inflammatory markers. Our findings support the hypothesis that children who later develop B-cell precursor ALL are born with a dysregulated immune function.Significance: Children who develop acute lymphoblastic leukemia are immunologically distinct at birth and could potentially react abnormally to infections in early childhood. Cancer Res; 78(18); 5458-63. ©2018 AACR.
U2 - 10.1158/0008-5472.CAN-18-0831
DO - 10.1158/0008-5472.CAN-18-0831
M3 - Journal article
C2 - 30217873
VL - 78
SP - 5458
EP - 5463
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 18
ER -
ID: 220860858