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- Panagopoulou, Paraskevi, et al.
(författare)
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Parental age and the risk of childhood acute myeloid leukemia : results from the Childhood Leukemia International Consortium
- 2019
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 59, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- Background:Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent.Aim:To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies.Material/methods: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants < 1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period.Results:Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers >= 40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year.Conclusions:An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.
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| 2. |
- Thomopoulos, Thomas P, et al.
(författare)
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Prelabor cesarean delivery and early-onset acute childhood leukemia risk.
- 2016
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Ingår i: European Journal of Cancer Prevention. - 0959-8278 .- 1473-5709. ; 25:2, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (≤3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996-2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0-14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10-2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13-2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15-2.40 and ORprelaborCD=1.79, 95% CI: 1.21-2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor.
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| 3. |
- Kourti, Maria, et al.
(författare)
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CK1 delta restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1 alpha/ARNT complex formation
- 2015
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Ingår i: Cellular Signalling. - : Elsevier BV. - 0898-6568 .- 1873-3913. ; 27:6, s. 1129-1140
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation of cells under hypoxia is facilitated by metabolic adaptation, mediated by the transcriptional activator Hypoxia Inducible Factor-1 (HIF-1). HIF-1 alpha, the inducible subunit of HIF-1 is regulated by oxygen as well as by oxygen-independent mechanisms involving phosphorylation. We have previously shown that CK1 delta phosphorylates HIP-la in its N-terminus and reduces its affinity for its heterodimerization partner ARNT. To investigate the importance of this mechanism for cell proliferation under hypoxia, we visually monitored HIP-1 alpha interactions within the cell nucleus using the in situ proximity ligation assay (PIA) and fluorescence recovery after photobleaching (FRAP). Both methods show that CK1 delta-dependent modification of HIF-1 alpha impairs the formation of a chromatin binding HIF-1 complex. This is confirmed by analyzing expression of lipin-1, a direct target of HIF-1 that mediates hypoxic neutral lipid accumulation. Inhibition of CK1 delta increases lipid droplet formation and proliferation of both cancer and normal cells specifically under hypoxia and in an HIF-1 alpha- and lipin-1-dependent manner. These data reveal a novel role for CK1 delta in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions.
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