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- Attarbaschi, A., et al.
(author)
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Second malignant neoplasms after treatment of non-Hodgkin’s lymphoma—a retrospective multinational study of 189 children and adolescents
- 2021
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 35, s. 534-549
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Journal article (peer-reviewed)abstract
- Data on the spectrum of second malignant neoplasms (SMNs) after primary childhood non-Hodgkin’s lymphoma (NHL) are scarce. One-hundred-and-eighty-nine NHL patients diagnosed in a 30 years period of 1980–2010 developing an SMN were retrieved from 19 members of the European Intergroup for Childhood NHL and/or the international Berlin-Frankfurt-Münster Study Group. Five subgroups of SMNs were identified: (1) myeloid neoplasms (n = 43; 23%), (2) lymphoid neoplasms (n = 51; 27%), (3) carcinomas (n = 48; 25%), (4) central nervous system (CNS) tumors (n = 19; 10%), and (5) “other” SMNs (n = 28; 15%). In 37 patients (20%) preexisting disorders were reported with 90% having any kind of cancer predisposition syndrome (CPS). For the 189 primary NHL patients, 5-year overall survival (OS) after diagnosis of an SMN was 56 ± 4%, being worst for patients with preexisting disorders at 28 ± 8%. Five-year OS rates were 38 ± 8%, 59 ± 7%, 79 ± 8%, 34 ± 12%, and 62 ± 11%, respectively, for patients with myeloid and lymphoid neoplasms, carcinomas, CNS tumors, and “other” SMNs (p < 0.0001). Patients with SMNs after childhood NHL having a reported CPS, mostly mismatch repair disorders, carried a very poor prognosis. Moreover, although outcome was favorable in some subtypes of SMNs after childhood NHL (carcinomas, lymphoid neoplasms), other SMNs such as myeloid neoplasms and CNS tumors had a dismal prognosis. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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- Gregory, J. M., et al.
(author)
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How accurately can the climate sensitivity to CO2 be estimated from historical climate change?
- 2020
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In: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 54:1-2, s. 129-157
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Journal article (peer-reviewed)abstract
- The equilibrium climate sensitivity (ECS, in K) to CO2 doubling is a large source of uncertainty in projections of future anthropogenic climate change. Estimates of ECS made from non-equilibrium states or in response to radiative forcings other than 2×CO2 are called “effective climate sensitivity” (EffCS, in K). Taking a “perfect-model” approach, using coupled atmosphere–ocean general circulation model (AOGCM) experiments, we evaluate the accuracy with which CO2 EffCS can be estimated from climate change in the “historical” period (since about 1860). We find that (1) for statistical reasons, unforced variability makes the estimate of historical EffCS both uncertain and biased; it is overestimated by about 10% if the energy balance is applied to the entire historical period, 20% for 30-year periods, and larger factors for interannual variability, (2) systematic uncertainty in historical radiative forcing translates into an uncertainty of±30 to 45% (standard deviation) in historical EffCS, (3) the response to the changing relative importance of the forcing agents, principally CO2 and volcanic aerosol, causes historical EffCS to vary over multidecadal timescales by a factor of two. In recent decades it reached its maximum in the AOGCM historical experiment (similar to the multimodel-mean CO2 EffCS of 3.6 K from idealised experiments), but its minimum in the real world (1.6 K for an observational estimate for 1985–2011, similar to the multimodel-mean value for volcanic forcing). The real-world variations mean that historical EffCS underestimates CO2 EffCS by 30% when considering the entire historical period. The difference for recent decades implies that either unforced variability or the response to volcanic forcing causes a much stronger regional pattern of sea surface temperature change in the real world than in AOGCMs. We speculate that this could be explained by a deficiency in simulated coupled atmosphere–ocean feedbacks which reinforce the pattern (resembling the Interdecadal Pacific Oscillation in some respects) that causes the low EffCS. We conclude that energy-balance estimates of CO2 EffCS are most accurate from periods unaffected by volcanic forcing. Atmosphere GCMs provided with observed sea surface temperature for the 1920s to the 1950s, which was such a period, give a range of about 2.0–4.5 K, agreeing with idealised CO2 AOGCM experiments; the consistency is a reason for confidence in this range as an estimate of CO2 EffCS. Unless another explosive volcanic eruption occurs, the first 30 years of the present century may give a more accurate energy-balance historical estimate of this quantity.
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- Merlo, Domenico Franco, et al.
(author)
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Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression : The NewGeneris Cohort
- 2014
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:2, s. 193-200
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Journal article (peer-reviewed)abstract
- Background: Leukemia incidence has increased in recent decades among European children, -suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M(1)dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M(1)dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX (R) (chemically activated luciferase expression for androgens) (8 genes), ER alpha CALUX (R) (for estrogens) (2 genes), and DR CALUX (R) (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/ 2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research.
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