1. |
- Mattsson, Niklas, et al.
(author)
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Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
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In: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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2. |
- Mattsson, Niklas, et al.
(author)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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3. |
- Bright, Chloe J, et al.
(author)
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Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe
- 2018
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 110:6
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Journal article (peer-reviewed)abstract
- Background: Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer.Methods: We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated.Results: Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma.Conclusions: For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.
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4. |
- Byrne, Julianne, et al.
(author)
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The PanCareSurFup consortium : research and guidelines to improve lives for survivors of childhood cancer
- 2018
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In: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 103:Nov, s. 238-248
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Journal article (peer-reviewed)abstract
- Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case-control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.
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5. |
- Fidler, Miranda M., et al.
(author)
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Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe
- 2018
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 110:2
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Journal article (peer-reviewed)abstract
- Introduction: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors.Methods: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided.Results: Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk.Conclusions: For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer.
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6. |
- Grabow, Desiree, et al.
(author)
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The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer : a cohort from 12 European countries
- 2018
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 33:3, s. 335-349
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Journal article (peer-reviewed)abstract
- Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.
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