61 results on '"Kenborg L"'
Search Results
2. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
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Meijer, A, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Falck-Winther, J, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LC, Kruseova, J, Pluijm, SMF, Kuehni, CF, van der Pal, H, Parfitt, R, Spix, C, Hesping, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD, Bhavsar, AP, am Zehnhoff-Dinnesen, A, Carleton, BC, Zolk, O, van den Heuvel-Eibrink, M, Meijer, A, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garrè, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Falck-Winther, J, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LC, Kruseova, J, Pluijm, SMF, Kuehni, CF, van der Pal, H, Parfitt, R, Spix, C, Hesping, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drögemöller, BI, Ross, CJD, Bhavsar, AP, am Zehnhoff-Dinnesen, A, Carleton, BC, Zolk, O, and van den Heuvel-Eibrink, M
- Abstract
Background: Ototoxicity (hearing loss, tinnitus and/or vertigo) is a serious adverse event of cisplatin treatment in children with cancer. The heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. This study investigated the association between carriership of novel single nucleotide polymorphisms (SNPs) and cisplatin-induced hearing loss (CIHL) in childhood cancer patients.Material and methods: The discovery cohort included cisplatin treated, non-cranial irradiated pediatric cancer patients within the European PanCareLIFE (PCL) study (N=390). CIHL at end of cancer treatment was defined as Muenster grade >=2b, assessed by pure tone audiometry. DNA was genotyped using the Infinium© Global Screening Array. Logistic regression models were applied including age at diagnosis, sex, cisplatin total cumulative dose and principal components 1-4, assuming an additive effect of the minor allele. Replication of the findings was performed in two independent, similarly treated cohorts (N=192 and N=188). Functional validation experiments in cultured human HeLa cell lines were performed to determine the effect of knockdown of the SNPs nearest identified gene on cisplatin-induced toxicity.Results: In the PCL discovery cohort, 8 SNPs reached a suggestive significance of P<1.0x10-5. One variant (rs893507) within the TCERG1L gene showed evidence of replication (P=0.01) in the Canadian first replication cohort. Analysis in the PCL second replication cohort confirmed this finding (P=1.0x10-4). The combined analysis showed that carriership of the C-allele of this newly discovered variant increases the odds of CIHL with 3.11-fold (P=5.3x10-10, 95% CI 2.2-4.5). Modulating TCERG1L expression significantly altered cell viability in response to cisplatin treatment, where TCERG1L overexpression and silencing protected and sensitized cells to cisplatin toxicity, respectively.Discussion: Children with cancer who carry a variant in the TCERG1L g
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- 2021
3. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
- Author
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Meijer, A. J.M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C.H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J.E., van der Kooi, A. L.F., Kremer, L. C.M., Kruseova, J., Pluijm, S. M.F., Kuehni, C. E., van der Pal, H. J.H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J.C.M.M., Rassekh, S. R., Wright, G. E.B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., Ross, C. J.D., Meijer, A. J.M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C.H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., Winther, J. F., Rechnitzer, C., Hasle, H., Kepak, T., Kepakova, K., Tissing, W. J.E., van der Kooi, A. L.F., Kremer, L. C.M., Kruseova, J., Pluijm, S. M.F., Kuehni, C. E., van der Pal, H. J.H., Parfitt, R., Spix, C., Tillmanns, A., Deuster, D., Matulat, P., Calaminus, G., Hoetink, A. E., Elsner, S., Gebauer, J., Haupt, R., Lackner, H., Blattmann, C., Neggers, S. J.C.M.M., Rassekh, S. R., Wright, G. E.B., Brooks, B., Nagtegaal, A. P., Drögemöller, B. I., and Ross, C. J.D.
- Abstract
In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.
- Published
- 2021
4. Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset
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Langer, T. (Thomas), Clemens, E. (Eva), Broer, L. (Linda), Maier, L. (Lara), Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Grotel, M. (Martine) van, Pluijm, S.F.M. (Saskia F.M.), Binder, H. (Harald), Mayer, B. (Benjamin), von dem Knesebeck, A. (Annika), Byrne, J. (Julianne), Dulmen-den Broeder, E. (Eline) van, Crocco, M. (Marco), Grabow, D. (Desiree), Kaatsch, P. (Peter), Kaiser, M. (Melanie), Spix, C. (Claudia), Kenborg, L. (Line), Winther, J.F. (Jeanette F.), Rechnitzer, C. (Catherine), Hasle, H. (Henrik), Kepak, T. (Tomas), Kooi, A.L.F. (Anne-Lotte) van der, Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Bielack, S. (Stefan), Sorg, B. (Benjamin), Hecker-Nolting, S. (Stefanie), Kuehni, C. (Claudia), Ansari, M. (Marc), Kompis, M. (Martin), van der Pal, H.J. (Heleen J.), Parfitt, R. (Ross), Deuster, D. (Dirk), Matulat, P. (Peter), Tillmanns, A. (Amelie), Tissing, W.J.E. (Wim), Beck, J.D. (Jörn D.), Elsner, S. (Susanne), am Zehnhoff-Dinnesen, A. (Antoinette), Heuvel-Eibrink, M.M. (Marry) van den, Zolk, O. (Oliver), Langer, T. (Thomas), Clemens, E. (Eva), Broer, L. (Linda), Maier, L. (Lara), Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Grotel, M. (Martine) van, Pluijm, S.F.M. (Saskia F.M.), Binder, H. (Harald), Mayer, B. (Benjamin), von dem Knesebeck, A. (Annika), Byrne, J. (Julianne), Dulmen-den Broeder, E. (Eline) van, Crocco, M. (Marco), Grabow, D. (Desiree), Kaatsch, P. (Peter), Kaiser, M. (Melanie), Spix, C. (Claudia), Kenborg, L. (Line), Winther, J.F. (Jeanette F.), Rechnitzer, C. (Catherine), Hasle, H. (Henrik), Kepak, T. (Tomas), Kooi, A.L.F. (Anne-Lotte) van der, Kremer, L.C.M. (Leontien), Kruseova, J. (Jarmila), Bielack, S. (Stefan), Sorg, B. (Benjamin), Hecker-Nolting, S. (Stefanie), Kuehni, C. (Claudia), Ansari, M. (Marc), Kompis, M. (Martin), van der Pal, H.J. (Heleen J.), Parfitt, R. (Ross), Deuster, D. (Dirk), Matulat, P. (Peter), Tillmanns, A. (Amelie), Tissing, W.J.E. (Wim), Beck, J.D. (Jörn D.), Elsner, S. (Susanne), am Zehnhoff-Dinnesen, A. (Antoinette), Heuvel-Eibrink, M.M. (Marry) van den, and Zolk, O. (Oliver)
- Abstract
Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment.
- Published
- 2020
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5. Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset
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Langer, T, Clemens, Eva, Broer, Linda, Maier, L, Uitterlinden, André, Vries, ACH, van Grotel, Martine, Pluijm, Saskia F.M., Binder, H, Mayer, Benjamin, von dem Knesebeck, A, Byrne, J, van Dulmen-den Broeder, E, Crocco, M, Grabow, D, Kaatsch, P, Kaiser, M, Spix, C, Kenborg, L, Winther, JF, Rechnitzer, C, Hasle, H, Kepak, T, Kooi, Anne-Lotte, Kremer, LC, Kruseova, J, Bielack, S, Sorg, B, Hecker-Nolting, S, Kuehni, CE, Ansari, M, Kompis, M, van der Pal, HJ, Parfitt, R, Deuster, D, Matulat, P, Tillmanns, A, Tissing, WJ, Beck, JD, Elsner, S, am Zehnhoff-Dinnesen, A, Eibrink, Marry, Zolk, O, Langer, T, Clemens, Eva, Broer, Linda, Maier, L, Uitterlinden, André, Vries, ACH, van Grotel, Martine, Pluijm, Saskia F.M., Binder, H, Mayer, Benjamin, von dem Knesebeck, A, Byrne, J, van Dulmen-den Broeder, E, Crocco, M, Grabow, D, Kaatsch, P, Kaiser, M, Spix, C, Kenborg, L, Winther, JF, Rechnitzer, C, Hasle, H, Kepak, T, Kooi, Anne-Lotte, Kremer, LC, Kruseova, J, Bielack, S, Sorg, B, Hecker-Nolting, S, Kuehni, CE, Ansari, M, Kompis, M, van der Pal, HJ, Parfitt, R, Deuster, D, Matulat, P, Tillmanns, A, Tissing, WJ, Beck, JD, Elsner, S, am Zehnhoff-Dinnesen, A, Eibrink, Marry, and Zolk, O
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- 2020
6. Confirmation of genetic risk markers of platinum-induced ototoxicity
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Tillmanns, A, Parfitt, R, Matulat, P, Abdel-Kahaar, E, Maier, L, Zolk, O, Elsner, S, Wolschon, EM, Kuehni, CE, Kuonen, R, Weiss, A, Garré, ML, Kepak, T, Kepakova, K, Kruseova, J, Luks, A, Falck Winther, J, Kenborg, L, Lackner, H, Bielack, S, van den Heuvel-Eibrink, M, Calaminus, G, Baust, K, Beck, J, Kremer, L, Clemens, E, Langer, T, am Zehnhoff-Dinnesen, A, and PanCareLIFE consortium
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ddc: 610 - Abstract
Background: Platinum compounds such as cisplatin or carboplatin are potent antineoplastic agents widely used for a variety of cancer types. Unfortunately, their use leads to dose-limiting side effects such as ototoxicity. Our study aimed at investigating the predictive value of 11 candidate genetic markers in a large non-selected pediatric population of cancer survivors who had been treated with cisplatin and/or carboplatin.Materials and Methods: As a part of the PanCareLIFE study, the ototoxicity study included 2,696 survivors from 7 European countries treated with cisplatin and/or carboplatin for childhood cancer, resulting in the largest clinical European cohort assembled for this late-effect study. Hearing loss was audiologically classified using the Münster Classification. Three groups were defined, i.e., no hearing loss, minor hearing loss, and clinically relevant hearing loss. Patients were genotyped for single nucleotide polymorphisms (SNPs) in 7 candidate genes. Genetic association analyses were performed considering non-genetic covariates.Results: 900 patients were included in the final genetic analysis. Multinomial logistic regression was performed to model the relationship between the predictors and membership in the hearing loss group. The model explained 25% of the variance in hearing loss and correctly classified 58% of cases. Significant unique contributions were made by SLC22A2 rs316019 (P=0.017), age at the start of platinum treatment (P=1.46x10-17), cranial radiation (P=5.42x10-6), and the cumulative dose of cisplatin (P=5.86x10-19). Addition of the rs316019 genetic marker to the non-genetic risk factors (age, dose, cranial radiation) improved the area under the ROC curve only marginally (0.731 vs. 0.730).Discussion: Our study confirmed one potential genetic marker, rs316019 in SLC22A2. Its predictive value, however, is low.Conclusion: Due to the heterogeneity of results from genetic association studies performed so far, the evidence seems not yet sufficient to recommend screening for specific markers. Advances in the understanding of the pathophysiologic mechanisms of cisplatin-induced ototoxicity, as well as future genome-wide association studies, may help identify suitable genetic markers.Acknowledgement: This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030.
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- 2019
7. Platin treatment and hearing loss: initial audiological results from PanCareLIFE
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Parfitt, R, Tillmanns, A, Matulat, P, Deuster, D, Elsner, S, Wolschon, EM, Kuehni, CE, Kuonen, R, Weiss, A, Garré, ML, Kepak, T, Kepakova, K, Kruseova, J, Luks, A, Falck Winther, J, Kenborg, L, Lackner, H, Bielack, S, van den Heuvel-Eibrink, M, Calaminus, G, Baust, K, Beck, J, Kremer, L, Clemens, E, Langer, T, Zolk, O, and am Zehnhoff-Dinnesen, A
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ddc: 610 - Abstract
Background: Cisplatin and carboplatin are widely used in paediatric cancer treatment. Cisplatin especially can have long-term side effects, including sensorineural hearing loss. The aim of this study is to define the risk factors for platin-related ototoxicity.Materials and Methods: As part of the PanCareLIFE consortium, we gathered audiological data from 13 pan-European clinics. Eligible patients were 20 dB HL at any frequency).A total of 2,696 patients with 10,320 audiograms from various stages of cancer treatment were obtained. Audiometric data were quality-checked and classified (Münster and SIOP classifications) and 736 patients with sufficient data were phenotyped. A logistic regression investigated the likelihood of developing a hearing loss >=Münster 2b (thresholds >40 dB HL at >=4 kHz) after treatment given age, gender, cisplatin dose and cranial irradiation.Results: 48.2% of 1,385 patients with a post-treatment audiogram had clinically-relevant hearing loss (defined as >=Münster 2b) after platin treatment.Children 15 years (odds ratio 2.7, 95% CI 1.5-4.9, p=0.0006). Patients with a cumulative cisplatin dose >450 mg/m2 were more likely to develop hearing loss than those treated with carboplatin alone (OR 12.5, 95% CI 6.8-23.0, p=3.7x10-16). Treatment with cranial irradiation was more likely to lead to hearing loss than without (OR 4.5, 95% CI 3.0-6.7, p=7.2x10-13).Discussion: This is the first study of platin ototoxicity with such a large sample size. The results support tendencies found in previous studies with smaller groups. The high risk groups identified here must be monitored regularly for ototoxicity. Further detailed analyses into audiological changes and possible pharmacogenetic confounders are planned.Conclusion: 48% of patients treated with cisplatin develop clinically-relevant hearing loss. Age
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- 2019
8. Genetic determinants of ototoxicity during and after childhood cancer treatment: Protocol for the pancarelife study
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Clemens, E. (Eva), Meijer, A.J.M. (Annelot J.M.), Broer, L. (Linda), Langer, T. (Thomas), Kooi, A.L.F. (Anne-Lotte) van der, Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Kuehni, C. (Claudia), Garrè, M.L. (Maria L.), Kepak, T. (Tomas), Kruseova, J. (Jarmila), Winther, J.F. (Jeanette F.), Kremer, L.C.M. (Leontien), Dulmen-den Broeder, E. (Eline) van, Tissing, W.J.E. (Wim), Rechnitzer, C. (Catherine), Kenborg, L. (Line), Hasle, H. (Henrik), Grabow, D. (Desiree), Parfitt, R. (Ross), Binder, H. (Harald), Carleton, B.C. (Bruce), Byrne, J. (Julianne), Kaatsch, P. (Peter), Zehnhoff-Dinnesen, A. (Antoinetteam), Zolk, O. (Oliver), Heuvel-Eibrink, M.M. (Marry) van den, Clemens, E. (Eva), Meijer, A.J.M. (Annelot J.M.), Broer, L. (Linda), Langer, T. (Thomas), Kooi, A.L.F. (Anne-Lotte) van der, Uitterlinden, A.G. (André), Vries, A.C.H. (Andrica) de, Kuehni, C. (Claudia), Garrè, M.L. (Maria L.), Kepak, T. (Tomas), Kruseova, J. (Jarmila), Winther, J.F. (Jeanette F.), Kremer, L.C.M. (Leontien), Dulmen-den Broeder, E. (Eline) van, Tissing, W.J.E. (Wim), Rechnitzer, C. (Catherine), Kenborg, L. (Line), Hasle, H. (Henrik), Grabow, D. (Desiree), Parfitt, R. (Ross), Binder, H. (Harald), Carleton, B.C. (Bruce), Byrne, J. (Julianne), Kaatsch, P. (Peter), Zehnhoff-Dinnesen, A. (Antoinetteam), Zolk, O. (Oliver), and Heuvel-Eibrink, M.M. (Marry) van den
- Abstract
Background: Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common adverse effect in children treated with cisplatin-based chemotherapy or cranial radiotherapy. Ototoxicity can extend from high-tone hearing impairment to involvement of speech frequencies. Hearing impairment can impede speech and language and neurocognitive development. Although treatment-related risk factors for hearing loss following childhood cancer treatment have been identified, the individual variability in toxicity of adverse effects after similar treatment between childhood cancer patients suggests a role for genetic susceptibility. Currently, 12 candidate gene approach studies have been performed to identify polymorphisms predisposing to platinum-induced ototoxicity in children being treated for cancer. However, results were inconsistent and most studies were underpowered and/or lacked replication. Objective: We describe the design of the PanCareLIFE consortium's work packages that address the genetic susceptibility of platinum-induced ototoxicity. Methods: As a part of the PanCareLIFE study within the framework of the PanCare consortium, we addressed genetic susceptibility of treatment-induced ototoxicity during and after childhood cancer treatment in a large European cohort by a candidate gene approach and a genome-wide association screening. Results: This study included 1124 survivors treated with cisplatin, carboplatin, or cranial radiotherapy for childhood cancer, resulting in the largest clinical European cohort assembled for this late effect to date. Within this large cohort we defined a group of 598 cisplatin-treated childhood cancer patients not confounded by cranial radiotherapy. The PanCareLIFE initiative provided, for the first time, a unique opportunity to confirm already identi
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- 2019
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9. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study
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Clemens, Eva, Meijer, AJM, Broer, Linda, Langer, T, van der Kooi, Anne-Lotte, Uitterlinden, André, de Vries, A.C.H., Kuehni, CE, Garre, ML, Kepak, T, Kruseova, J, Winther, JF, Kremer, LC, van Dulmen-den Broeder, E, Tissing, WJ, Rechnitzer, C, Kenborg, L, Hasle, H, Grabow, D, Parfitt, R, Binder, H, Carleton, BC, Byrne, J, Kaatsch, P, Zehnhoff-Dinnesen, AA, Zolk, O, Van den Heuvel - Eibrink, Marry, Clemens, Eva, Meijer, AJM, Broer, Linda, Langer, T, van der Kooi, Anne-Lotte, Uitterlinden, André, de Vries, A.C.H., Kuehni, CE, Garre, ML, Kepak, T, Kruseova, J, Winther, JF, Kremer, LC, van Dulmen-den Broeder, E, Tissing, WJ, Rechnitzer, C, Kenborg, L, Hasle, H, Grabow, D, Parfitt, R, Binder, H, Carleton, BC, Byrne, J, Kaatsch, P, Zehnhoff-Dinnesen, AA, Zolk, O, and Van den Heuvel - Eibrink, Marry
- Published
- 2019
10. TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.
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Meijer, A. J. M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C. H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garrè, M. L., Grabow, D., Kaatsch, P., Kaiser, M., Kenborg, L., and Winther, J. F.
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DEAFNESS ,CHILDHOOD cancer ,CISPLATIN ,HUMAN cell culture ,PATHOLOGICAL physiology - Abstract
In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10
−10 , OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
11. Outdoor work and risk for Parkinson's disease: a population-based case-control study
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Kenborg, L., primary, Lassen, C. F., additional, Ritz, B., additional, Schernhammer, E. S., additional, Hansen, J., additional, Gatto, N. M., additional, and Olsen, J. H., additional
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- 2010
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12. Early mortality in children with cancer in Denmark and Sweden: The role of social background in a setting with universal healthcare.
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Mogensen H, Erdmann F, Mader L, Vrelits Sørensen G, Talbäck M, Tjørnelund Nielsen T, Hasle H, Heyman M, Winther JF, Feychting M, Tettamanti G, and Kenborg L
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- Child, Humans, Cohort Studies, Sweden, Denmark, Universal Health Care, Neoplasms
- Abstract
Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (OR
adj_Low_vs_High 1.65 [95% CI 1.22-2.23]) and income (ORadj_Q1(lowest)_vs_Q4(highest) 1.77 [1.25-2.49]). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)- Published
- 2024
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13. The impact of the temporal sequence of cranial radiotherapy and platin-based chemotherapy on hearing impairment in pediatric and adolescent CNS and head-and-neck cancer patients: A report from the PanCareLIFE consortium.
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Scobioala S, Parfitt R, Matulat P, Byrne J, Langer T, Troschel FM, Hesping AE, Clemens E, Kaatsch P, Grabow D, Kaiser M, Spix C, Kremer LC, Calaminus G, Baust K, Kuehni CE, Weiss A, Strebel S, Kuonen R, Elsner S, Haupt R, Garré ML, Gruhn B, Kepak T, Kepakova K, Winther JF, Kenborg L, Rechnitzer C, Hasle H, Kruseova J, Luks A, Lackner H, Bielack S, Beck JD, Jürgens H, van den Heuvel-Eibrink MM, Zolk O, Eich HT, and Am Zehnhoff-Dinnesen A
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- Humans, Child, Adolescent, Central Nervous System, Cranial Irradiation, Hearing Loss chemically induced, Hearing Loss epidemiology, Hearing Loss, Sensorineural chemically induced, Hearing Loss, Sensorineural epidemiology, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy
- Abstract
The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium. Audiological outcomes were compared between patients who received CRT prior to PCth and those who received it afterwards. The incidence, degree and posttreatment progression of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated in 141 patients. One hundred and nineteen patients were included in a time-to-onset analysis. Eighty-eight patients received CRT prior to PCth (Group 1) and 53 patients received PCth before CRT (Group 2). Over a median follow-up time of 1.6 years, 72.7% of patients in Group 1 experienced SNHL ≥ MS2b compared to 33.9% in Group 2 (P < .01). A time-to-onset analysis was performed for 74 patients from Group 1 and 45 patients from Group 2. Median time to hearing loss (HL) ≥ MS2b was 1.2 years in Group 1 and 4.4 years in Group 2 (P < .01). Thus, audiological outcomes were better for patients who received CRT after PCth than before. This finding should be further evaluated and considered within clinical practice in order to minimize hearing loss in children and adolescents with CNS and HN tumors., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2024
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14. Pregnancy outcomes in female survivors of neuroblastoma: a short report from the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study.
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Azizi A, Norsker FN, Kokla M, Nielsen TT, Holmqvist AS, Øra I, Vettenranta K, Øfstaas H, Hasle H, Rechnitzer C, Winther JF, and Kenborg L
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- Child, Adult, Humans, Female, Pregnancy, Pregnancy Outcome epidemiology, Scandinavian and Nordic Countries epidemiology, Survivors, Neoplasms, Neuroblastoma epidemiology
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- 2023
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15. Employment, occupation, and income in adults with neurofibromatosis 1 in Denmark: a population- and register-based cohort study.
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Kenborg L, Frederiksen LE, Galanakis M, Doser K, Nielsen TT, Doherty MA, Hove H, Østergaard JR, Handrup MM, Ejerskov C, Mulvihill JJ, and Winther JF
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- Humans, Adult, Middle Aged, Cohort Studies, Employment, Occupations, Denmark epidemiology, Registries, Neurofibromatosis 1
- Abstract
Background: Little is known about employment status, occupation, and disposable income in adults with NF1., Methods: From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980-2019., Results: Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61-0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16-3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82-0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years., Conclusion: Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families., (© 2023. The Author(s).)
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- 2023
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16. Endocrine morbidity in neurofibromatosis 1: a nationwide, register-based cohort study.
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Kenborg L, Ebbehoj A, Ejerskov C, Handrup MM, Østergaard JR, Hove H, Doser K, Krøyer A, Mulvihill JJ, Winther JF, and Stochholm K
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- Humans, Female, Cohort Studies, Morbidity, Neurofibromatosis 1 epidemiology, Diabetes Mellitus, Type 2 complications, Adrenal Gland Neoplasms complications, Endocrine System Diseases epidemiology, Endocrine System Diseases complications
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Objective: Previous studies have found that neurofibromatosis 1 (NF1) is associated with an increased risk for endocrine disorders, but no comprehensive overview of the risk for specific endocrine disorders has been published. We assessed endocrine morbidity in individuals with NF1 from information on hospital admissions, surgery for endocrine disorders, and relevant medication., Design: A nationwide population registry-based cohort study., Methods: We identified 2467 individuals with NF1 diagnosed between 1977 and 2013 from the Danish National Patient Register and the RAREDIS database and 20 132 randomly sampled age- and sex-matched population comparisons. Information on endocrine diseases was identified using registrations of discharge diagnoses, surgery, and medication prescriptions. The rates of endocrine disorders in individuals with NF1 were compared with those in the comparison cohort in Cox proportional hazard models., Results: Individuals with NF1 had a higher rate than the comparison group of any endocrine discharge diagnosis (hazard ratio [HR] 1.72, 95% confidence interval [CI]: 1.58-1.87), endocrine-related surgery (2.03, 1.39-2.96), and prescribed medications (1.32, 1.23-1.42). Increased HRs were observed for diseases and surgical operations of several glands, including pheochromocytoma, and for osteoporosis, and osteoporotic fractures. Decreased rates were observed with drugs for type 2 diabetes. Women with NF1 had higher HRs for surgery of the ovaries, uterus, and sterilization, but lower rates of surgeries of cervix and prescriptions for birth control pills., Conclusions: Neurofibromatosis 1 is associated with a variety of endocrine disorders, surgery, and medication related to endocrine disease. Awareness of endocrine morbidity is important in the clinical follow-up of individuals with NF1., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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17. Childhood cancer confers increased risk of migraine - A Danish nationwide register study.
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Davidsson OB, Rostgaard K, Hjalgrim LL, Chalmer MA, Olofsson IA, Søegaard SH, Winther JF, Kenborg L, Hansen TF, and Hjalgrim H
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Background: Investigations of migraine among childhood cancer survivors have predominantly relied on self-reported information and hospital discharge diagnoses. Alone, both approaches are liable to bias. We used Danish nationwide registers to obtain data on both prescriptions of acute migraine medications (antimigraines) and hospital discharge diagnoses of migraine to assess the relative risk of migraine across a wider spectrum of migraine presentations than previously studied., Methods: We followed a Danish population-based cohort of 7771 individuals with childhood cancer diagnosed in the period from Jan 1st, 1978 to Dec 31st, 2017, for risk of prescription antimigraine initiation and for risk of hospitalization due to migraine. Rates of hospitalization were assessed for the entire follow-up period whereas rates of antimigraine initiations were assessed in the period from Jan 1st, 1997, to Dec 31st, 2017. Relative to the general population without childhood cancer, standardized incidence ratios (SIRs) were calculated for each outcome., Results: Individuals exposed to childhood cancer were at increased risk of antimigraine initiation (SIR of 1.24, 95% CI: 1.11-1.38) and of migraine hospitalization (SIR of 2.44, 95% CI: 1.87-3.12) from the day of their cancer diagnosis and up to 40 years after., Conclusions: Individuals diagnosed with childhood cancer have a higher risk of migraine of varying presentations, in addition to migraine resulting in hospitalization as previously reported. This potentially preventable problem warrants clinical attention., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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18. School performance of children with neurofibromatosis 1: a nationwide population-based study.
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Doser K, Belmonte F, Andersen KK, Østergaard JR, Hove H, Handrup MM, Ejerskov C, Mulvihill JJ, Winther JF, and Kenborg L
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- Child, Female, Humans, Adolescent, Schools, Students psychology, Parents, Neurofibromatosis 1 epidemiology, Neurofibromatosis 1 psychology, Academic Performance
- Abstract
Children with neurofibromatosis 1 (NF1) may have a high burden of somatic disease and cognitive impairments, which can lead to poor academic performance. We evaluated school grades from exams ending mandatory schooling (usually around age 15 or 16 years) of children with NF1 in a population-based registry study using a within-school matched design. The study included 285 children with NF1 and 12,000 NF1-free peers who graduated from the same school and year during 2002-2015. We estimated overall and gender-specific grades by subject and compared the grades of children with NF1 with those of NF1-free peers in linear regression models. We also examined the effect of social and socioeconomic factors (immigration status and parental education, income and civil status) on grades and age at finalizing ninth grade. School grades varied considerably by socioeconomic stratum for all children; however, children with NF1 had lower grades by an average of 11-12% points in all subjects. In the adjusted models, children with NF1 had significantly lower grades than their NF1-free peers, with largest negative differences in grades observed for girls with NF1. Finally, children with NF1 were 0.2 (CI 0.1-0.2) years older than their peers on graduating from ninth grade, but only maternal educational modified the age at graduating. In conclusion, students with NF1 perform more poorly than their peers in all major school subjects. Gender had a strong effect on the association between NF1 and school grades; however, socioeconomic factors had a similar effect on grades for children with NF1 and their peers., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)
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- 2022
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19. Neurocognitive function and health-related quality of life in a nationwide cohort of long-term childhood brain tumor survivors.
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Helligsoe ASL, Henriksen LT, Kenborg L, Lassen-Ramshad Y, Wu LM, Winther JF, Hasle H, and Amidi A
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Background: Childhood brain tumor survivors are at high risk of late effects, especially neurocognitive impairment. Limited data are available examining neurocognitive function and associations with quality of life (QoL) in childhood brain tumor survivors. Our aim was to examine neurocognitive function in childhood brain tumor survivors, and associations with QoL and symptom burden., Methods: Five-year survivors of brain tumors over the age of 15 were identified in the Danish Childhood Cancer Registry ( n = 423). Eligible and consenting participants completed neuropsychological tests and questionnaires assessing QoL, insomnia, fatigue, anxiety, and depression. Survivors treated with radiation ( n = 59) were statistically compared with survivors not treated with radiation ( n = 102)., Results: In total, 170 survivors participated (40.2% participation rate). Sixty-six percent of the survivors who completed neurocognitive tests ( n = 161) exhibited overall neurocognitive impairment. Survivors treated with radiation, especially whole-brain irradiation, exhibited poorer neurocognitive outcomes than survivors not treated with radiation. Neurocognitive outcomes for survivors treated with surgery were below normative expectations. Furthermore, a number of survivors experienced significant fatigue (40%), anxiety (23%), insomnia (13%), and/or depression (6%). Survivors treated with radiation reported lower quality of life (QoL) and higher symptom burden scores than survivors not treated with radiation; particularly in physical functioning, and social functioning with symptoms of fatigue. Neurocognitive impairment was not associated with QoL or symptom burden., Conclusions: In this study, a majority of the childhood brain tumor survivors experienced neurocognitive impairment, reduced QoL, and high symptom burden. Although not associated with each other, it is apparent that childhood brain tumor survivors experience not only neurocognitive dysfunction but may also experience QoL impairments and significant symptom burden., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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20. Cohort profile: life with neurofibromatosis 1 - the Danish NF1 cohort.
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Doser K, Hove H, Østergaard JR, Bidstrup PE, Dalton SO, Handrup MM, Ejerskov C, Krøyer A, Doherty MA, Møllegaard Jepsen JR, Mulvihill JJ, Winther JF, and Kenborg L
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- Adult, Cohort Studies, Denmark epidemiology, Female, Humans, Pregnancy, Quality of Life, Registries, Neurofibromatosis 1 epidemiology
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Purpose: The Danish neurofibromatosis 1 (NF1) cohort was initiated to study health-related, socioeconomic and psychological consequences of living with the monogenetic disorder NF1 using a nationwide and population-based approach., Participants: The cohort includes all 2467 individuals in Denmark who were hospitalised with or due to NF1 from 1977 to 2013 or registered in the RAREDIS Database (1995-2013), a national clinical database for rare diseases, or both. A comparison cohort matched to individuals with NF1 on sex and date of birth was identified in the Civil Registration System (n=20 132)., Findings to Date: All cohort members were linked to the unique Danish registries to obtain information on hospital contacts, birth outcomes, education and partnership. A questionnaire was completed by 244 of the 629 adult cohort members with NF1 registered in the RAREDIS Database to evaluate the psychosocial and emotional burden. Further, neuropsychological tests were performed on 103 adult cohort members with NF1 and 38 adult population comparisons. To date, six studies have been published. Individuals with NF1 had an increased risk for (1) hospitalisation for disorders affecting all organ systems of the body throughout all decades of life, (2) psychiatric disorders, (3) attaining a short or medium long education and (4) not forming a life partner. Women with NF1 had an increased risk for spontaneous abortions and stillbirths. Finally, adults with NF1 had an impaired quality of life and a high need for professional support for physical, psychological and work-related problems, which was partly associated with disease severity and visibility., Future Plans: The cohort will regularly be updated with newly diagnosed patients in the RAREDIS Database as well as with outcome information in the Danish registries. New studies are in progress to assess other medical and socioeconomic dimensions of living with NF1., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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21. Effects of early maternal cancer and fertility treatment on the risk of adverse birth outcomes.
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Everhøj C, Norsker FN, Rechnitzer C, Licht SF, Nielsen TT, Kjær SK, Jensen A, Hargreave M, Christensen J, Belmonte F, Urhoj SK, Strandberg-Larsen K, Winther JF, and Kenborg L
- Abstract
Background: Early maternal cancer and fertility treatment each increase the risk for adverse birth outcomes, but the joint effect of these outcomes has not yet been reported. Thus, the aim was to assess the individual and joint effect of maternal cancer and fertility treatment on the risk for adverse birth outcomes., Methods: This population-based cohort study included 5487 live-born singletons identified in the Danish Medical Birth Register (1994-2016) of mothers with previous cancer (<40 years) recorded in the Danish Cancer Registry (1955-2014). We randomly selected 80,262 live-born singletons of mothers with no cancer <40 years matched to mothers with cancer by birth year and month. We calculated odds ratios (ORs) for preterm birth, low birth weight (LBW) (<2500 g) and small for gestational age (SGA), mean differences in birth weight in grams, and additional cases of preterm birth (gestational age<259 days) per 100,000 person-years. Multiplicative and additive interaction of maternal cancer and fertility treatment was compared with outcomes of children conceived naturally to mothers with no maternal cancer (reference group)., Findings: Among 84,332 live-born singletons, increased ORs for preterm birth were observed among children born to mothers with previous cancer (1·48, 95% confidence interval [CI] 1·33-1.65) or after fertility treatment (1·43, 95% 1·28-1-61), with 22 additional cases of preterm birth among both group of children (95% CI 15-29; 95% CI 14-30). In the joint analyses, the OR for SGA for children born after fertility treatment to mothers with previous cancer was similar to that of the reference group (OR 1·02, 95% CI 0·72-1·44, P for interaction=0·52). Children with both exposures had increased ORs for LBW (1·86, 95% CI 1·17-2·96, P for interaction=0·06) and preterm birth (2·31, 955 CI 1·66-3·20, P for interaction = 0·56), with 61 additional cases of preterm birth (95% CI 27-95, P for interaction=0.26) over that of children in the reference group. The mean birth weight was also lower in children born to mothers with both exposures (-140 g, 95% CI -215; -65) ( P for interaction=0.06) but decreased to -22 g (95% CI -76; 31) after adjustment for GA., Interpretation: Although we did not find any statistically significant additive interaction between maternal cancer and fertility treatment, children born after fertility treatment of mothers with previous cancer were at increased risk for adverse birth outcomes. Thus, pregnant women with both exposures need close follow-up during pregnancy., Funding: The Danish Cancer Society and the Danish Childhood Cancer Foundation., Competing Interests: After finalizing her master thesis and this study, Cathrine Everhøj started as a full time employee at Danske Regioner, which is a public employer organization of the five regions in Denmark responsible for the healthcare system. Filippa Nyboe Norsker and Sofie de Fine Licht have finalized their postdoctoral work and started as full time employees at the Danish Medicines Council and AstraZeneca, respectively. None of the other authors has any conflicts of interest., (© 2022 The Author(s).)
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- 2022
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22. Pregnancy outcomes in women with neurofibromatosis 1: a Danish population-based cohort study.
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Kenborg L, Boschini C, Bidstrup PE, Dalton SO, Doser K, Nielsen TT, Krøyer A, Johansen C, Frederiksen K, Sørensen SA, Hove H, Østergaard JR, Mulvihill JJ, and Winther JF
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- Cohort Studies, Denmark epidemiology, Female, Humans, Middle Aged, Pregnancy, Pregnancy Outcome, Registries, Stillbirth epidemiology, Abortion, Spontaneous epidemiology, Neurofibromatosis 1 complications, Neurofibromatosis 1 epidemiology, Neurofibromatosis 1 genetics
- Abstract
Background: The probability of a pregnancy, live birth, stillbirth and abortion has never been assessed in women with neurofibromatosis 1 (NF1) in a large population-based study., Methods: We included 1006 women (15-49 years) registered with NF1 in the Danish National Patient Registry or followed in two national Centers for Rare Diseases and 10 020 women from the Danish population. Information on pregnancy outcomes was ascertained from health registries. Cumulative incidence, mean cumulative count, hazard ratios (HRs) and proportion ratios (PRs) with 95% CIs were calculated., Results: The cumulative incidence of a first pregnancy at age 50 years was slightly lower in women with NF1 (74%; 95% CI 70 to 77) than in population comparisons (78%; 95% CI 77 to 79). When all pregnancies were included, two pregnancies were expected per woman at age of 50 years, irrespective of a NF1 diagnosis. The hazard of a pregnancy did not differ between women with NF1 (HR 1.03; 95% CI 0.95 to 1.11) and the comparisons after adjustment for somatic and psychiatric disease. The proportion of pregnancies that resulted in a live birth was 63% (783/1252) among women NF1 and 68% (8432/12 465) among the comparisons, yielding a PR of 0.95 (95% CI 0.90 to 1.00). The proportions of stillbirths (PR 2.83; 95% CI 1.63 to 4.93) and spontaneous abortions (PR 1.40; 95% CI 1.09 to 1.79) were increased in women with NF1., Conclusions: A similar hazard for pregnancy was observed for women with NF1 and population comparisons after adjustment for potential medical consequences of NF1. However, women with NF1 experienced more spontaneous abortions and stillbirths., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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23. Systematic Review: Sleep Disorders Based on Objective Data in Children and Adolescents Treated for a Brain Tumor.
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Helligsoe ASL, Weile KS, Kenborg L, Henriksen LT, Lassen-Ramshad Y, Amidi A, Wu LM, Winther JF, Pickering L, and Mathiasen R
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Background: Tumors of the central nervous system (CNS) are the most common solid childhood malignancy. Over the last decades, treatment developments have strongly contributed to the improved overall 5-year survival rate, which is now approaching 75%. However, children now face significant long-term morbidity with late-effects including sleep disorders that may have detrimental impact on everyday functioning and quality of life. The aims of this study were to (1) describe the symptoms that lead to polysomnographic evaluation; (2) describe the nature of sleep disorders diagnosed in survivors of childhood CNS tumor using polysomnography (PSG); and (3) explore the association between tumor location and diagnosed sleep disorder., Methods: An extensive literature search following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA) was conducted. Inclusion criteria were children and adolescents diagnosed with a CNS tumor age <20 years having a PSG performed after end of tumor treatment. The primary outcome was sleep disorder confirmed by PSG., Results: Of the 1,658 studies identified, 11 met the inclusion criteria. All the included articles were appraised for quality and included in the analysis. Analyses indicated that sleep disorders commonly occur among childhood CNS tumor survivors. Symptoms prior to referral for PSG were excessive daytime sleepiness (EDS), fatigue, irregular breathing during sleep and snoring. The most common sleep disorders diagnosed were sleep-related breathing disorders (i.e., obstructive sleep apnea) and central disorders of hypersomnolence (i.e., narcolepsy)., Conclusion: Our findings point to the potential benefit of systematically registering sleep disorder symptoms among CNS tumor patients together with tumor type and treatment information, so that at-risk patients can be identified early. Moreover, future rigorous and larger scale controlled observational studies that include possible modifiable confounders of sleep disorders such as fatigue and obesity are warranted., Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021243866, identifier [CRD42021243866]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Helligsoe, Weile, Kenborg, Henriksen, Lassen-Ramshad, Amidi, Wu, Winther, Pickering and Mathiasen.)
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- 2022
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24. Incidence and survival of childhood central nervous system tumors in Denmark, 1997-2019.
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Helligsoe ASL, Kenborg L, Henriksen LT, Udupi A, Hasle H, and Winther JF
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- Adolescent, Age Distribution, Central Nervous System Neoplasms pathology, Central Nervous System Neoplasms therapy, Child, Child, Preschool, Denmark epidemiology, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Registries, Survival Rate, Central Nervous System Neoplasms epidemiology, Central Nervous System Neoplasms mortality
- Abstract
Background: Incidence rates in Denmark of central nervous system (CNS) tumors remain among the highest in the world. Survival rates, however, have improved in the past decades in high-income countries., Methods: We analyzed incidence and survival of childhood CNS tumors in Denmark diagnosed from 1997 to 2019 based on data from the Danish Childhood Cancer Registry and information on histological types, tumor localization, and treatment from medical records., Results: From 1997 to 2019, 949 children<15 years were diagnosed with a CNS tumor. Age-standardized incidence was 42.1 (95% CI, 39.4-44.6) per million person-years and stable during this period. Age-specific incidence for children aged 0-4 years was 47.7 per million. More than one-third (n = 374, 39.4%) were treated with surgery alone. Overall survival rates 5 and 10 years after diagnosis were 77.6% (95% CI, 74.7-80.2) and 74.7% (95% CI, 71.7-77.5). Five-year overall survival improved from 73.0% (95% CI, 68.9-76.7) in 1997-2008 to 83.2% (95% CI, 79.2-86.4) in 2009-2019 (p-value < 0.0001) in children aged 0-4 years (p = 0.0006)., Conclusion: Incidence rates are stable but remain among the highest in the world. Despite improved survival rates in recent years in younger children, some subtypes still have a poor prognosis., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2022
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25. Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme.
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Frederiksen LE, Erdmann F, Mader L, Mogensen H, Pedersen C, Kenborg L, Bautz A, Talbäck M, Hirvonen E, Nielsen TT, Andersen EAW, Holmqvist AS, Jørgensen OS, Jepsen JRM, Malila N, Hasle H, Madanat-Harjuoja L, Feychting M, and Winther JF
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- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Denmark epidemiology, Female, Finland epidemiology, Humans, Infant, Male, Middle Aged, Siblings, Sweden epidemiology, Young Adult, Cancer Survivors statistics & numerical data, Hospitals, Psychiatric statistics & numerical data, Mental Disorders epidemiology, Psychiatric Department, Hospital statistics & numerical data, Registries statistics & numerical data
- Abstract
Background: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population., Methods: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer., Findings: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals., Interpretation: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors., Funding: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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26. Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark: A nationwide register-based cohort study.
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Kenborg L, Andersen EW, Duun-Henriksen AK, Jepsen JRM, Doser K, Dalton SO, Bidstrup PE, Krøyer A, Frederiksen LE, Johansen C, Østergaard JR, Hove H, Sørensen SA, Riccardi VM, Mulvihill JJ, and Winther JF
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- Attention Deficit Disorder with Hyperactivity complications, Attention Deficit Disorder with Hyperactivity epidemiology, Attention Deficit Disorder with Hyperactivity physiopathology, Autism Spectrum Disorder complications, Autism Spectrum Disorder epidemiology, Autism Spectrum Disorder physiopathology, Child, Child, Preschool, Denmark epidemiology, Depressive Disorder complications, Depressive Disorder epidemiology, Depressive Disorder physiopathology, Female, Humans, Infant, Intellectual Disability complications, Intellectual Disability epidemiology, Intellectual Disability physiopathology, International Classification of Diseases standards, Male, Mental Disorders complications, Mental Disorders physiopathology, Neurofibromatosis 1 complications, Neurofibromatosis 1 physiopathology, Proportional Hazards Models, Psychotic Disorders complications, Psychotic Disorders pathology, Risk Factors, Schizophrenia complications, Schizophrenia epidemiology, Schizophrenia physiopathology, Treatment Outcome, Mental Disorders epidemiology, Neurofibromatosis 1 epidemiology, Psychotic Disorders epidemiology
- Abstract
The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81-9.69) and boys with NF1 (5.02, 95% CI 3.27-7.69) <7 years of age than in the population comparisons. Both sexes had increased HRs for developmental disorders, including attention deficit/hyperactivity disorders, autism spectrum disorders, and intellectual disabilities in childhood. Females with NF1 had also increased HRs for unipolar depression, other emotional and behavioral disorders, and severe stress reaction and adjustment disorders in early adulthood. The HRs for psychoses, schizophrenia, bipolar disorders, and substance abuse were similar in individuals with NF1 and the population comparisons. Finally, the cumulative incidence of a first hospital contact due to any psychiatric disorder by age 30 years was 35% (95% CI 29-41) in females and 28% (95% CI 19-37) in males with NF1. Thus, screening for psychiatric disorders may be important for early diagnosis and facilitation of appropriate and effective treatment in individuals with NF1., (© 2021 Wiley Periodicals LLC.)
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- 2021
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27. Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.
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Licht SF, Rugbjerg K, Andersen EW, Nielsen TT, Norsker FN, Kenborg L, Holmqvist AS, Madanat-Harjuoja LM, Tryggvadottir L, Stovall M, Wesenberg F, Hjorth L, Hasle H, and Winther JF
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- Adult, Child, Female, Humans, Live Birth epidemiology, Pregnancy, Probability, Scandinavian and Nordic Countries epidemiology, Survivors, Cancer Survivors, Neoplasms epidemiology, Neoplasms therapy
- Abstract
Background: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births., Methods: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades., Results: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97])., Conclusions: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary., Lay Summary: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child., (© 2021 American Cancer Society.)
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- 2021
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28. Somatic Disease in Survivors of Childhood Malignant Bone Tumors in the Nordic Countries.
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Pedersen C, Rechnitzer C, Andersen EAW, Kenborg L, Norsker FN, Bautz A, Baad-Hansen T, Tryggvadottir L, Madanat-Harjuoja LM, Holmqvist AS, Hjorth L, Hasle H, Winther JF, and On Behalf Of The ALiCCS Study Group
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Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943-2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76-2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41-1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.
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- 2021
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29. Factors influencing participation rates in clinical late-effect studies of childhood cancer survivors.
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Helligsoe ASL, Henriksen LT, Kenborg L, Dehlendorff C, Winther JF, and Hasle H
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- Child, Disease Progression, Follow-Up Studies, Humans, Survivors, Cancer Survivors, Central Nervous System Neoplasms therapy, Hematologic Neoplasms therapy, Neoplasms therapy
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To ensure external validation of a study population in clinical late-effect studies of childhood cancer, the participation rate must be high. This study investigated demographic data in Nordic late-effect studies and potential factors impacting participation rates such as cancer type, time since diagnosis, and duration of clinical examinations. We found 80 published studies originating from 16 cohorts, with median follow-up of 6.0 years (range 3-14). The overall participation rates ranged from 27% to 100%. The highest participation rates were seen in studies of survivors with solid tumors (92%) and the lowest in hematologic malignancies (67%) and central nervous system tumors (73%). The clinical examination in 10 studies (62.5%) lasted for more than 3 hours. Neither duration of the clinical examination nor time since diagnosis seemed to affect the participation rate. We encourage future studies to describe the recruitment process more thoroughly to improve understanding of the factors influencing participation rates., (© 2021 Wiley Periodicals LLC.)
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- 2021
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30. Late Effects in Childhood Cancer Survivors: Early Studies, Survivor Cohorts, and Significant Contributions to the Field of Late Effects.
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Norsker FN, Pedersen C, Armstrong GT, Robison LL, McBride ML, Hawkins M, Kuehni CE, de Vathaire F, Berbis J, Kremer LC, Haupt R, Kenborg L, and Winther JF
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- Humans, Publishing, Biomedical Research, Cancer Survivors
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With improvement in cure of childhood cancer came the responsibility to investigate the long-term morbidity and mortality associated with the treatments accountable for this increase in survival. Several large cohorts of childhood cancer survivors have been established throughout Europe and North America to facilitate research on long-term complications of cancer treatment. The cohorts have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among childhood cancer survivors, which has been translated into the design of new treatment protocols for pediatric cancers, with the goal to reduce the potential risk and severity of late effects., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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31. Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the European PanCareLIFE cohort study.
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Langer T, Clemens E, Broer L, Maier L, Uitterlinden AG, de Vries ACH, van Grotel M, Pluijm SFM, Binder H, Mayer B, von dem Knesebeck A, Byrne J, van Dulmen-den Broeder E, Crocco M, Grabow D, Kaatsch P, Kaiser M, Spix C, Kenborg L, Winther JF, Rechnitzer C, Hasle H, Kepak T, van der Kooi AF, Kremer LC, Kruseova J, Bielack S, Sorg B, Hecker-Nolting S, Kuehni CE, Ansari M, Kompis M, van der Pal H, Parfitt R, Deuster D, Matulat P, Tillmanns A, Tissing WJE, Beck JD, Elsner S, Am Zehnhoff-Dinnesen A, van den Heuvel-Eibrink MM, and Zolk O
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- Adolescent, Age of Onset, Child, Child, Preschool, Cross-Sectional Studies, Europe, Female, Genetic Association Studies, Genetic Predisposition to Disease, Hearing Loss, Sensorineural chemically induced, Hearing Loss, Sensorineural physiopathology, Humans, Infant, Infant, Newborn, Male, Ototoxicity, Pharmacogenomic Testing, Prospective Studies, Retrospective Studies, Risk Assessment, Risk Factors, Antineoplastic Agents adverse effects, Cancer Survivors, Carboplatin adverse effects, Cisplatin adverse effects, Hearing drug effects, Hearing Loss, Sensorineural genetics, Neoplasms drug therapy, Organic Cation Transporter 2 genetics, Pharmacogenomic Variants, Polymorphism, Single Nucleotide
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Background: Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic markers., Methods: Eligibility criteria required patients to be aged less than 19 years at the start of chemotherapy, which had to include cisplatin and/or carboplatin. Patients were assigned to three phenotype categories: no, minor and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1 and ACYP2) were investigated. Multinomial logistic regression was performed to model the relationship between genetic predictors and platinum ototoxicity, adjusting for clinical risk factors. Additionally, measures of the diagnostic accuracy of the genetic markers were determined., Results: 900 patients were included in this study. In the multinomial logistic regression, significant unique contributions were found from SLC22A2 rs316019, the age at the start of platinum treatment, cranial radiation and the interaction term [platinum compound]∗[cumulative dose of cisplatin]. The predictive performance of the genetic markers was poor compared with the clinical risk factors., Conclusions: PanCareLIFE is the largest study of cisplatin-induced ototoxicity to date and confirmed a role for the polyspecific organic cation transporter SLC22A2. However, the predictive value of the current genetic candidate markers for clinical use is negligible, which puts the value of clinical factors for risk assessment of cisplatin-induced ototoxicity back into the foreground., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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32. Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset.
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Langer T, Clemens E, Broer L, Maier L, Uitterlinden AG, de Vries ACH, van Grotel M, Pluijm SFM, Binder H, Mayer B, von dem Knesebeck A, Byrne J, van Dulmen-den Broeder E, Crocco M, Grabow D, Kaatsch P, Kaiser M, Spix C, Kenborg L, Winther JF, Rechnitzer C, Hasle H, Kepak T, van der Kooi AF, Kremer LC, Kruseova J, Bielack S, Sorg B, Hecker-Nolting S, Kuehni CE, Ansari M, Kompis M, van der Pal HJ, Parfitt R, Deuster D, Matulat P, Tillmanns A, Tissing WJE, Beck JD, Elsner S, Am Zehnhoff-Dinnesen A, van den Heuvel-Eibrink MM, and Zolk O
- Abstract
Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase ( TPMT ) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes ( ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2 ) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Authors.)
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- 2020
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33. Forming and ending marital or cohabiting relationships in a Danish population-based cohort of individuals with neurofibromatosis 1.
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Kjaer TK, Andersen EW, Olsen M, Kenborg L, Bidstrup PE, Doser K, Hove H, Østergaard JR, Johansen C, Sørensen SA, Mulvihill JJ, Winther JF, and Dalton SO
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- Adolescent, Adult, Denmark, Divorce statistics & numerical data, Female, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Neurofibromatosis 1 psychology, Marriage statistics & numerical data, Neurofibromatosis 1 epidemiology
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Individuals with neurofibromatosis 1 (NF1) may have problems in managing the transition between childhood and adulthood, such as forming a relationship or finding a partner. We aimed to determine the association between NF1 and forming and ending marital or cohabiting relationships by comparing a large Danish population of adults with NF1 with population comparisons. In this population-based cohort study, we compared a population of Danish adults who were hospitalized for or with complications to prior diagnosed NF1 (n = 787) with population comparisons matched on gender and birth year (n = 7787) through nationwide registries with annually updated information on marriage and cohabitation. Discrete-time survival models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the formation and termination of relationships, with adjustment for birth year, gender, and somatic and psychiatric comorbidities at entry. Individuals with NF1 were significantly less likely to form a relationship (HR = 0.65; 95% CI: 0.58-0.73), with the lowest association for individuals ≥33 years (HR 0.40; 95% CI: 0.25-0.63) and the highest for those aged 18-20 years (HR 0.82; 95% CI: 0.70-0.96). No significant difference was found for ending relationships (HR 1.00; 95% CI: 0.86-1.16). In conclusion, individuals who were hospitalized for NF1 are less likely to engage in marital or cohabiting relationships than population comparisons and are older when they form their first relationship. Once a relationship has been established, however, couples with a NF1-individual are not at greater risk of ending the relationship.
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- 2020
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34. Clinical characteristics and quality of life, depression, and anxiety in adults with neurofibromatosis type 1: A nationwide study.
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Doser K, Andersen EW, Kenborg L, Dalton SO, Jepsen JRM, Krøyer A, Østergaard J, Hove H, Sørensen SA, Johansen C, Mulvihill J, Winther JF, and Bidstrup PE
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- Adolescent, Adult, Aged, Anxiety epidemiology, Anxiety psychology, Cross-Sectional Studies, Denmark epidemiology, Depression epidemiology, Depression psychology, Female, Humans, Male, Middle Aged, Neurofibromatosis 1 etiology, Prevalence, Young Adult, Anxiety etiology, Depression etiology, Neurofibromatosis 1 psychology, Quality of Life psychology
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Neurofibromatosis type 1 (NF1) is a genetic condition characterized by numerous somatic manifestations. The psychosocial burden in adults has rarely been studied. We examined the prevalence of self-reported impairment of quality of life (QoL), symptoms of anxiety and depression and need for support, associated with disease severity and visibility. We conducted a nationwide cross-sectional study of all 467 adults with NF1 diagnosed between 1977 and 2016 at one of the two national centers for rare diseases in Denmark. A total of 244 (56% response rate) completed a questionnaire that included standard measures of QoL, symptoms of depression and anxiety, indicators of disease-related severity, visibility, and need for professional support. Associations between disease severity and visibility and psychosocial burden were analyzed in descriptive and multivariate models. We observed impaired QoL (mean = 81.3; 95% CI, 76.2; 86.4); 19% reported symptoms of depression (mean = 5.7; SD = 5.4), and 15% reported anxiety (mean = 5.1; SD = 5.2) at a clinical level. Adults with NF1 also reported requiring professional support for physical, psychological, and work-related problems. Disease severity and (partly) visibility were significantly (p < .0001) associated with psychosocial well-being and a requirement for support. This study provides new understanding of the factors associated with impaired QoL, indicating that follow-up care should be optimized into adult life., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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35. Multisystem burden of neurofibromatosis 1 in Denmark: registry- and population-based rates of hospitalizations over the life span.
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Kenborg L, Duun-Henriksen AK, Dalton SO, Bidstrup PE, Doser K, Rugbjerg K, Pedersen C, Krøyer A, Johansen C, Andersen KK, Østergaard JR, Hove H, Sørensen SA, Riccardi VM, Mulvihill JJ, and Winther JF
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- Adult, Child, Denmark epidemiology, Hospitalization, Humans, Longevity, Registries, Neurofibromatosis 1 diagnosis, Neurofibromatosis 1 epidemiology
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Purpose: The aim was to assess lifetime risk for hospitalization in individuals with neurofibromatosis 1 (NF1)., Methods: The 2467 individuals discharged with a diagnosis indicating NF1 or followed in a clinical center for NF1 were matched to 20,132 general population comparisons. Based on diagnoses in 12 main diagnostic groups and 146 subcategories, we calculated rate ratios (RRs), absolute excess risks (AERs), and hazard ratios for hospitalizations., Results: The RR for any first hospitalization among individuals with NF1 was 2.3 (95% confidence interval 2.2-2.5). A high AER was seen for all 12 main diagnostic groups, dominated by disorders of the nervous system (14.5% of all AERs), benign (13.6%) and malignant neoplasms (13.4%), and disorders of the digestive (10.5%) and respiratory systems (10.3%). Neoplasms, nerve and peripheral ganglia disease, pneumonia, epilepsy, bone and joint disorders, and intestinal infections were major contributors to the excess disease burden caused by NF1. Individuals with NF1 had more hospitalizations and spent more days in hospital than the comparisons. The increased risk for any hospitalization was observed for both children and adults, with or without an associated cancer., Conclusion: NF1 causes an overall greater likelihood of hospitalization, with frequent and longer hospitalizations involving all organ systems throughout life.
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- 2020
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36. Genetic variation of cisplatin-induced ototoxicity in non-cranial-irradiated pediatric patients using a candidate gene approach: The International PanCareLIFE Study.
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Clemens E, Broer L, Langer T, Uitterlinden AG, de Vries ACH, van Grotel M, Pluijm SFM, Binder H, Byrne J, Broeder EVD, Crocco M, Grabow D, Kaatsch P, Kaiser M, Kenborg L, Winther JF, Rechnitzer C, Hasle H, Kepak T, van der Kooi AF, Kremer LC, Kruseova J, Kuehni CE, van der Pal H, Parfitt R, Deuster D, Matulat P, Spix C, Tillmanns A, Tissing WJE, Maier L, Am Zehnhoff-Dinnesen A, Zolk O, and van den Heuvel-Eibrink MM
- Subjects
- Adolescent, Child, Child, Preschool, Female, Hearing Loss chemically induced, Hearing Loss epidemiology, Hearing Loss genetics, Humans, Infant, Infant, Newborn, Male, Neoplasms drug therapy, Neoplasms epidemiology, Neoplasms genetics, Ototoxicity epidemiology, Retrospective Studies, Young Adult, Antineoplastic Agents adverse effects, Cisplatin adverse effects, Genetic Association Studies methods, Genetic Variation genetics, Internationality, Ototoxicity genetics
- Abstract
Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8-21.5; P = 5.6 × 10
-7 ) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2 : OR: 2.4; 95% CI: 1.3-4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04-14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07-2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.- Published
- 2020
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37. Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study.
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Kenborg L, Linnet KM, de Fine Licht S, Bautz A, Holmqvist AS, Tryggvadottir L, Madanat-Harjuoja LM, Stovall M, Heilmann C, Albieri V, Hasle H, and Winther JF
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Nervous System Diseases etiology, Nervous System Diseases therapy, Nervous System Neoplasms mortality, Registries statistics & numerical data, Retrospective Studies, Risk Assessment statistics & numerical data, Scandinavian and Nordic Countries epidemiology, Young Adult, Cancer Survivors statistics & numerical data, Hospitalization statistics & numerical data, Nervous System Diseases epidemiology, Nervous System Neoplasms complications
- Abstract
Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943-2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9-2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2-5.3) and leukemia (2.8; 95% CI 2.4-3.2). The AER decreased from 331 (278-383) excess neurologic disorders per 100,000 person-years 5-9 years after diagnosis to 82 (46-118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed., (© 2019 UICC.)
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- 2020
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38. Neurologic disorders in long-term survivors of neuroblastoma - a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program.
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Norsker FN, Rechnitzer C, Andersen EW, Linnet KM, Kenborg L, Holmqvist AS, Tryggvadottir L, Madanat-Harjuoja LM, Øra I, Thorarinsdottir HK, Vettenranta K, Bautz A, Schrøder H, Hasle H, and Winther JF
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- Adolescent, Adult, Child, Follow-Up Studies, Hospitalization, Humans, Incidence, Nervous System Diseases pathology, Neuroblastoma complications, Neuroblastoma therapy, Registries statistics & numerical data, Risk, Scandinavian and Nordic Countries epidemiology, Young Adult, Cancer Survivors statistics & numerical data, Nervous System Diseases epidemiology, Nervous System Diseases etiology, Neuroblastoma epidemiology
- Abstract
Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma. Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959-2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors. Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7-3.6) and an AER of 16 per 1,000 person-years (95% CI 12-19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma. Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.
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- 2020
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39. Correction: Educational delay and attainment in persons with neurofibromatosis 1 in Denmark.
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Doser K, Kenborg L, Andersen EW, Bidstrup PE, Kroyer A, Hove H, Østergaard J, Sørensen SA, Johansen C, Mulvihill J, Winther JF, and Dalton SO
- Abstract
Since the publication of the article, the authors noticed that 'NFI cohort' and 'NFI-free cohort' columns in the 'Autism
g' and the 'Autism/ADHD' rows had been erroneously interchanged in Table 3. This has now been updated in the HTML and PDF of the original article.- Published
- 2019
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40. Educational delay and attainment in persons with neurofibromatosis 1 in Denmark.
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Doser K, Kenborg L, Andersen EW, Bidstrup PE, Kroyer A, Hove H, Østergaard J, Sørensen SA, Johansen C, Mulvihill J, Winther JF, and Dalton SO
- Subjects
- Adolescent, Adult, Child, Cohort Studies, Denmark, Female, Humans, Male, Middle Aged, Cognition, Education, Neurofibromatosis 1, Registries, Schools
- Abstract
Most research on psychosocial consequences of neurofibromatosis type 1 (NF1) has focused on the relationship between disease factors and cognitive functioning. NF1 may impair domains of learning and attention, resulting in low academic performance. This study is the first nationwide population-based cohort study to investigate educational attainment and delay in completing mandatory school by persons with NF1. Educational information was collected from 550 persons at the age of 30 (born 1965-1984). They were diagnosed with NF1 in Denmark and compared to a cohort of NF1-free persons matched on gender and age (n = 4295). Multinomial logistic models were applied to estimate odds ratios (ORs) for obtaining short (≤9 years) or medium (10-12 years) education compared to long education (>12 years) by the age of 30 years. We calculated the probability of graduating 9
th year of mandatory school at different ages in 932 persons with NF1 and 7962 NF1-free persons (born 1965-2000) using quantile regression. The OR of educational completion for short- and medium-term education was three fold (95% CI 2.55-3.99) and 1.29 fold (95% CI 0.99-1.69) higher, respectively, for persons with NF1 than NF1-free persons after adjusting for birth year, gender, psychiatric and somatic morbidity and mother's education. Persons with NF1 were significantly delayed in graduating mandatory school education compared to NF1-free persons. When 90% of persons have graduated, persons with NF1 were 1.2 times older than the NF1-free persons. Experiencing delays in mandatory school likely affect further educational achievements and may impair employment and entering work force.- Published
- 2019
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41. Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study.
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Clemens E, Meijer AJ, Broer L, Langer T, van der Kooi AL, Uitterlinden AG, de Vries A, Kuehni CE, Garrè ML, Kepak T, Kruseova J, Winther JF, Kremer LC, van Dulmen-den Broeder E, Tissing WJ, Rechnitzer C, Kenborg L, Hasle H, Grabow D, Parfitt R, Binder H, Carleton BC, Byrne J, Kaatsch P, Am Zehnhoff-Dinnesen A, Zolk O, and van den Heuvel-Eibrink MM
- Abstract
Background: Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common adverse effect in children treated with cisplatin-based chemotherapy or cranial radiotherapy. Ototoxicity can extend from high-tone hearing impairment to involvement of speech frequencies. Hearing impairment can impede speech and language and neurocognitive development. Although treatment-related risk factors for hearing loss following childhood cancer treatment have been identified, the individual variability in toxicity of adverse effects after similar treatment between childhood cancer patients suggests a role for genetic susceptibility. Currently, 12 candidate gene approach studies have been performed to identify polymorphisms predisposing to platinum-induced ototoxicity in children being treated for cancer. However, results were inconsistent and most studies were underpowered and/or lacked replication., Objective: We describe the design of the PanCareLIFE consortium's work packages that address the genetic susceptibility of platinum-induced ototoxicity., Methods: As a part of the PanCareLIFE study within the framework of the PanCare consortium, we addressed genetic susceptibility of treatment-induced ototoxicity during and after childhood cancer treatment in a large European cohort by a candidate gene approach and a genome-wide association screening., Results: This study included 1124 survivors treated with cisplatin, carboplatin, or cranial radiotherapy for childhood cancer, resulting in the largest clinical European cohort assembled for this late effect to date. Within this large cohort we defined a group of 598 cisplatin-treated childhood cancer patients not confounded by cranial radiotherapy. The PanCareLIFE initiative provided, for the first time, a unique opportunity to confirm already identified determinants for hearing impairment during childhood cancer using a candidate gene approach and set up the first international genome-wide association study of cisplatin-induced direct ototoxicity in childhood cancer patients to identify novel allelic variants. Results will be validated in an independent replication cohort. Patient recruitment started in January 2015 and final inclusion was October 2017. We are currently performing the analyses and the first results are expected by the end of 2019 or the beginning of 2020., Conclusions: Genetic factors identified as part of this pan-European project, PanCareLIFE, may contribute to future risk prediction models that can be incorporated in future clinical trials of platinum-based therapies for cancer and may help with the development of prevention strategies., International Registered Report Identifier (irrid): DERR1-10.2196/11868., (©Eva Clemens, Annelot JM Meijer, Linda Broer, Thorsten Langer, Anne-Lotte LF van der Kooi, André G Uitterlinden, Andrica de Vries, Claudia E Kuehni, Maria L Garrè, Tomas Kepak, Jarmila Kruseova, Jeanette F Winther, Leontien C Kremer, Eline van Dulmen-den Broeder, Wim JE Tissing, Catherine Rechnitzer, Line Kenborg, Henrik Hasle, Desiree Grabow, Ross Parfitt, Harald Binder, Bruce C Carleton, Julianne Byrne, Peter Kaatsch, Antoinette am Zehnhoff-Dinnesen, Oliver Zolk, Marry M van den Heuvel-Eibrink. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 19.03.2019.)
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- 2019
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42. Neurologic disorders in 4858 survivors of central nervous system tumors in childhood-an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study.
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Kenborg L, Winther JF, Linnet KM, Krøyer A, Albieri V, Holmqvist AS, Tryggvadottir L, Madanat-Harjuoja LM, Stovall M, Hasle H, and Olsen JH
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Nervous System Diseases pathology, Prognosis, Risk Factors, Scandinavian and Nordic Countries epidemiology, Survival Rate, Young Adult, Cancer Survivors statistics & numerical data, Central Nervous System Neoplasms complications, Hospitalization statistics & numerical data, Nervous System Diseases epidemiology, Nervous System Diseases etiology, Registries statistics & numerical data
- Abstract
Background: A comprehensive overview of neurologic complications among survivors of central nervous system (CNS) tumors in childhood is lacking. We aimed to investigate the risk for these disorders in a large, population-based study with outcome measures from nationwide hospital registries., Methods: We identified 4858 five-year survivors with diagnoses of CNS tumor in childhood in Denmark, Iceland, Finland, and Sweden in 1943-2007, and 166658 matched population comparison subjects. Inpatient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs)., Results: A neurologic disorder was verified in 1309 survivors, while 92.4 were expected, yielding an overall RR of 14.2 (95% confidence interval [CI]: 13.3-15.1) and an AER of 20 hospitalizations per 1000 persons per year. The risks remained increased more than 20 years after diagnosis (RR: 6.3, 95% CI: 5.6-7.2; AER: 11, 9-12). The most frequent diagnoses were epilepsy (affecting 14.1% of all survivors) followed by hydrocephalus (9.5%) and paralytic syndromes (4.2%), with RRs of 28.7 (95% CI: 26.0-31.6), 243 (95% CI: 190-311), and 40.3 (95% CI: 33.1-49.2), respectively. Of these outcomes, 30%-40% were diagnosed prior to or synchronously with the CNS tumor. The survivors had highly increased RRs for infectious diseases of the CNS, disorders of cranial nerves, and degenerative diseases of the nervous system., Conclusions: Survivors of childhood CNS tumors are at markedly increased risk for neurologic disorders throughout their lives. Health care professionals must be aware of survivors who might benefit from preventive interventions and intensive follow-up.
- Published
- 2019
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43. PanCareLIFE: The scientific basis for a European project to improve long-term care regarding fertility, ototoxicity and health-related quality of life after cancer occurring among children and adolescents.
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Byrne J, Grabow D, Campbell H, O'Brien K, Bielack S, Am Zehnhoff-Dinnesen A, Calaminus G, Kremer L, Langer T, van den Heuvel-Eibrink MM, van Dulmen-den Broeder E, Baust K, Bautz A, Beck JD, Berger C, Binder H, Borgmann-Staudt A, Broer L, Cario H, Casagranda L, Clemens E, Deuster D, de Vries A, Dirksen U, Winther JF, Fosså S, Font-Gonzalez A, Grandage V, Haupt R, Hecker-Nolting S, Hjorth L, Kaiser M, Kenborg L, Kepak T, Kepáková K, Knudsen LE, Krawczuk-Rybak M, Kruseova J, Kuehni CE, Kunstreich M, Kuonen R, Lackner H, Leiper A, Loeffen EAH, Luks A, Modan-Moses D, Mulder R, Parfitt R, Paul NW, Ranft A, Ruud E, Schilling R, Spix C, Stefanowicz J, Strauβ G, Uitterlinden AG, van den Berg M, van der Kooi AL, van Dijk M, van Leeuwen F, Zolk O, Zöller D, and Kaatsch P
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Europe, Feasibility Studies, Female, Fertility Preservation, Humans, Infant, Infant, Newborn, Long-Term Care, Male, Neoplasms, Pilot Projects, Survivors, Young Adult, Quality of Life psychology
- Abstract
Aims: Survival after cancer diagnosed during childhood or adolescence continues to improve with new treatments and supportive therapies. Optimal long-term care requires that risks to vulnerable organs are clearly defined and translated into guidelines that are implemented into practice. PanCareLIFE is a pan-European consortium that addresses survivorship issues comprising fertility, hearing impairment and quality of life. This article describes the scientific basis of PanCareLIFE's studies., Methods: PanCareLIFE involves 17 partner institutions from eight European countries, with additional 11 data providers from five other countries. Study designs and methods include molecular genetic, cohort and case-control studies, a longitudinal study and an intervention study. Ethics and data protection issues have been taken into account from the beginning., Results: PanCareLIFE will investigate the way that treatment impairs female fertility, by evaluating anti-Müllerian hormone levels and the underlying genetic susceptibility to loss of fertility. For our fertility studies, more than 6000 survivors have completed questionnaires, more than 1500 provided serum samples and more than 400 case-control triads have been identified. Fertility preservation guidelines for boys and girls will be developed. More than 2000 survivors have contributed audiograms for the ototoxicity study. Almost 1000 samples were sent for genetic analysis related to ototoxicity and gonadal reserve. The SF-36 questionnaire will measure quality of life in more than 10,000 survivors., Conclusions: The large number of subjects enrolled in PanCareLIFE and the detailed information accumulated will allow in-depth evaluation of important outcomes. Fertility preservation guidelines will help patients and their families make informed decisions and contribute to their long-term well-being., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
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- 2018
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44. Pre-diagnostic changes in body mass index and mortality among breast cancer patients.
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Larsen SB, Torstensson M, Kenborg L, Christensen J, Kroman N, Dalton SO, Tjønneland A, Johansen C, and Bidstrup PE
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- Adult, Aged, Body Weight, Breast Neoplasms diagnosis, Breast Neoplasms mortality, Breast Neoplasms therapy, Denmark epidemiology, Disease Management, Female, Humans, Middle Aged, Mortality, Prognosis, Proportional Hazards Models, Public Health Surveillance, Registries, Risk Factors, Young Adult, Body Mass Index, Breast Neoplasms epidemiology
- Abstract
Purpose: We investigated whether changes in body mass index (BMI) before a breast cancer diagnosis affected mortality and whether trajectories more accurately predict overall mortality compared to a single measure of BMI., Methods: Our prospective cohort comprised 2012 women with breast cancer who reported their weight in each decade from 20 to 50-64 years of age. We used trajectory analysis to identify groups with similar development patterns in BMI and Cox proportional hazards models to examine the association between trajectory groups and mortality, and interactions with oestrogen receptor status and smoking. We used c-index statistics to compare the trajectory model with the single measure model of BMI., Results: We identified three distinct trajectory groups, with a mean BMI at age 20 of 19, 22 and 24 increasing to 23 (normal-to-normal), 29 (normal-to-overweight) and 37 (normal-to-obese) at 50-64 years of age, respectively. Women in the normal-to-obese trajectory group experienced significantly higher overall mortality than those in the normal-to-normal trajectory group (HR 1.76, 95% CI 1.21‒2.56). The association declined to a non-significant level after adjustments for clinical prognostic factors. Although not significant, the same tendency was seen for breast cancer-specific mortality. The association was strongest in women with oestrogen receptor-negative tumours. Weight changes over time were not significantly different from a single BMI measure before diagnosis to predict survival., Conclusion: Weight gain affects overall mortality after breast cancer but clinical prognostic factors largely eliminate the association. Using trajectories of weight changes did not improve the predictive value compared to a single measure of BMI.
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- 2018
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45. Does vagotomy reduce the risk of Parkinson's disease?
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Tysnes OB, Kenborg L, Herlofson K, Steding-Jessen M, Horn A, Olsen JH, and Reichmann H
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- Female, Humans, Male, Parkinson Disease diagnosis, Parkinson Disease epidemiology, Vagotomy trends
- Published
- 2015
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46. Occupational history of night shift work and Parkinson's disease in Denmark.
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Schernhammer ES, Lassen CF, Kenborg L, Ritz B, Olsen JH, and Hansen J
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- Adult, Aged, Case-Control Studies, Denmark epidemiology, Educational Status, Family Health, Female, Humans, Interviews as Topic, Life Style, Logistic Models, Male, Medical Records, Middle Aged, Residence Characteristics, Risk Factors, Time Factors, Circadian Rhythm physiology, Parkinson Disease epidemiology, Work Schedule Tolerance physiology
- Abstract
Objectives: We investigated whether working night shifts was associated with the risk of Parkinson's disease (PD)., Methods: Between January 2008 and December 2010, we recruited 1808 patients with a confirmed diagnosis of idiopathic PD from Denmark and 1876 population controls matched by year of birth and gender. Information on lifelong occupational history, including information on night work, smoking, caffeine and alcohol consumption habits, and family history of PD was collected through structured telephone interviews., Results: Overall, there was no association between a history of night shift work and PD [odds ratio (OR) for any type of night work (ie, either permanent or rotating night work) 1.01, 95% confidence interval (95% CI) 0.86-1.21]. Compared with persons who never worked night shifts, risks of those with longer durations of night work did not appear to differ (OR <10 years=0.95, 95% CI 0.75-1.19, OR 10-19 years= 1.09, 95% CI 0.77-1.53, OR ≥20 years=1.05, 95% CI 0.81-1.37, P for trend=0.23). Associations were similar among men and women., Conclusions: These data suggest that working night shifts is not associated with PD or that low tolerance for night shift work is an early marker of PD. Due to the novel and exploratory nature of these findings, confirmation is needed.
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- 2015
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47. Lifestyle, family history, and risk of idiopathic Parkinson disease: a large Danish case-control study.
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Kenborg L, Lassen CF, Ritz B, Andersen KK, Christensen J, Schernhammer ES, Hansen J, Wermuth L, Rod NH, and Olsen JH
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Denmark epidemiology, Female, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Parkinson Disease prevention & control, Risk, Alcohol Drinking epidemiology, Caffeine, Parkinson Disease epidemiology, Smoking adverse effects, Smoking epidemiology
- Abstract
The relationship between Parkinson disease (PD) and smoking has been examined in several studies, but little is known about smoking in conjunction with other behaviors and a family history of PD. Using unconditional logistic regression analysis, we studied individual and joint associations of these factors with idiopathic PD among 1,808 Danish patients who were diagnosed in 1996-2009 and matched to 1,876 randomly selected population controls. Although there was a downward trend in duration of smoking, this was not observed for daily tobacco consumption. A moderate intake of caffeine (3.1-5 cups/day) was associated with a lower odds ratio for PD (0.45, 95% confidence interval: 0.34, 0.62), as was a moderate intake of alcohol (3.1-7 units/week) (odds ratio = 0.60, 95% confidence interval: 0.58, 0.84); a higher daily intake did not reduce the odds further. When these behaviors were studied in combination with smoking, the odds ratios were lower than those for each one alone. Compared with never smokers with no family history of PD, never smokers who did have a family history had an odds ratio of 2.81 (95% confidence interval: 1.91, 4.13); for smokers with a family history, the odds ratio was 1.60 (95% confidence interval: 1.15, 2.23). In conclusion, duration of smoking seems to be more important than intensity in the relationship between smoking and idiopathic PD. The finding of lower risk estimates for smoking in combination with caffeine or alcohol requires further confirmation., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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48. Childhood cancer survivor cohorts in Europe.
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Winther JF, Kenborg L, Byrne J, Hjorth L, Kaatsch P, Kremer LC, Kuehni CE, Auquier P, Michel G, de Vathaire F, Haupt R, Skinner R, Madanat-Harjuoja LM, Tryggvadottir L, Wesenberg F, Reulen RC, Grabow D, Ronckers CM, van Dulmen-den Broeder E, van den Heuvel-Eibrink MM, Schindler M, Berbis J, Holmqvist AS, Gudmundsdottir T, de Fine Licht S, Bonnesen TG, Asdahl PH, Bautz A, Kristoffersen AK, Himmerslev L, Hasle H, Olsen JH, and Hawkins MM
- Subjects
- Adolescent, Child, Cohort Effect, Europe epidemiology, Humans, Leukemia therapy, Quality of Health Care, Survival Rate, Needs Assessment, Neoplasms mortality, Neoplasms therapy, Survivors
- Abstract
With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.
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- 2015
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49. Head injury and risk for Parkinson disease: results from a Danish case-control study.
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Kenborg L, Rugbjerg K, Lee PC, Ravnskjær L, Christensen J, Ritz B, and Lassen CF
- Subjects
- Adult, Aged, Aged, 80 and over, Case-Control Studies, Craniocerebral Trauma complications, Denmark epidemiology, Female, Humans, Male, Middle Aged, Parkinson Disease etiology, Risk Factors, Craniocerebral Trauma diagnosis, Craniocerebral Trauma epidemiology, Parkinson Disease diagnosis, Parkinson Disease epidemiology
- Abstract
Objective: To examine the association between head injuries throughout life and the risk for Parkinson disease (PD) in an interview-based case-control study., Methods: We identified 1,705 patients diagnosed with PD at 10 neurologic centers in Denmark in 1996-2009 and verified their diagnoses in medical records. Patients were matched to 1,785 controls randomly selected from the Danish Central Population Register on sex and year of birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression., Results: We observed no association between any head injury before first cardinal symptom and PD (OR 1.02; 95% CI 0.88, 1.19). Examination of number of head injuries (1: OR 1.02; 95% CI 0.87, 1.20; ≥2: OR 1.03; 95% CI 0.72, 1.47) or hospitalization for a head injury (OR 0.89; 95% CI 0.70, 1.12) did not show an association with PD. For 954 study subjects with at least one head injury, there was no evidence of an association between loss of consciousness (OR 0.89; 95% CI 0.67, 1.17), duration of loss of consciousness (≤1 minute: OR 0.93; 95% CI 0.58, 1.49; 1-5 minutes: OR 0.74; 95% CI 0.51, 1.08; ≥5 minutes: OR 0.81; 95% CI 0.53, 1.24), or amnesia (OR 1.31; 95% CI 0.88, 1.95) and risk for PD. Application of a lag time of 10 years between head injury and first cardinal symptom resulted in similar risk estimates., Conclusions: The results do not support the hypothesis that head injury increases the risk for PD., (© 2015 American Academy of Neurology.)
- Published
- 2015
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50. Parkinson's disease and other neurodegenerative disorders among welders: a Danish cohort study.
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Kenborg L, Lassen CF, Hansen J, and Olsen JH
- Subjects
- Adolescent, Adult, Aged, Cohort Studies, Confidence Intervals, Denmark epidemiology, Female, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Neoplasms epidemiology, Occupational Exposure statistics & numerical data, Parkinson Disease etiology, Proportional Hazards Models, Retrospective Studies, Young Adult, Neurodegenerative Diseases epidemiology, Parkinson Disease epidemiology
- Abstract
It has been hypothesized that welders are at increased risk for neurological disorders, including Parkinson's disease, but few well-designed cohort studies have been conducted. The risk for Parkinson's disease and other neurodegenerative disorders was examined in an updated follow-up study based on a previous cohort of 5867 Danish welders and 1735 nonwelding metal workers exposed to welding fume. Occupational history and information on smoking were obtained from questionnaires, supplemented by information from the compulsory Danish Supplementary Pension Fund. Hospital contacts, including outpatient data from 1994, for Parkinson's disease and other neurological disorders were ascertained from the Danish National Hospital Register. Based on first-time hospital contacts, standardized hospitalization ratios (SHRs) were calculated for the entire cohort and for welders, metal workers, and nonresponders separately and for the general Danish population in 1987-2008. In an internal analysis of welders, Cox proportional hazard models were used to estimate hospitalization rate ratios (HRRs) for Parkinson's disease associated with lifelong exposure to welding. Overall, 45 cohort members had a hospital contact for Parkinson's disease (SHR, 1.12; 95% confidence interval [CI], 0.82-1.50), of whom 25 were welders (standardized incidence rate ratio, 1.05; 95% CI, 0.68-1.55). When duration of welding was compared among 5736 welders, the HRR was 0.83 (95% CI, 0.59-1.16) per 10 years' welding, after adjustment for smoking. The results of this study do not support the hypothesis that welders are at increased risk for Parkinson's disease; these findings are consistent with those of our previously published analysis. © 2012 Movement Disorder Society., (Copyright © 2012 Movement Disorder Society.)
- Published
- 2012
- Full Text
- View/download PDF
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