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dc.contributor.authorAl-Jebari, Yahia
dc.contributor.authorGlimelius, Ingrid
dc.contributor.authorNord, Carina Berglund
dc.contributor.authorCohn-Cedermark, Gabriella
dc.contributor.authorStåhl, Olof
dc.contributor.authorTandstad, Torgrim
dc.contributor.authorJensen, Allan
dc.contributor.authorHaugnes, Hege Sagstuen
dc.contributor.authorDaugaard, Gedske
dc.contributor.authorRylander, Lars
dc.contributor.authorGiwercman, Aleksander
dc.date.accessioned2020-01-13T10:05:35Z
dc.date.available2020-01-13T10:05:35Z
dc.date.created2019-07-27T12:19:14Z
dc.date.issued2019
dc.identifier.citationNature Methods. 2019, 16:e1002816 (6), 1-14.nb_NO
dc.identifier.issn1548-7091
dc.identifier.urihttp://hdl.handle.net/11250/2635893
dc.description.abstractBackground Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. Methods and findings In this nationwide register study, all singletons born in Sweden 1994–2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19–1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment–to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54–1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25–4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995–2000—both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. Conclusions No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.nb_NO
dc.language.isoengnb_NO
dc.publisherPublic Library of Sciencenb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleCancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register studynb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber1-14nb_NO
dc.source.volume16:e1002816nb_NO
dc.source.journalNature Methodsnb_NO
dc.source.issue6nb_NO
dc.identifier.doi10.1371/journal.pmed.1002816
dc.identifier.cristin1712941
dc.description.localcodeCopyright: © 2019 Al-Jebari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.nb_NO
cristin.unitcode194,65,15,0
cristin.unitcode1920,12,0,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameKreftklinikken
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2


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