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Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register study
Lund Univ, Mol Reprod Med, Dept Translat Med, Malmo, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Div Clin Epidemiol, Dept Med, Stockholm, Sweden.
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
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2019 (English)In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 16, no 6, article id e1002816Article in journal (Refereed) Published
Abstract [en]

Background 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.

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PUBLIC LIBRARY SCIENCE , 2019. Vol. 16, no 6, article id e1002816
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Cancer and Oncology
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URN: urn:nbn:se:uu:diva-390647DOI: 10.1371/journal.pmed.1002816ISI: 000473778000003PubMedID: 31163029OAI: oai:DiVA.org:uu-390647DiVA, id: diva2:1343773
Funder
Swedish Cancer Society, CAN 2017/413Swedish Childhood Cancer Foundation, KP2018-0020Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2019-08-19Bibliographically approved

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