Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register study
| Autor: | Gabriella Cohn-Cedermark, Yahia Al-Jebari, Carina Nord, Hege Sagstuen Haugnes, Torgrim Tandstad, Ingrid Glimelius, Lars Rylander, Gedske Daugaard, Allan Jensen, Aleksander Giwercman, Olof Ståhl |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Pediatrics medicine.medical_treatment Cancer Treatment 030204 cardiovascular system & hematology Geographical locations Nervous System Malformations/chemically induced Fathers 0302 clinical medicine Testicular Neoplasms/drug therapy Testicular Cancer Medicine and Health Sciences 030212 general & internal medicine Registries Child health care economics and organizations Register study Pharmaceutics food and beverages Congenital malformations General Medicine Neoplasms Germ Cell and Embryonal Congenital Anomalies Europe Oncology Medicine Female Research Article Adult Clinical Oncology endocrine system medicine.medical_specialty Urology Cancer therapy Radiation Therapy Antineoplastic Agents Abnormalities Radiation-Induced Nervous System Malformations 03 medical and health sciences Cancer Chemotherapy Testicular Neoplasms Drug Therapy Diagnostic Medicine health services administration medicine Congenital Disorders Cancer Detection and Diagnosis Humans Chemotherapy Abnormalities Radiation-Induced/diagnosis VDP::Medisinske Fag: 700 European Union Testicular cancer Testicular Germ Cell Cancer Sweden Cancer och onkologi business.industry Cancer Cancers and Neoplasms Antineoplastic Agents/adverse effects medicine.disease Radiation therapy VDP::Medical disciplines: 700 Genitourinary Tract Tumors Increased risk Sweden/epidemiology Cancer and Oncology Clinical Medicine People and places business Neoplasms Germ Cell and Embryonal/drug therapy |
| Zdroj: | PLoS Medicine Al-Jebari, Y, Glimelius, I, Berglund Nord, C, Cohn-Cedermark, G, Ståhl, O, Tandstad, T, Jensen, A, Sagstuen Haugnes, H, Daugaard, G, Rylander, L & Giwercman, A 2019, ' Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer : A nationwide register study ', PLoS Medicine, vol. 16, no. 6, e1002816 . https://doi.org/10.1371/journal.pmed.1002816 16:e1002816 Nature Methods PLoS Medicine, Vol 16, Iss 6, p e1002816 (2019) |
| DOI: | 10.1371/journal.pmed.1002816 |
| Popis: | 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. Yahia Al-Jebari and colleagues reveal no increased risk of congenital malformations in children of men treated for testicular germ cell cancer. Author summary Why was this study done? Chemotherapy and radiotherapy have both been shown to cause mutations and genetic damage in animal studies, leading to fears that men being treated with these therapies might be more prone to have children with genetic diseases and birth defects. This study investigates whether receiving treatment for testicular cancer, being the most common cancer among young men (in child-having ages), leads to a higher risk of fathering a child with a birth defect. What did the researchers do and find? By accessing data from Swedish national registries, we gathered data on more than 2 million newborns and their fathers. Among them, 2,380 fathers had testicular cancer and they had, in total, 4,207 children. When comparing the children conceived after the father received cancer treatment to the children born before treatment, we could not find any evidence showing that chemotherapy or radiotherapy leads to an increased risk of birth defects. We did see that there was, irrespectively of cancer treatment, a small risk increase associated with the fathers’ testicular cancer itself, meaning that men with testicular cancer have an approximately 30% higher relative risk of having a child with a birth defect (an increase from 3.5% to 4.4%). What do these findings mean? There was no risk increase due to cancer therapies. The risk increase detected was associated with testicular cancer. However, this risk increase is very small and relates to rare conditions. Because the risk increase is small, we therefore do not consider this cause for concern and wish this reassuring information to be passed on to patients. |
| Databáze: | OpenAIRE |
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