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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

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Harvard

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, pp. e1002816. https://doi.org/10.1371/journal.pmed.1002816

APA

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, 16(6), e1002816. [e1002816]. https://doi.org/10.1371/journal.pmed.1002816

CBE

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. 16(6):e1002816. https://doi.org/10.1371/journal.pmed.1002816

MLA

Vancouver

Author

Al-Jebari, Yahia ; Glimelius, Ingrid ; Berglund Nord, Carina ; Cohn-Cedermark, Gabriella ; Ståhl, Olof ; Tandstad, Torgrim ; Jensen, Allan ; Sagstuen Haugnes, Hege ; Daugaard, Gedske ; Rylander, Lars ; Giwercman, Aleksander. / Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer : A nationwide register study. In: PLOS Medicine. 2019 ; Vol. 16, No. 6. pp. e1002816.

Bibtex

@article{6196764418fb4a3fb70f6332c3c2d1fd,
title = "Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: A nationwide register study",
abstract = "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.",
author = "Yahia Al-Jebari and Ingrid Glimelius and {Berglund Nord}, Carina and Gabriella Cohn-Cedermark and Olof St{\aa}hl and Torgrim Tandstad and Allan Jensen and {Sagstuen Haugnes}, Hege and Gedske Daugaard and Lars Rylander and Aleksander Giwercman",
year = "2019",
month = jun,
day = "1",
doi = "10.1371/journal.pmed.1002816",
language = "English",
volume = "16",
pages = "e1002816",
journal = "PLOS Medicine",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "6",

}

RIS

TY - JOUR

T1 - Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer

T2 - A nationwide register study

AU - Al-Jebari, Yahia

AU - Glimelius, Ingrid

AU - Berglund Nord, Carina

AU - Cohn-Cedermark, Gabriella

AU - Ståhl, Olof

AU - Tandstad, Torgrim

AU - Jensen, Allan

AU - Sagstuen Haugnes, Hege

AU - Daugaard, Gedske

AU - Rylander, Lars

AU - Giwercman, Aleksander

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85067425101&partnerID=8YFLogxK

U2 - 10.1371/journal.pmed.1002816

DO - 10.1371/journal.pmed.1002816

M3 - Journal article

C2 - 31163029

VL - 16

SP - e1002816

JO - PLOS Medicine

JF - PLOS Medicine

SN - 1549-1277

IS - 6

M1 - e1002816

ER -

ID: 57752075