Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study.
Childhood cancer
birth defects
cancer risk
congenital anomalies
sex differences
Journal
International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871
Informations de publication
Date de publication:
19 04 2023
19 04 2023
Historique:
received:
17
01
2022
accepted:
19
09
2022
medline:
20
4
2023
pubmed:
1
10
2022
entrez:
30
9
2022
Statut:
ppublish
Résumé
Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0-19 years) and 218 980 matched population controls, born 1967-2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6-12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8-2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6-3.1) than males (OR = 2.1, 95% CI = 1.9-2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year). The birth defect-cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.
Sections du résumé
BACKGROUND
Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear.
METHODS
We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0-19 years) and 218 980 matched population controls, born 1967-2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects.
RESULTS
Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6-12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8-2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6-3.1) than males (OR = 2.1, 95% CI = 1.9-2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year).
CONCLUSIONS
The birth defect-cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.
Identifiants
pubmed: 36179253
pii: 6732403
doi: 10.1093/ije/dyac192
pmc: PMC10114053
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
450-465Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.
Références
Birth Defects Res A Clin Mol Teratol. 2011 Oct;91(10):894-901
pubmed: 21987467
BMJ. 2020 Dec 2;371:m4060
pubmed: 33268348
Acta Oncol. 2009;48(1):27-33
pubmed: 18767000
Nat Rev Immunol. 2016 Oct;16(10):626-38
pubmed: 27546235
Acta Obstet Gynecol Scand. 2014 Feb;93(2):132-7
pubmed: 24237585
Lancet Oncol. 2019 Sep;20(9):1211-1225
pubmed: 31371206
Ann Intern Med. 2017 Aug 15;167(4):268-274
pubmed: 28693043
Pediatr Blood Cancer. 2019 Jun;66(6):e27620
pubmed: 30815990
Eur J Cancer. 2017 May;77:31-39
pubmed: 28350996
Endocrinology. 2012 Jun;153(6):2551-5
pubmed: 22434084
BMJ. 2017 May 30;357:j2249
pubmed: 28559234
Am J Epidemiol. 1985 Jan;121(1):49-56
pubmed: 3155484
Br J Cancer. 2009 Aug 4;101(3):518-21
pubmed: 19603020
Scand J Public Health. 2011 Jul;39(7 Suppl):42-5
pubmed: 21775350
Nat Rev Cancer. 2004 Aug;4(8):617-29
pubmed: 15286741
Birth Defects Res A Clin Mol Teratol. 2004 Jan;70(1):13-9
pubmed: 14745890
Birth Defects Res A Clin Mol Teratol. 2014 Feb;100(2):79-91
pubmed: 24523198
Teratology. 2001 Nov;64(5):237-51
pubmed: 11745830
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):869-74
pubmed: 24367114
Genom Data. 2016 Aug 26;10:22-9
pubmed: 27630819
Cancer Epidemiol Biomarkers Prev. 2020 Jun;29(6):1081-1094
pubmed: 32482635
Cancer. 2005 Apr 1;103(7):1457-67
pubmed: 15712273
Acta Oncol. 1994;33(4):365-9
pubmed: 8018367
Eur J Cancer. 2009 May;45(7):1218-1231
pubmed: 19091545
Acta Oncol. 2018 Apr;57(4):440-455
pubmed: 29226751
Cancer Causes Control. 2021 Nov;32(11):1289-1298
pubmed: 34297242
Clin Epidemiol. 2015 Nov 17;7:449-90
pubmed: 26604824
PLoS One. 2017 Jul 27;12(7):e0181246
pubmed: 28749971
Am J Med Genet A. 2015 May;167A(5):1071-81
pubmed: 25711982
BMC Public Health. 2011 Jun 09;11:450
pubmed: 21658213
JNCI Cancer Spectr. 2020 Jun 11;4(5):pkaa052
pubmed: 33134832
Epigenetics. 2019 Feb;14(2):198-213
pubmed: 30870065
JAMA Oncol. 2019 Aug 01;5(8):1150-1158
pubmed: 31219523
Clin Epidemiol. 2021 Jul 19;13:533-554
pubmed: 34321928
Genet Epidemiol. 1995;12(5):467-74
pubmed: 8557179
Front Immunol. 2016 Jan 06;6:635
pubmed: 26779182