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Research

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4060 (Published 02 December 2020) Cite this as: BMJ 2020;371:m4060

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Major birth defects and cancer
  1. Dagrun Slettebø Daltveit, doctoral student1,
  2. Kari Klungsøyr, professor1 2,
  3. Anders Engeland, professor1 2,
  4. Anders Ekbom, professor3,
  5. Mika Gissler, professor4 5,
  6. Ingrid Glimelius, associate professor6 7,
  7. Tom Grotmol, senior consultant8,
  8. Laura Madanat-Harjuoja, adjunct professor9 10,
  9. Anne Gulbech Ording, clinical specialist11,
  10. Solbjørg Makalani Myrtveit Sæther, postdoctoral fellow12,
  11. Henrik Toft Sørensen, professor11,
  12. Rebecca Troisi, epidemiologist13,
  13. Tone Bjørge, professor1 8
  1. 1Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  2. 2Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway
  3. 3Unit of Clinical Epidemiology, Department of Medicine/Solna, Karolinska Institute, Stockholm, Sweden
  4. 4Information Services Department, Finnish Institute for Health and Welfare (THL), Helsinki, Finland
  5. 5Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
  6. 6Department of Medicine, Division of Clinical Epidemiology, Karolinska Institute, Stockholm, Sweden
  7. 7Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  8. 8Cancer Registry of Norway, Oslo, Norway
  9. 9Cancer Society of Finland, Finnish Cancer Registry, Helsinki, Finland.
  10. 10Department of Pediatrics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  11. 11Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
  12. 12Department of Health Promotion, Norwegian Institute of Public Health, Bergen, Norway
  13. 13Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
  1. Correspondence to: D S Daltveit dagrun.daltveit{at}uib.no (or @DagrunDaltveit on Twitter)
  • Accepted 4 October 2020

Abstract

Objective To examine associations between birth defects and cancer from birth into adulthood.

Design Population based nested case-control study.

Setting Nationwide health registries in Denmark, Finland, Norway, and Sweden.

Participants 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.

Main outcome measures Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.

Results Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.

Conclusions The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.

Footnotes

  • Contributors: TB, AE, and KK designed and planned the study. TB, IG, MG, and HTS obtained access to data. DSD did the data analysis and wrote the first draft of the manuscript with support from TB, AE, and KK. SMMS did preliminary analyses. All authors were involved in interpreting the results, revising the manuscript, and approving the final version. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. DSD is the guarantor.

  • Funding: This study was supported by the Norwegian Cancer Society (agreement No 5703714-2014). The research was designed, conducted, analysed, and interpreted by the authors independently of the funding sources.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Norwegian Cancer Society; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study was approved by ethics committees in Norway (2015/317/REK vest) and Stockholm, Sweden (2015/1642-31/2), and by the Data Protection Agency in Denmark (2015-57-0002). Permission to use health register data in Finland was granted by the Finnish Institute of Health and Welfare after consultation with the data protection authority (THL/68/5.05/2014 and THL/909/5.05/2015).

  • Data sharing: The datasets analysed during the current study are not freely available owing to national regulations, but similar data can be obtained from the register authorities.

  • The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

  • Dissemination to participants and related patient and public communities: The results of this study will be disseminated to relevant user organisations (Norwegian Cancer Society), patient groups, and healthcare workers.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

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