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Cancer risk in siblings of children with congenital malformations

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  • Yuelian Sun
  • Chun Sen Wu, Department of Endocrinology (P.L., S.L.A.), Aalborg University Hospital, DK-9000 Aalborg, Denmark; Department of Clinical Medicine (P.L.), Aalborg University, DK-9100 Aalborg, Denmark; Department of Clinical Biochemistry (S.L.A.), Aalborg University Hospital, DK-9000 Aalborg, Denmark; Department of Clinical Biochemistry (P.H.), Regionshospital Nordjylland, DK-9800 Hjørring, Denmark; Research Unit for Gynecology and Obstetrics (E.A.N.), Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense, Denmark; and Department of Clinical Epidemiology (J.O.), Aarhus University Hospital, DK-8200 Aarhus, Denmark.
  • ,
  • Onyebuchi A Arah, Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; UCLA Center for Health Policy Research, Los Angeles, CA, USA; California Center for Population Research, UCLA, Los Angeles, CA, USA.
  • ,
  • Jørn Olsen

PURPOSE: Cancer and birth defects cluster in families more often than expected by chance, but the reasons are neither well known nor well studied.

METHODS: From singletons born alive in Denmark between 1 January 1977 and 31 December 2007, we identified children who had no congenital malformations but had a full or half sibling with a congenital malformation (CM) diagnosed in the first year of life; this constituted the exposed group, while children whose siblings had no such condition constituted a reference group. We estimated cancer risks for children who had a full sibling or a half sibling with a CM using a Cox proportional hazards regression model. To control for confounding related to change of family structure, we estimated cancer risks for children from core families and children from broken families separately. Children were followed from birth up to 30 years of age (median follow-up 13.6 years). We obtained information on CMs and cancer from the Danish National Hospital Register and the Danish Cancer Registry.

RESULTS: We identified 991,454 (78%) children from core families with 53,995 children who had a full sibling with a CM and 277,773 (22%) children from broken families with 7200 children who had a full sibling with a CM and 6194 children who had a half sibling with a CM. Children who had a full sibling with a CM from both core and broken families showed, in general, no increased cancer risk compared with children whose siblings had no CM, except in the case of children who had a full sibling with a CM in the nervous system (HR=2.61, 95%CI:1.60-4.27) or in the eye, ear, face, or neck (HR=2.47, 95%CI: 1.46-4.18). Children who had a half sibling with a CM seemed to have a higher cancer risk in early adulthood (HR=1.87, 95%CI: 0.98-3.56).

CONCLUSIONS: Children who had a full sibling with a CM had no increased risk of cancer except for those who had a full sibling with a CM in the nervous system or in the eye, ear, face or neck. Children with a half-sibling with a CM tended to have an increased cancer risk in early adulthood, perhaps a result of chance. This study should be replicated using other data sources.

Original languageEnglish
JournalCancer epidemiology
Volume44
Pages (from-to)59-64
Number of pages6
ISSN1877-7821
DOIs
Publication statusPublished - Oct 2016

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  • Journal Article

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