title: Advanced paternal age and childhood cancer in offspring: A nationwide register-based cohort study.
abstract: Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood cancer in offspring in a large nationwide cohort of 1,904,363 children born in Denmark from 1978 through 2010. The children were identified in the Danish Medical Birth Registry and were linked to information from other national registers, including the Danish Cancer Registry. In total, 3,492 children were diagnosed with cancer before the age of 15 years. The adjusted hazard ratio of childhood cancer according to paternal age was estimated using Cox proportional hazards regressions. We found a 13% (95% confidence interval: 4-23%) higher hazard rate for every 5 years advantage in paternal age for acute lymphoblastic leukemia, while no clear association was found for acute myeloid leukemia (hazard ratio pr. 5 years = 1.02, 95% confidence interval: 0.80-1.30). The estimates for neoplasms in the central nervous system suggested a lower hazard rate with higher paternal age (hazard ratio pr. 5 years = 0.92, 95% confidence interval: 0.84-1.01). No clear associations were found for the remaining childhood cancer types. The findings suggest that paternal age is moderately associated with a higher rate of childhood acute lymphoblastic leukemia, but not acute myeloid leukemia, in offspring, while no firm conclusions could be made for other specific cancer types.
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, DK-1014 Copenhagen K, Denmark.
authors.forename: Stine Kjaer
authors.identifier: 0000-0002-2069-9723
authors.initials: SK
authors.lastname: Urhoj
authors.affiliation: Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen O, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Raaschou-Nielsen
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, DK-1014 Copenhagen K, Denmark.
authors.forename: Anne Vinkel
authors.initials: AV
authors.lastname: Hansen
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, DK-1014 Copenhagen K, Denmark.|Statistics Denmark, Sejrøgade 11, DK-2100 Copenhagen O, Denmark.
authors.forename: Laust Hvas
authors.initials: LH
authors.lastname: Mortensen
authors.affiliation: Section of Biostatistics, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, DK-1014 Copenhagen K, Denmark.
authors.forename: Per Kragh
authors.initials: PK
authors.lastname: Andersen
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Oster Farimagsgade 5, POB 2099, DK-1014 Copenhagen K, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Nybo Andersen
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003718:Denmark; D005190:Family; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology*; D010331:Paternal Age; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors
keywords: CNS neoplasms; acute lymphoblastic leukemia; acute myeloid leukemia; childhood cancer; paternal age