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.

Parental age and childhood cancer risk: A Danish population-based registry study

“…However, our results contradict the strong association between older paternal age (45+) and ALL that persisted with adjustment for maternal age in a recent registry-based Danish cohort study [10]. Our study includes more years of data thus we have more cases of ALL (1365 vs. 1110).…”

“…Although ethnic group is associated with childhood cancer risk [31], information on ethnic group is not collected in Danish national databases. As a proxy for ethnic group we assessed the inclusion of parental place of birth as a covariate in analyses and categorized it using the definitions of a previous Danish study (Danish/Western/non-Western) [10]. We left parental place of birth and parity in our final models as they changed estimates the most (>5% change).…”

“…Additionally, paternal age was not associated with most childhood cancer types after adjusting for maternal age [9]. A registry-based study in Denmark, including children born 1978–2010, examined paternal age (categorical/per 5-year increment) in relation to various cancer types and found an increased risk of ALL and decreased risk of CNS tumors with older parental age [10]. Specific cancer types have also been individually studied in relation to parental age with varying associations [11–20].…”

“…The purpose of this study was to assess the association between parental age and childhood cancer in a large population-based sample of children born in Denmark. Though a previous Danish study has examined paternal age, maternal age was not examined and our study includes more years thus it would expand on this previous study’s findings[10]. …”

Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years

“…Moreover, an accumulation of some sperm de novo point mutations and methylation alterations caused by APA, are specifically touching some genes related to neuropsychiatric disorders in offspring as Pex7 related to autism (Katz‐Jaffe et al, ), DRD4, RDMR_2, TBKBP1, TNXB, and DMPK related to schizophrenia and bipolar disorder as well as many others (Timothy et al, ). Regarding oncological transmission in the offspring, Urhoj et al () revealed a presence of association between APA and higher rate of childhood acute lymphoblastic leukemia with 13% of hazard rate each 5 years in APA. Indeed, non‐negligible autosomal dominant disorders are in increase due to selfish mutations tolerated at APA.…”