Background
Childhood cancer aetiology remains poorly understood, with genetics explaining only a small proportion of cases, suggesting a role for modifiable risk factors. Childhood cancers likely originate from influences acting before birth, and parental occupational exposures have therefore been investigated as potential contributors. Epidemiological evidence has been suggestive, with reported associations varying by cancer type and by the timing of exposure. For example, paternal exposures such as heavy metals and crystalline silica have been associated with childhood leukaemia, while other studies have reported null findings. This motivates large-scale studies with detailed occupational histories and consistent exposure assessment. 
 
Objectives
To investigate the associations between paternal occupational exposures (prior to conception) and childhood leukaemia, central nervous system (CNS) tumours, and lymphoma in the offspring. 
 
Methods
We conducted a nationwide, register-linked cohort study in Denmark using the data from DOCX-Generation (approx. 2.5 million recorded live births from 1977). Each child contributed one record and was followed from date of birth until the earliest of first cancer diagnosis, 19th birthday, date of emigration, date of death, or end of follow-up 31 December 2022. Outcomes were grouped a priori into leukaemia, CNS tumours, and lymphoma; only the first diagnosis up to age 19 years was considered. Paternal occupational exposures were assigned at the occupation level (ISCO-88) with general population job-exposure matrices (JEMs) for organic compounds, heavy metals, pesticides, and extremely low frequency magnetic fields (ELF-MF). Exposure before conception was evaluated. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (95% CI), adjusting for the pre-specified confounders including paternal age and family socioeconomic status. 
 
Results
Paternal occupational exposures assessed prior to conception were not associated with childhood leukaemia, CNS tumours, or lymphoma. 
 
Conclusions/Implications
Across the assessed agents, we observed no evidence that paternal occupational exposures before conception increased the risk of childhood leukaemia, CNS tumours, or lymphoma. These findings may indicate a weaker pre-conception pathway for the investigated outcomes and/or exposure misclassification from occupation-based exposure assignment that blunts detectable effects. To further evaluate paternal long-term exposure patterns, we are currently also investigating cumulative paternal exposure across multiple years before conception, to capture exposure duration and cumulative dose and to align exposure assessment with plausible biological windows for effects on male germ cells.