Risk of Congenital Malformations in Children Born Before Paternal Cancer

BACKGROUND: Increased risk of congenital malformations in children fathered by men treated for cancer might be due to mutagenicity of cancer therapies. Finding of increased malformation prevalence in offspring born before paternal cancer would indicate a treatment-independent mechanism. METHODS: Through national registries, we obtained data on singletons born in Sweden from 1994 to 2014 (n = 1 796 160) and their fathers and mothers (1 092 950/1 092 011). Men with cancer (n = 23 932) fathered 26 601 and 9926 children before and after cancer diagnosis, respectively. Associations between paternal cancer, diagnoses retrieved from the Swedish Cancer Register, and offspring malformations, based on Swedish Medical Birth Register data, were estimated by logistic regression. RESULTS: Children conceived before paternal cancer had a statistically significantly increased risk of all malformations (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.02 to 1.15, P = .016, 3.8% vs 3.4%) and major malformations (OR = 1.09, 95% CI = 1.01 to 1.18, P = .03, 2.4% vs 2.1%). Eye and central nervous system cancers were associated with the highest risk of all malformations (OR = 1.30, 95% CI = 1.04 to 1.61, P = .02, 4.5% vs 3.4%). A similar trend was seen for testicular cancer. The malformation rates among children conceived before and after paternal cancer diagnosis were similar. CONCLUSIONS: The association between paternal cancer and risk of malformations in the offspring is not solely due to mutagenic effects of cancer therapy. The increase in prevalence of birth anomalies among children of fathers with malignancy might be due to cancer per se or a common underlying paternal factor, for example, genomic instability.