Risk of Birth Abnormalities in the Offspring of Men With a History of Cancer: A Cohort Study Using Danish and Swedish National Registries

Abstract

BackgroundThe potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring.MethodsWe identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1 777 765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1 769 0795 children without a paternal history of cancer, 25 926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided.ResultsThe offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, Pinteraction = .84).ConclusionWe observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.

Mortality among offspring of women diagnosed with cancer: A population‐based cohort study

“…14 Most studies report no chromosomal abnormalities, [20][21][22][23][24] malformations, 21,24-28 congenital defects 21 or cancer 29,30 in offspring of cancer survivors, with the exceptions of Dalberg et al 15 who noted an increased risk of malformation among women who conceived after treatment for breast cancer, Winther et al 28 who noted a small (not significantly increased) risk of malformations in children with a parent who received irradiation for childhood cancer and Stahl et al 27 who observed statistically significant but modestly increased risk of major congenital abnormalities among offspring of males with a history of cancer. In accordance with these previous publications, we observed an increased mortality risk in offspring of survivors of hematological cancer, a substantial part of whom will have received radiation therapy for (non) Hodgkin lymphoma.…”

Genetic Disease in the Children of Danish Survivors of Childhood and Adolescent Cancer

“…13,15,23,45,49 However, conflicting results have recently been published on the risk of malformations in offspring of male survivors. [51][52][53][54] Congenital malformations, stillbirths, and neonatal deaths, taken together, might be associated with high-dose uterine …”

Current options for preservation of fertility in the male

“…Another more recent United States cohort study also showed no increased risk of malformations or premature birth in the offspring of male cancer survivors (18). However, the largest cohort study to date with greater power than previous studies examined all singleton births in Denmark and Sweden between 1994 and 2004 and showed a 17% increased risk of major congenital abnormalities in the offspring of male cancer survivors (19). This risk was independent of whether natural conception or assisted reproductive technology was employed (19).…”

“…However, the largest cohort study to date with greater power than previous studies examined all singleton births in Denmark and Sweden between 1994 and 2004 and showed a 17% increased risk of major congenital abnormalities in the offspring of male cancer survivors (19). This risk was independent of whether natural conception or assisted reproductive technology was employed (19). Whether this increased risk can be attributed to the effects of cancer treatment, a systemic genetic instability leading to both the development of cancer and conception of a child with a birth defect, or an effect of the cancer itself on the integrity of sperm DNA remains to be fully investigated.…”