Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study

Abstract

Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0–19 years) and 218 980 matched population controls, born 1967–2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6–12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8–2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6–3.1) than males (OR = 2.1, 95% CI = 1.9–2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect–cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.

Cancer risk in the siblings of individuals with major birth defects: a large Nordic population-based case-control study

“…The cancer risk associated with having a sibling with birth defects in our study was lower than that of having one’s own birth defect observed in the same source population previously (children: OR = 1.1 versus 1.9, adults: OR = 1.0 versus 1.2). 3 , 6 Having any major birth defect of one’s own was associated with an increased risk of several specific cancers, 3 , 6 but having a sibling with any birth defect was only associated with an increased risk of lymphoid and haematopoietic malignancies (with similar effect estimates: own birth defect: OR = 1.2, 3 sibling with birth defects: OR = 1.16). For childhood cancer, we observed increased risk in three combinations of birth defects and cancers that were present for both own and sibling’s birth defects: (i) nervous system defects and any childhood cancer (own: OR = 6.1 3 , sibling’s: OR = 1.4); (ii) urinary system defects and germ cell tumours (own: OR = 3.9 3 , sibling’s: OR = 2.8); and (iii) limb defects and neuroblastoma (own: OR = 2.5, 3 sibling’s: OR = 2.0).…”

Etiology of Cancer in Children (Genetic and Non-Genetic Risk Factors)

“…Исследования воздействия пестицидов в жилых помещениях, как правило, основывались на самоотчетах, которые подвержены предвзятости отзывов, что может привести к завышению оценок риска. В некоторых недавних исследованиях использовалась близость жилых помещений к местам применения пестицидов [15]. Данный подход менее подвержен предвзятости, но все еще подвержен ошибкам измерений, которые могут ослабить оценки риска.…”

Risk Factors and Prevalence of Spina Bifida in Children Reported at Children Hospital (Lahore): A Mix Method Analysis

“…Spina bifida is a series of malfunctions of neural tube formation and human structure. This defect is more common in girls than boys by birth (Daltveit, 2023) This condition presents both in developed and developing countries as well as urban and rural areas (Aruleba & Jere, 2022). All congenital anomalies about neural tube closure which occur during the first three weeks of embryogenesis include neural tube defects, spina bifida, and anencephaly are severe forms of neural tube defects (Ten et al,2022).…”