Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
PLoS Med. 2022 Feb 25;19(2):e1003903. doi: 10.1371/journal.pmed.1003903. eCollection 2022 Feb.
Birth defects have been consistently associated with elevated childhood cancer risks; however, the relationship between congenital heart disease (CHD) and childhood cancer remains conflicting. Considering the increasing patient population with CHD after improvements in their life expectancies, insights into this relationship are particularly compelling. Thus, we aimed to determine the relationship between CHD and cancer in Swedish children.
All individuals registered in the Swedish Medical Birth Register (MBR) between 1973 and 2014 were included in this population-based cohort study (n = 4,178,722). Individuals with CHD (n = 66,892) were identified from the MBR and National Patient Register, whereas cancer diagnoses were retrieved from the Swedish Cancer Register. The relationship between CHD and childhood cancer (<20 years at diagnosis) was evaluated using Cox proportional hazards regression models. We observed increased risks of cancer overall, leukemia, lymphoma, and hepatoblastoma in children with CHD, but after adjustment for Down syndrome, only the increased lymphoma (hazard ratio (HR) = 1.64, 95% confidence interval (CI) 1.11 to 2.44) and hepatoblastoma (HR = 3.94, 95% CI 1.83 to 8.47) risk remained. However, when restricting to CHD diagnoses from the MBR only, i.e., those diagnosed around birth, the risk for childhood cancer overall (HR = 1.45, 95% CI 1.23 to 1.71) and leukemia (HR = 1.41, 95% CI 1.08 to 1.84) was more pronounced, even after controlling for Down syndrome. Finally, a substantially elevated lymphoma risk (HR = 8.13, 95% CI 4.06 to 16.30) was observed in children with complex CHD. Limitations of the study include the National Patient Register not being nationwide until 1987, in addition to the rareness of the conditions under study providing limited power for analyses on the rarer cancer subtypes.
We found associations between CHD and childhood lymphomas and hepatoblastomas not explained by a diagnosis of Down syndrome. Stronger associations were observed in complex CHD.
出生缺陷与儿童癌症风险升高一直相关；然而，先天性心脏病 (CHD) 与儿童癌症之间的关系仍存在争议。考虑到随着 CHD 患者的预期寿命延长，患者人数不断增加，深入了解这种关系尤为重要。因此，我们旨在确定瑞典儿童中 CHD 与癌症之间的关系。
本基于人群的队列研究纳入了 1973 年至 2014 年期间在瑞典医疗出生登记处 (MBR) 注册的所有个体（n=4178722）。通过 MBR 和国家患者登记处确定 CHD 个体（n=66892），而癌症诊断则从瑞典癌症登记处获得。使用 Cox 比例风险回归模型评估 CHD 与儿童癌症（<20 岁诊断）之间的关系。我们观察到 CHD 儿童的总体癌症、白血病、淋巴瘤和肝母细胞瘤风险增加，但在调整唐氏综合征后，仅淋巴瘤（风险比 (HR)=1.64，95%置信区间 (CI) 1.11 至 2.44）和肝母细胞瘤（HR=3.94，95%CI 1.83 至 8.47）风险仍增加。然而，当仅限制在 MBR 中诊断的 CHD 时，即出生时左右诊断的 CHD，总体儿童癌症（HR=1.45，95%CI 1.23 至 1.71）和白血病（HR=1.41，95%CI 1.08 至 1.84）的风险更为明显，即使在控制唐氏综合征后也是如此。最后，在患有复杂 CHD 的儿童中观察到淋巴瘤风险显著升高（HR=8.13，95%CI 4.06 至 16.30）。本研究的局限性包括国家患者登记处直到 1987 年才覆盖全国，以及研究中罕见疾病的发病率限制了对罕见癌症亚型的分析能力。
我们发现 CHD 与儿童淋巴瘤和肝母细胞瘤之间存在关联，这些关联不能用唐氏综合征的诊断来解释。在复杂 CHD 中观察到更强的关联。
