Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
JAMA Netw Open. 2023 Jul 3;6(7):e2325482. doi: 10.1001/jamanetworkopen.2023.25482.
Neurocutaneous syndromes are associated with cancer predisposition and sometimes associated with perinatal factors. A better understanding of the association between neurocutaneous syndromes, perinatal factors, and childhood cancer is key for earlier cancer detection.
To evaluate the association of neurocutaneous syndromes and perinatal factors with childhood cancer risk in a cohort of Swedish children.
DESIGN, SETTING, AND PARTICIPANTS: In this nationwide cohort study, all children and adolescents up to age 20 years, from 1973 to 2015, were identified through the Swedish National Medical Birth Register (MBR), provided they had information on both biological parents. Analyses were conducted from April 2021 through May 2023.
Diagnoses of neurocutaneous syndromes were obtained from the MBR, National Patient Register, and Cause of Death register. Perinatal factors (birth weight, gestational age, birth weight by gestational age, 5-minute Apgar score, and head circumference) were obtained from the MBR.
Childhood cancer risk (<20 years at diagnosis; identified from the National Cancer Register), including leukemia, lymphoma, and central nervous system (CNS) tumors.
Among 4 173 108 included children (2 143 133 [51.4%] male, median [IQR] follow-up 20 [9.7-20] years), 1783 had neurofibromatosis type 1 (NF1), 444 tuberous sclerosis, 63 von Hippel-Lindau disease, and 39 ataxia-telangiectasia. An increased cancer risk was observed among children with any neurocutaneous syndrome (HR, 34.9; 95% CI, 30.8-39.6) and was particularly pronounced for CNS tumors (HR, 111.7; 95% CI, 96.8-128.8), except among children with ataxia-telangiectasia, where the increased risk was associated with lymphomas (HR, 233.1; 95% CI, 75.0-724.1). Leukemia risk was increased only among children with NF1 (HR, 4.1; 95% CI, 1.7-9.8). Several perinatal factors, including high birth weight, being born large for gestational age, preterm birth, low 5-minute Apgar score, and large head circumference had lesser associations with childhood cancer. Adjusting for neurocutaneous syndromes did not affect these associations.
In this nationwide cohort study, neurocutaneous syndromes were associated with an increased risk of childhood cancer, especially CNS tumors. Several perinatal factors had lesser associations with childhood cancer, independently of the presence of neurocutaneous syndromes. Other biological mechanisms likely underlie the association between perinatal factors and childhood cancer.
神经皮肤综合征与癌症易感性有关，有时与围产期因素有关。更好地了解神经皮肤综合征、围产期因素和儿童癌症之间的关联对于早期发现癌症至关重要。
在瑞典儿童队列中评估神经皮肤综合征和围产期因素与儿童癌症风险的关联。
设计、地点和参与者：在这项全国性队列研究中，通过瑞典国家医疗出生登记处（MBR）识别了所有年龄在 20 岁以下的儿童和青少年，前提是他们有父母双方的信息。分析于 2021 年 4 月至 2023 年 5 月进行。
神经皮肤综合征的诊断来自 MBR、国家患者登记处和死因登记处。围产期因素（出生体重、胎龄、出生体重与胎龄比、5 分钟阿普加评分和头围）来自 MBR。
儿童癌症风险（<20 岁时诊断；从国家癌症登记处获得），包括白血病、淋巴瘤和中枢神经系统（CNS）肿瘤。
在 4173108 名纳入的儿童中（2143133 名男性[51.4%]，中位数[IQR]随访 20 [9.7-20]年），1783 名患有神经纤维瘤病 1 型（NF1）、444 名患有结节性硬化症、63 名患有 von Hippel-Lindau 病和 39 名患有共济失调毛细血管扩张症。患有任何神经皮肤综合征的儿童癌症风险增加（HR，34.9；95%CI，30.8-39.6），特别是中枢神经系统肿瘤（HR，111.7；95%CI，96.8-128.8），除了患有共济失调毛细血管扩张症的儿童，其风险增加与淋巴瘤有关（HR，233.1；95%CI，75.0-724.1）。白血病风险仅在 NF1 儿童中增加（HR，4.1；95%CI，1.7-9.8）。一些围产期因素，包括高出生体重、出生时大于胎龄、早产、低 5 分钟阿普加评分和大头围，与儿童癌症的相关性较低。调整神经皮肤综合征后，这些关联并未受到影响。
在这项全国性队列研究中，神经皮肤综合征与儿童癌症风险增加有关，尤其是中枢神经系统肿瘤。一些围产期因素与儿童癌症的相关性较低，独立于神经皮肤综合征的存在。其他生物学机制可能是围产期因素与儿童癌症之间关联的基础。
