Search

Background: Childhood cancer survivors (CCSs) face an increased risk of cardiovascular disease (CVD). This systematic review aims to provide the first synthesis of observational and interventional studies on the relationship between diet and cardiovascular health in CCSs., Methods: A comprehensive search was conducted for studies published between 1990 and July 2023 in PubMed, MEDLINE, CINAHL, Child Development & Adolescent Studies, and Cochrane Library. Eligible studies included observational and interventional studies examining the associations or effects of dietary factors on CVD incidence, cardiac dysfunction, or CVD risk factors in CCSs diagnosed before age 25 years., Results: Ten studies met the inclusion criteria (nine observational and one interventional). Collectively, they comprised 3485 CCSs (male, 1734; female, 1751). The outcomes examined across observational studies included characteristics of obesity, diabetes biomarkers, hypertension indicators, dyslipidaemia biomarkers, and metabolic syndrome. The evidence suggested that greater adherence to healthy diets was associated with lower body mass index, blood pressure, glucose, and triglycerides and higher high-density lipoprotein cholesterol. The 12-week lifestyle intervention study in childhood leukaemia survivors found no impact on obesity indicators., Conclusion: The review results indicate the potentially protective effects of healthy diets. However, the available research remains preliminary and limited, underscoring the need for more rigorous, adequately powered studies.

Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort., Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated., Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50., Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms., (© 2024. The Author(s).)

Background: Epidemiological studies often rely on self-reported health problems and validation greatly improves study quality. In a study of late effects after childhood cancer, we validated self-reported cardiovascular problems by contacting general practitioners (GPs). This paper describes: (a) the feasibility of this approach; and (b) the agreement between survivor-reports and reports from their GP., Methods: The Swiss Childhood Cancer Survivor Study (SCCSS) contacts all childhood cancer survivors registered in the Swiss Childhood Cancer Registry since 1976 who survived at least 5 years from cancer diagnosis. We validated answers of all survivors who reported a cardiovascular problem in the questionnaire. Reported cardiovascular problems were hypertension, arrhythmia, congestive heart failure, myocardial infarction, angina pectoris, stroke, thrombosis, and valvular problems. In the questionnaire, we further asked survivors to provide a valid address of their GP and a consent for contact. We sent case-report forms to survivors' GPs and requested information on cardiovascular diagnoses of their patients. To determine agreement between information reported by survivors and GPs, we calculated Cohen's kappa (κ) coefficients for each category of cardiovascular problems., Results: We used questionnaires from 2172 respondents of the SCCSS. Of 290 survivors (13% of 2172) who reported cardiovascular problems, 166 gave consent to contact their GP and provided a valid address. Of those, 135 GPs (81%) replied, and 128 returned the completed case-report form. Survivor-reports were confirmed by 54/128 GPs (42%). Of the 54 GPs, 36 (28% of 128) confirmed the problems as reported by the survivors; 11 (9% of 128) confirmed the reported problem(s) and gave additional information on more cardiovascular outcomes; and seven GPs (5% of 128) confirmed some, but not all cardiovascular problems. Agreement between GPs and survivors was good for stroke (κ = 0.79), moderate for hypertension (κ = 0.51), arrhythmias (κ = 0.41), valvular problems (κ = 0.41) and thrombosis (κ = 0.56), and poor for coronary heart disease (κ = 0.15) and heart failure (κ = 0.32)., Conclusions: Despite excellent GP compliance, it was found unfeasible to validate self-reported cardiovascular problems via GPs because they do not serve as gatekeepers in the Swiss health care system. It is thus necessary to develop other validation methods to improve the quality of patient-reported outcomes., (© 2024. The Author(s).)

Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors., Competing Interests: -AC Dietz is employed by and has equity in Shape Therapeutics, Inc. and was employed by and has equity in bluebird bio, Inc., neither of which provided financial support or oversight of this work.-AB received fees for lectures and/or boards from Astra-Zeneca, Novartis, Enanta paid to her institution as well as travel grants from Boehringer and Astra-Zeneca.-CEK received grants from the Swiss National Science Foundation-MO received research support from the Swiss Pediatric Oncology Society (SPOG)-DJW received grants/contracts from Vertex pharmaceuticals, Cystic Fibrosis Foundation Therapeutic Development Network, payment or honoraria for lectures/presentations by Cystic Fibrosis Foundation and American Board of Pediatrics-GS and RK received support for the present manuscript by Bernische Krebsliga and Lungenliga Bern-LSC received support from University of Alabama for COG Survivorship guidelines, royalties or licenses from Springer and Wolters Kluwer, payment or honoraria for lectures/presentations from the American Society for Hematology and the University of Miami, travel support from the First International Pediatric Cardio-oncology meeting, and participates on the Data Safety Monitoring Board or Advisory Board of the NCI PDQ-MG received a grant from the Swiss National Science Foundation, support for attending meetings and/or travel from the European Respiratory Society, has a leadership role in the BEAT-PCD ERS clinical research collaboration-NW received general research support from CANSEARCH Research Foundation, payment/honoraria and support to attend an international meeting from Swedish Orphan Biovitrum (SOBI), participates on a Data Safety Monitoring Board or Advisory Board from SOBI-PL received grants/contracts from Vertex and OM Pharma, payments or honoraria for lectures/presentations by Vertex, Vifor and OM Pharma, participates on a Data Safety Monitoring Board or Advisory Board from Polyphor, Santhera, Vertex, OM Pharma, Vifor, Sanofi Aventis-UH received a grant and support for attending meetings from the German Childhood Cancer Foundation,, (© 2024 Published by Elsevier Ltd.)

Background: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors., Methods: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m 2 ) and obesity (≥30 kg/m 2 ) using multinomial regression., Results: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts., Conclusions: Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This randomised controlled trial (RCT) assessed the effect of a 1-year, partially supervised, physical activity (PA) intervention on a cardiovascular disease (CVD) risk score in adult survivors of childhood cancer., Methods: We included childhood cancer survivors ≥16 y at enrolment, <16 y at diagnosis and ≥5 y in remission. The intervention group was asked to perform an additional ≥2.5 h of intense physical activity/week, controls continued exercise as usual; assessments were performed at baseline, 6 months (T6) and 12 months (T12). The primary endpoint was change in a CVD risk score (average z-score of waist circumference, blood pressure, fasting glucose, inverted high-density lipoprotein cholesterol, triglycerides, and inverted cardiorespiratory fitness) from baseline to T12. We performed intention-to-treat (ITT, primary) and 3 per protocol analyses., Results: We randomised 151 survivors (44% females, 30.4 ± 8.6 years). We found a significant and robust reduction of the CVD risk score in the intervention compared to the control group at T6 and T12 across all analyses; with a difference in the reduction of the CVD risk z-score of -0.18 (95% confidence interval -0.29 to -0.06, P = 0.003) at T12 in favour of the intervention group (ITT analysis)., Conclusions: This RCT showed that a long-term PA intervention can reduce CVD risk in long-term survivors of childhood cancer., Trial Registration: Clinicaltrials.gov: NCT02730767., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Meeting intervention requirements is crucial in behavioral trials. We examined patterns and predictors of physical activity (PA) adherence and contamination in a 1-year individualized randomized controlled PA behavioral intervention in childhood cancer survivors (CCS)., Methods: CCS aged ≥16 at enrolment, <16 at diagnosis, and ≥5 years in remission were identified from the Swiss Childhood Cancer Registry. We asked participants randomized to the intervention group to perform an additional ≥2.5 h of intense PA/week and controls to continue as usual. Adherence to the intervention was assessed by online diary (adherent if ≥2/3 of individual PA goal reached) and contamination for the control group by pre- and post-questionnaire including PA levels (contaminated if >60 min increase/week in PA). Predictors of adherence/contamination including quality of life (36-Item Short Form Survey) were assessed by questionnaire. We used logistic (control group) and mixed logistic regression models (exercise group) to estimate predictors of study adherence and contamination., Results: One hundred and forty-four survivors (30.4 ± 8.7 years old, 43% females) were included. Adherence was 48% (35/73) in the intervention group, while 17% (12/71) of controls contaminated group allocation. Predictors for PA adherence were female sex (OR 2.35, p = 0.03), higher physical (OR 1.34, p = 0.01) and mental quality of life (OR 1.37, p = 0.001), and week into the intervention (OR 0.98, p < 0.001). Clear differences in PA behavior of adherent and non-adherent participants were seen from week four. No significant predictors for contamination were found for controls., Conclusion: Adherence to PA behavior interventions remain challenging in both groups. Further long-term trials should consider intense motivational support within the first month, more detailed data collection for the control group, adjustments to power calculations and other study designs to minimize non-adherence and contamination., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks., Methods: The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence., Results: One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4-5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6-25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7-11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9-9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0-8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3-44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6-100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1-70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6-23.7)., Conclusions: Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early., (© 2022. The Author(s).)

Background: Research on germline genetic variants relies on enough eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits, participants can contribute genetic samples conveniently from their home. Demographic and clinical factors were identified previously that influenced participation in mailed self-collection. People with pre-existing heritable diagnoses might participate differently in germline DNA collection which might render sampling biased in this group. In this nationwide cross-sectional study, we analysed predictive factors of participation in DNA self-collection including heritable diagnoses., Methods: We identified childhood cancer survivors from the Swiss Childhood Cancer Registry for invitation to germline DNA self-sampling in September 2019. Participants received saliva sampling kits by postal mail at their home, were asked to fill them, sign an informed consent, and send them back by mail. Two reminders were sent to non-participants by mail. We compared demographic, clinical, and treatment information of participants with non-participants using univariable and multivariable logistic regression models., Results: We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 19-37), of which 463 (50%) participated. After the initial send out of the sampling kit, 291 (63%) had participated, while reminder letters led to 172 additional participants (37%). Foreign nationality (odds ratio [OR] 0.5; 95%-confidence interval [CI] 0.4-0.7), survivors aged 30-39 years at study versus other age groups (OR 0.5; CI 0.4-0.8), and survivors with a known cancer predisposition syndrome (OR 0.5; CI 0.3-1.0) were less likely to participate in germline DNA collection. Survivors with a second primary neoplasm (OR 1.9; CI 1.0-3.8) or those living in a French or Italian speaking region (OR 1.3; CI 1.0-1.8) tended to participate more., Conclusions: We showed that half of childhood cancer survivors participated in germline DNA self-sampling relying completely on mailing of sample kits. Written reminders increased the response by about one third. More targeted recruitment strategies may be advocated for people of foreign nationality, aged 30-39 years, and those with cancer predisposition syndromes. Perceptions of genetic research and potential barriers to participation of survivors need to be better understood., Trial Registration: Biobank: https://directory.bbmri-eric.eu/#/collection/bbmri-eric:ID:CH&#95;HopitauxUniversitairesGeneve:collection:CH&#95;BaHOP Research project : Clinicaltrials.gov: NCT04702321 ., (© 2021. The Author(s).)

Background: Chest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors., Methods: We investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey. We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors., Results: Forty-eight of 2382 (95%CI 2-3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16-20 years; OR 2.5, 95%CI 1.0-6.1), lymphoma (OR 3.8, 95%CI 1.2-11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0-30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0-4.2), surgery to the chest (OR 4.5, 95%CI 1.8-11.5), or chemotherapy (OR 2.9, 95%CI 1.0-8.1). The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors., Conclusion: It is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

Background: Cardiovascular disease is the leading nonmalignant cause of late deaths in childhood cancer survivors. Cardiovascular disease and cardiac dysfunction can remain asymptomatic for many years, but eventually lead to progressive disease with high morbidity and mortality. Early detection and intervention are therefore crucial to improve outcomes., Objective: In our study, we aim to assess the prevalence of preclinical cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography; determine the association between cardiac dysfunction and treatment-related risk factors (anthracyclines, alkylating agents, steroids, cardiac radiation) and modifiable cardiovascular risk factors (abdominal obesity, hypertension); investigate the development of cardiac dysfunction longitudinally in a defined cohort; study the association between cardiac dysfunction and other health outcomes like pulmonary disease, endocrine disease, renal disease, quality of life, fatigue, strength and endurance, and physical activity; and gain experience conducting a clinical study of childhood cancer survivors that will be extended to a national, multicenter study of cardiac complications., Methods: For this retrospective cohort study, we will invite ≥5-year childhood cancer survivors who were treated at the University Children's Hospital Bern, Switzerland with any chemotherapy or cardiac radiation since 1976 and who are ≥18 years of age at the time of the study for a cardiac assessment at the University Hospital Bern. This includes 544 childhood cancer survivors, of whom about half were treated with anthracyclines and/or cardiac radiation and half with any other chemotherapy. The standardized cardiac assessment includes a medical history focusing on signs of cardiovascular disease and its risk factors, a physical examination, anthropometry, vital parameters, the 1-minute sit-to-stand test, and echocardiography including 2-dimensional speckle tracking., Results: We will invite 544 eligible childhood cancer survivors (median age at the time of the study, 32.5 years; median length of time since diagnosis, 25.0 years) for a cardiac assessment. Of these survivors, 300 (55%) are at high risk, and 244 (45%) are at standard risk of cardiac dysfunction., Conclusions: This study will determine the prevalence of preclinical cardiac dysfunction in Swiss childhood cancer survivors, inform whether speckle tracking echocardiography is more sensitive to cardiac dysfunction than conventional echocardiography, and give a detailed picture of risk factors for cardiac dysfunction. The results will help improve primary treatment and follow-up care of children with cancer., Trial Registration: ClinicalTrials.gov NCT03790943; https://clinicaltrials.gov/ct2/show/NCT03790943., International Registered Report Identifier (irrid): DERR1-10.2196/17724., (©Christina Schindera, Claudia Elisabeth Kuehni, Mladen Pavlovic, Eva Simona Haegler-Laube, Daniel Rhyner, Nicolas Waespe, Jochen Roessler, Thomas Suter, Nicolas Xavier von der Weid. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.06.2020.)

Risk of cardiovascular disease (CVD), common in childhood cancer survivors (CCSs), may be affected by diet. We assessed sodium (Na) and potassium (K) intake, estimated from food frequency questionnaires (FFQs) and morning urine spots, and its associations with cardiovascular risk in CCSs. We stratified CCSs into three risk profiles based on (A) personal history (CVD, CVD risk factors, or CVD risk-free), (B) body mass index (obese, overweight, or normal/underweight), and (C) cardiotoxic treatment (anthracyclines and/or chest irradiation, or neither). We obtained an FFQ from 802 and sent a spot urine sample collection kit to 212, of which 111 (52%) returned. We estimated Na intake 2.9 g/day based on spot urine and 2.8 g/day based on FFQ; the estimated K intake was 1.6 g/day (spot urine) and 2.7 g/day (FFQ). CCSs with CVD risk factors had a slightly higher Na intake (3.3 g/day), than CCSs risk free (2.9 g/day) or with CVD (2.7 g/day, p = 0.017), and obese participants had higher Na intake (4.2 g/day) than normal/underweight CCSs (2.7 g/day, p < 0.001). Daily Na intake was above, and daily K intake below, the national recommended levels. Adult survivors of childhood cancer need dietary assistance to reduce Na and increase K intake., Competing Interests: The authors declare no conflict of interest.

Background: Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today's survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). Primary outcome of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. Secondary outcomes are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety)., Methods: A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant., Discussion: The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients., Trial Registration: Prospectively registered in clinicaltrials.gov [ NCT02730767 ], registration date: 10.12.2015.

Background: Previous studies on occupational exposures in parents and cancer risks in their children support a link between solvents and paints with childhood leukaemia. Few studies have focused specifically on benzene., Objectives: To examine whether parental occupational exposure to benzene is associated with an increased cancer risk in a census-based cohort of children., Methods: From a census-based cohort study in Switzerland, we included children aged <16years at national censuses (1990, 2000). We retrieved parental occupations reported at census and assessed exposure to benzene using a job exposure matrix. We identified incident cancer cases through record linkage with the Swiss Childhood Cancer Registry. We fitted Cox proportional-hazards models to assess associations between exposures and the following outcomes: any cancer, leukaemia, acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), lymphoma, non-Hodgkin lymphoma, central nervous system (CNS) tumours, and glioma. We adjusted models for a range of socio-economic, perinatal and environmental factors., Results: Analyses of maternal (paternal) exposure were based on 9.0 (13.2)millionperson years at risk and included 1004 (1520) cases of cancer, of which 285 (438) had leukaemia, 186 (281) lymphoma, 227 (339) a CNS tumour. Maternal exposure was associated with an increased risk of childhood leukaemia (hazard ratio 1.73, 95% CI 1.12-2.67) and ALL (1.88, 1.16-3.04). We found little evidence of an association for other outcomes or for paternal exposure. Adjusting for potential confounders did not materially affect the results., Conclusions: This nationwide cohort study suggests an increased risk of leukaemia among children whose mothers were exposed to benzene at work., (Copyright © 2017 Elsevier Ltd. All rights reserved.)