Psychiatric disorders among survivors of childhood acute lymphoblastic leukemia in Denmark and Sweden.

BACKGROUND: The diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) may impact mental health. We investigated the long-term risk of psychiatric disorders among survivors of ALL in a population-based cohort study. METHODS: We identified patients diagnosed with ALL in Denmark and Sweden before age 20 during 1982-2008. Survivors of ALL (n = 2026), their siblings (n = 3027), and population comparison subjects (n = 9713) were followed for hospital contacts for psychiatric disorders from 5 years after ALL diagnosis (or corresponding index date) until 2017. RESULTS: By age 30, the absolute risk of psychiatric hospital contacts was 19.9% (95% confidence interval [CI]: 17.9-22.1) for ALL survivors, 18.5% (95% CI: 16.9-20.2) for siblings, and 18.3% (95% CI: 17.3-19.2) for population comparison subjects. Overall, survivors were at higher risk of any psychiatric disorders than siblings (hazard ratio [HR] = 1.25; 95% CI: 1.04-1.50), and population comparison subjects (HR = 1.20; 95% CI: 1.06-1.35). The subgroup of survivors (n = 332) who received a hematopoietic stem cell transplantation (HSCT) and/or had a relapse were at highest risk of psychiatric disorders (HR = 2.07; 95% CI: 1.26-3.41 compared to siblings; HR = 1.67; 95% CI: 1.25-2.23 compared to population comparison subjects). CONCLUSIONS: The overall absolute risk of psychiatric hospital contacts among ALL survivors was close to that in siblings and population comparison subjects. The modestly increased relative risk was mainly driven by the subgroup of survivors who received HSCT and/or had a relapse. Our findings are reassuring for the large subgroup of ALL survivors without HSCT or relapse, and provide novel insight on both absolute and relative risk of hospital contacts for psychiatric disorders.

Surgical removal of tonsils and risk of COVID-19: a nested case-control study using data from UK Biobank and AMORIS Cohort.

BACKGROUND: To investigate the association between surgical removal of tonsils and risk of COVID-19 with different severity. METHODS: Through a nested case-control study during January 31st to December 31st 2020, including 58,888 participants of the UK Biobank, we investigated the association of tonsillectomy with the future risk of mild and severe COVID-19, using binomial logistic regression. We further examined the associations of such surgery with blood inflammatory, lipid and metabolic biomarkers to understand potential mechanisms. Finally, we replicated the analysis of severe COVID-19 in the Swedish AMORIS Cohort (n = 451,960). RESULTS: Tonsillectomy was associated with a lower risk of mild (odds ratio [95% confidence interval]: 0.80 [0.75-0.86]) and severe (0.87 [0.77-0.98]) COVID-19 in the UK Biobank. The associations did not differ substantially by sex, age, Townsend deprivation index, or polygenic risk score for critically ill COVID-19. Levels of blood inflammatory, lipid and metabolic biomarkers did, however, not differ greatly by history of surgical removal of tonsils. An inverse association between tonsillectomy and severe COVID-19 was also observed in the AMORIS Cohort, primarily among older individuals (> 70 years) and those with ≤ 12 years of education. CONCLUSIONS: Surgical removal of tonsils may be associated with a lower risk of COVID-19. This association is unlikely attributed to alterations in common blood inflammatory, lipid and metabolic biomarkers.

Mental illness and COVID-19 vaccination: a multinational investigation of observational & register-based data.

Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Using data from seven cohort studies (N = 325,298) included in the multinational COVIDMENT consortium, and the Swedish registers (N = 8,080,234), this study investigates the association between mental illness (defined using self-report measures, clinical diagnosis and prescription data) and COVID-19 vaccination uptake. Results from the COVIDMENT cohort studies were pooled using meta-analyses, the majority of which showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first and second dose of a COVID-19 vaccine among individuals with vs. without mental illness; the reduction was however greater among those not using psychiatric medication. Here we show that uptake of the COVID-19 vaccine is generally high among individuals both with and without mental illness, however the lower levels of vaccination uptake observed among subgroups of individuals with unmedicated mental illness warrants further attention.

Suicide Attempt and Suicide Death Among Spouses of Patients With Cancer.

Importance: Little is known about the risk of suicidal behavior in relation to having a spouse with a cancer diagnosis. Objective: To estimate the risk of suicide attempt and suicide death among spouses of patients with cancer. Design, Setting, and Participants: This nationwide cohort study in Denmark collected registry-based data from 1986 through 2016. Analyses were performed from August 8, 2022, to October 30, 2023. Individuals who had a spouse with a cancer diagnosed during 1986 to 2015 were compared with individuals whose spouse did not have a cancer diagnosis during the same period, randomly selected from the general population and matched by birth year and sex. Exposure: Having a spouse with a cancer diagnosis. Main Outcomes and Measures: Suicide attempt was identified through the Danish National Patient Register and the Danish Psychiatric Central Research Register, whereas suicide death was identified through the Danish Causes of Death Register, through 2016. Flexible parametric and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for suicide attempt and suicide death among spouses of patients with a cancer diagnosis. Results: The study included 409 338 exposed individuals and 2 046 682 unexposed individuals (median [IQR] age at cohort entry for both groups, 63 [54-70] years; 55.4% women). During the follow-up, 2714 incident cases of suicide attempt among exposed individuals (incidence rate [IR], 62.6 per 100 000 person-years) and 9994 among unexposed individuals (IR, 50.5 per 100 000 person-years) were identified, as well as 711 cases of suicide death among the exposed individuals (IR, 16.3 per 100 000 person-years) and 2270 among the unexposed individuals (IR, 11.4 per 100 000 person-years). An increased risk of suicide attempt (HR, 1.28; 95% CI, 1.23-1.34) and suicide death (HR, 1.47; 95% CI, 1.35-1.60) was observed among spouses of patients with cancer throughout the follow-up. The increased risk was particularly notable during the first year after the cancer diagnosis, with an HR of 1.45 (95% CI, 1.27-1.66) for suicide attempt and 2.56 (95% CI, 2.03-3.22) for suicide death. There was a greater risk increase for both suicide attempt and suicide death when the cancer was diagnosed at an advanced stage or when the spouse died after the cancer diagnosis. Conclusions and Relevance: These findings suggest a need for clinical and societal awareness to prevent suicidal behaviors among spouses of patients with cancer, particularly during the first year following the cancer diagnosis.

Leaving the parental home, cohabitation, and marriage after a hematologic malignancy in childhood-A register-based cohort study from the SALiCCS research program.

INTRODUCTION: Transitioning to adulthood often involves achieving independence from the parental home. We assessed whether the likelihood of leaving the parental home, cohabitation, and marriage was similar between patients who experienced a hematologic malignancy at a young age and their peers. METHODS: We identified 11,575 patients diagnosed with a hematologic malignancy under the age of 20 years between 1971 and 2011 in Denmark, Finland, and Sweden, 57,727 country-, age-, and sex-matched population comparisons and 11,803 sibling comparisons and obtained annual information on family and marital status by linking to the statistical institute databases. Hazard ratios (HR) for leaving the parental home, cohabitation and marriage were estimated using Cox proportional hazards modeling. RESULTS: Young adults with a history of a hematologic malignancy were slightly less likely to leave the parental home (HR 0.89; 95% confidence interval [CI] 0.86-0.92; HR 0.87 [95% CI 0.82-0.92]), cohabit with a nonmarital partner (HR 0.83 [95%CI 0.78-0.87]; HR 0.84 [95% CI 0.77-0.92]) and be married (HR 0.87 [95% CI 0.82-0.91]; HR 0.86 [95% CI 0.79-0.93]), compared with population comparisons and siblings, respectively. CONCLUSIONS: Our findings provide reassurance that young adults with a history of a hematologic malignancy show only a slight decrease in their likelihood of gaining independence from their childhood family and forming close interpersonal relationships compared to peers. While most patients are coping well in the long term, integrating structured psychosocial support into long-term follow-up is recommended to facilitate a timely and adequate transition into adulthood.

Early-Life Factors Associated With Adult-Onset Type 1 Diabetes: A Swedish Nationwide Cohort and Family-Based Study.

OBJECTIVE: Childhood-onset type 1 diabetes (T1D) is associated with perinatal factors, but data related to adult-onset T1D are scarce. This study aimed at investigating the association between early-life factors and adult-onset T1D in a Swedish nationwide cohort and family-based study. RESEARCH DESIGN AND METHODS: We included 1,813,415 individuals aged ≥18 years, born in Sweden 1983 to 2002, followed until 2020. T1D diagnosis (n = 3,283) was identified from the National Diabetes, Patient and Prescribed Drugs Registers, and perinatal exposures were obtained from the Medical Birth Register. We performed Cox proportional hazard (hazard ratio [95% CI]) regression with mutual adjustment for perinatal exposures, sex, birth year, and parental sociodemographic background and history of diabetes. We also compared T1D risks among siblings' groups identified from the Multiple Generation Register. RESULTS: The incidence rate of adult-onset T1D was 18.8 per 100,000 person-years. Year of birth (1.06 [1.01-1.10], per five additional years) and history of maternal (4.10 [3.09-5.43]) and paternal (6.24 [5.10-7.64]) T1D were associated with a higher incidence of adult-onset T1D, whereas female sex (0.69 [0.64-0.74]) and having parents born outside Sweden were associated with a lower incidence. Regarding perinatal exposures, only non-full-term birth (<39 weeks vs. ≥39 weeks) was associated with a higher incidence of adult-onset T1D (1.12 [1.04-1.22]). The sibling cohort results were consistent with the full cohort analysis. CONCLUSIONS: Perinatal factors seem to play a minor role in the development of adult-onset T1D compared with childhood-onset T1D, suggesting that triggers or accelerators of autoimmunity occurring later in life are more significant.

Fall-related injury among patients with vestibular schwannoma.

Vestibular schwannoma can cause vestibular dysfunction; however, conflicting evidence exists regarding whether this affects the incidence of fall-related injuries in this patient population. This matched cross-sectional and cohort study assess the risk of fall-related injuries in patients with vestibular schwannoma. The study included patients with vestibular schwannoma treated at a tertiary referral hospital in Sweden between 1988 and 2014. Information on fall-related injuries was obtained from the National Patient Register, and matched population comparisons were randomly selected in a 1:25 ratio. Fall-related injuries occurring pre- (within 5 years before the diagnosis of vestibular schwannoma) and post-diagnostically (up to 3 years after diagnosis or intervention) were registered. The association between vestibular schwannoma and fall-related injuries was estimated using logistic regression and Cox proportional hazards analyses. We identified 1153 patients with vestibular schwannoma (569 [49%] women and 584 [51%] men), and 28815 population comparisons. Among the patients, 9% and 7% had pre- and post-diagnostic fall-related injuries, respectively, and among the comparisons, 8% and 6% had pre- and post-diagnostic fall-related injuries, respectively. There was no increased risk of pre- (OR 1.14; CI 0.92-1.41) or post-diagnostic 1 year (HR 1.16; CI 0.87-1.54) or 3 years (HR 1.11; CI 0.89-1.29) fall-related injury among the total patient cohort. In age-stratified analyses, we found an increased risk of pre-diagnostic fall-related injury among patients aged 50-69 years (OR 1.42; CI 1.10-1.88). Patients who underwent middle fossa surgery, regardless of age, had an increased risk of post-surgery fall-related injury within 3 years of follow-up (HR 2.68; CI 1.06-6.81). We conclude that patients with vestibular schwannoma have a low risk of enduring fall-related injuries. Middle-aged patients with dizziness and fall-related injuries should be considered for a vestibular clinical evaluation. Our results highlight the importance of rehabilitation in avoiding future fall-related injuries among patients undergoing middle fossa surgery.

Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of 4 regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case analysis, and multiple imputation in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the United Kingdom. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with complete-case analysis or multiple imputation. We showed that RC methods resulted in more accurate estimation of the relationship between mobile phone use and health outcomes by combining self-reported data with objective operator-recorded data available for a subset of participants.

Effects of Recall and Selection Biases on Modeling Cancer Risk From Mobile Phone Use: Results From a Case-Control Simulation Study.

BACKGROUND: The largest case-control study (Interphone study) investigating glioma risk related to mobile phone use showed a J-shaped relationship with reduced relative risks for moderate use and a 40% increased relative risk among the 10% heaviest regular mobile phone users, using a categorical risk model based on deciles of lifetime duration of use among ever regular users. METHODS: We conducted Monte Carlo simulations examining whether the reported estimates are compatible with an assumption of no effect of mobile phone use on glioma risk when the various forms of biases present in the Interphone study are accounted for. Four scenarios of sources of error in self-reported mobile phone use were considered, along with selection bias. Input parameters used for simulations were those obtained from Interphone validation studies on reporting accuracy and from using a nonresponse questionnaire. RESULTS: We found that the scenario simultaneously modeling systematic and random reporting errors produced a J-shaped relationship perfectly compatible with the observed relationship from the main Interphone study with a simulated spurious increased relative risk among heaviest users (odds ratio = 1.91) compared with never regular users. The main determinant for producing this J shape was higher reporting error variance in cases compared with controls, as observed in the validation studies. Selection bias contributed to the reduced risks as well. CONCLUSIONS: Some uncertainty remains, but the evidence from the present simulation study shifts the overall assessment to making it less likely that heavy mobile phone use is causally related to an increased glioma risk.

Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study.

BACKGROUND: Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. METHODS: This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR). We excluded multiple births, deaths within the first month of life, individuals who could not be linked to MGR, or individuals with contradictory information on sex. Information on diagnoses of type 1 diabetes was retrieved by linkages to the National Diabetes Register and National Patient Register (1982-2020). Individuals with inconsistent records of diabetes type were excluded. We estimated the cumulative incidence and hazard ratios (HRs) of type 1 diabetes in adults (aged 19-30 years) and children (aged 0-18 years) by family history of type 1 diabetes and the heritability of adult-onset and childhood-onset type 1 diabetes based on tetrachoric correlations, using sibling pairs. FINDINGS: 2 943 832 individuals were born in Sweden during the study period, 2 832 755 individuals were included in the analysis of childhood-onset type 1 diabetes and 1 805 826 individuals were included in the analysis of adult-onset type 1 diabetes. 3240 cases of adult-onset type 1 diabetes (median onset age 23·4 years [IQR 21·1-26·2]; 1936 [59·7%] male and 1304 [40·2%] female) and 17 914 cases of childhood-onset type 1 diabetes (median onset age 9·8 years [6·2-13·3]; 9819 [54·8%] male and 8095 [45·2%] female) developed during follow-up. Having a first-degree relative with type 1 diabetes conferred an HR of 7·21 (95% CI 6·28-8·28) for adult-onset type 1 diabetes and 9·92 (9·38-10·50) for childhood-onset type 1 diabetes. The HR of developing type 1 diabetes before the age 30 years was smaller if a first-degree relative developed type 1 diabetes during adulthood (6·68 [6·04-7·39]) rather than during childhood (10·54 [9·92-11·19]). Similar findings were observed for type 1 diabetes in other relatives. Heritability was lower for adult-onset type 1 diabetes (0·56 [0·45-0·66]) than childhood-onset type 1 diabetes (0·81 [0·77-0·85]). INTERPRETATION: Adult-onset type 1 diabetes seems to have weaker familial aggregation and lower heritability than childhood-onset type 1 diabetes. This finding suggests a larger contribution of environmental factors to the development of type 1 diabetes in adults than in children and highlights the need to identify and intervene on such factors. FUNDING: Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Swedish Diabetes Foundation, and the China Scholarship Council.

Mobile phone use and brain tumour risk - COSMOS, a prospective cohort study.

BACKGROUND: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. METHODS: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007-2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. RESULTS: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98-1.02) for glioma, 1.01 (95 % CI 0.96-1.06) for meningioma, and 1.02 (95 % CI 0.99-1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62-1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62-1.52). CONCLUSIONS: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.

Early mortality in children with cancer in Denmark and Sweden: The role of social background in a setting with universal healthcare.

Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (ORadj_Low_vs_High 1.65 [95% CI 1.22-2.23]) and income (ORadj_Q1(lowest)_vs_Q4(highest) 1.77 [1.25-2.49]). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis.

Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom.

Headache is a common condition with a substantial burden of disease worldwide. Concerns have been raised over the potential impact of long-term mobile phone use on headache due to radiofrequency electromagnetic fields (RF-EMFs). We explored prospectively the association between mobile phone use at baseline (2009-2012) and headache at follow-up (2015-2018) by analysing pooled data consisting of the Dutch and UK cohorts of the Cohort Study of Mobile Phone Use and Health (COSMOS) (N = 78,437). Frequency of headache, migraine, and information on mobile phone use, including use of hands-free devices and frequency of texting, were self-reported. We collected objective operator data to obtain regression calibrated estimates of voice call duration. In the model mutually adjusted for call-time and text messaging, participants in the high category of call-time showed an adjusted odds ratio (OR) of 1.04 (95 % CI: 0.94-1.15), with no clear trend of reporting headache with increasing call-time. However, we found an increased risk of weekly headache (OR = 1.40, 95 % CI: 1.25-1.56) in the high category of text messaging, with a clear increase in reporting headache with increasing texting. Due to the negligible exposure to RF-EMFs from texting, our results suggest that mechanisms other than RF-EMFs are responsible for the increased risk of headache that we found among mobile phone users.

Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and Sweden.

BACKGROUND: The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer. METHODS AND FINDINGS: We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations. The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; p = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; p = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; p = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; p < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; p = 0.03), and there was no altered risk of parental death by suicide any time after the child's cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings. CONCLUSIONS: In this study, we observed an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child's cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.

Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

BACKGROUND: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation. METHODS: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay. CONCLUSIONS: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.

Risk of head and neck cancer in relation to blood inflammatory biomarkers in the Swedish AMORIS cohort.

Background: Inflammation is critically involved in the development of human cancer, and blood inflammatory biomarkers have been proposed to indicate the risk of different cancer types. Methods: Using the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) Cohort (N=812,073), we first performed a time-to-event analysis to evaluate the association of the baseline level of 12 blood inflammatory biomarkers measured during 1985-1996 with the subsequent risk of head and neck cancer (HNC) identified through the nationwide Swedish Cancer Register until end of 2020. A nested case-control study was further conducted to demonstrate the longitudinal trends of the studied biomarkers during the 30-year period prior to diagnosis of HNC. Results: In the time-to-event analysis, we identified a total of 2,510 newly diagnosed HNC cases. There was an increased risk of HNC per standard deviation (SD) increase of haptoglobin (hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 1.21-1.30), leukocytes (HR: 1.22; 95%CI: 1.17-1.28), sedimentation rate (HR: 1.17; 95%CI: 1.07-1.29), and monocytes (HR: 1.34; 95%CI: 1.07-1.68) at baseline, after adjustment for age, sex, fasting status, occupational status, and country of birth. In contrast, there was a decreased risk of HNC per SD increase of lymphocytes in % (HR: 0.85; 95%CI: 0.73-0.99) and lymphocyte-to-monocyte ratio (LMR) (HR: 0.81; 95%CI: 0.69-0.95) at baseline. In the nested case-control study using repeatedly measured biomarker levels, we found that individuals with HNC had consistently higher levels of haptoglobin, leukocytes, sedimentation rate, and monocytes, as well as consistently lower levels of lymphocytes in % and LMR, during the 30-year period prior to diagnosis, compared to controls. Conclusion: Based on a cohort of more than half a million participants with up to 35 years of follow-up, our findings provide solid evidence supporting the presence of alterations in blood inflammatory biomarkers during the decades before diagnosis of HNC.

Parental occupational exposure to metals and risk of cancer in the offspring: A register-based case-control study from Sweden.

BACKGROUND: Cancer risks in the offspring of mothers and fathers exposed to metals are unknown. We estimated the relative risks of childhood cancer, overall and by type, associated with parental occupational exposure to arsenic, cadmium, chromium, nickel, and lead. METHODS: We conducted a nested case-control study (1960-2015) of children born in Sweden aged 0-19 years diagnosed with cancer (National Cancer Register) matched 25:1 to controls on birth year and sex. We obtained parental occupational data around their birth from censuses and a nationwide register and identified exposure to each metal (yes/no, or higher/lower/no exposure) using the Swedish job-exposure matrix (SWEJEM). Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were estimated separately for maternal and paternal exposures using conditional logistic regression. RESULTS: We compared 9653 cases to 1,72,194 controls in maternal and 12,521 cases to 2,74,434 controls in paternal analyses, respectively. We found a 38% increased risk of cancer associated with maternal occupational exposure to arsenic (OR 1.38 [95% CI 1.06, 1.82]), likely driven by higher risks for lymphoma (OR 1.52 [0.73, 3.15]), central nervous system (CNS) (OR 1.49 [0.88, 2.54]) and other solid malignancies (OR 1.74 [1.14, 2.65]). There were also indications of higher risks of lymphoma in children of mothers exposed to nickel and iron, and of CNS tumours due to chromium exposure. No associations were observed from paternal occupational exposure to any of the metals. CONCLUSIONS: We found evidence of increased risks of cancer in children of mothers but not fathers occupationally exposed to arsenic and potentially other metals.

Neurocutaneous Syndromes, Perinatal Factors, and the Risk of Childhood Cancer in Sweden.

Importance: 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. Objective: 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. Exposures: 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. Main Outcomes and Measures: Childhood cancer risk (<20 years at diagnosis; identified from the National Cancer Register), including leukemia, lymphoma, and central nervous system (CNS) tumors. Results: 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. Conclusions and Relevance: 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.