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.

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.

Occurrence of mucosa-affecting diseases of the upper airways in middle ear cholesteatoma patients: a nationwide case-control study.

PURPOSE: Exploring a possible link between upper airway inflammation and the development of cholesteatoma by studying the association between mucosa-affecting diseases of the upper airways and cholesteatoma surgery. METHODS: This is a nationwide case-control study of 10,618 patients who underwent surgery for cholesteatoma in Sweden between 1987 and 2018. The cases were identified in the National Patient Register and 21,235 controls matched by age, sex and place of residency were included from national population registers. Odds ratios (OR) and corresponding 95% confidence intervals were used to assess the association between six types of mucosa-affecting diseases of the upper airways and cholesteatoma surgery. RESULTS: Chronic rhinitis, chronic sinusitis and nasal polyposis were more common in cholesteatoma patients than in controls (OR 1.5 to 2.5) as were both adenoid and tonsil surgery (OR > 4) where the strongest association was seen for adenoid surgery. No association was seen between allergic rhinitis and cholesteatoma. CONCLUSION: This study supports an association between mucosa-affecting diseases of the upper airways and cholesteatoma. Future studies should aim to investigate the mechanisms connecting mucosa-affecting diseases of the upper airways and cholesteatoma formation regarding genetic, anatomical, inflammatory and mucosa properties.

The relationship between congenital heart disease and cancer in Swedish children: A population-based cohort study.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Late mortality among survivors of childhood acute lymphoblastic leukemia diagnosed during 1971-2008 in Denmark, Finland, and Sweden: A population-based cohort study.

OBJECTIVE: Investigate all-cause and cause-specific late mortality after childhood acute lymphoblastic leukemia (ALL) in a population-based Nordic cohort. METHODS: From the cancer registries of Denmark, Finland, and Sweden, we identified 3765 five-year survivors of ALL, diagnosed before age 20 during 1971-2008. For each survivor, up to five matched comparison subjects were randomly selected from the general population (n = 18,323). Causes of death were classified as relapse related, health related, and external. Late mortality was evaluated by cumulative incidences of death from 5-year survival date. Mortality hazard ratios (HR) were evaluated with Cox proportional models. RESULTS: Among the survivors, 315 deaths occurred during a median follow-up of 16 years from 5-year survival date (range 0-42). The majority were attributable to relapse (n = 224), followed by second neoplasm (n = 45). Cumulative incidence of all-cause late mortality at 15 years from diagnosis decreased gradually over treatment decades, from 14.4% (95% confidence interval [CI]: 11.6-17.2) for survivors diagnosed during 1971-1981, to 2.5% (95% CI: 1.3-3.7) for those diagnosed during 2002-2008. This was mainly attributable to a reduction in relapse-related deaths decreasing from 13.4% (95% CI: 10.7-16.1) for survivors diagnosed during 1971-1981 to 1.9% (95% CI: 0.9-2.8) for those diagnosed during 2002-2008. Health-related late mortality was low and did not change substantially across treatment decades. Compared to comparison subjects, all-cause mortality HR was 40 (95% CI: 26-61) 5-9 years from diagnosis, and 4.4 (95% CI: 3.4-5.6) ≥10 years from diagnosis. CONCLUSIONS: Survivors of ALL have higher late mortality than population comparison subjects. Among the survivors, there was a temporal reduction in risk of death from relapse, without increments in health-related death.

Occupational exposure to pesticides in mothers and fathers and risk of cancer in the offspring: A register-based case-control study from Sweden (1960-2015).

Maternal and paternal occupational exposure to pesticides was linked to leukemia in the offspring in some previous studies. Risks for other cancers, particularly from maternal exposure, are largely unknown. We examined the association between maternal and paternal exposure to pesticides and childhood cancer in a Swedish register-based case-control study (1960-2015). Cancer cases <20 years old were identified from the Cancer Register (n = 17313) and matched to controls (1:25) on birth year and sex. Employment history of each biological parent around the child's birth was retrieved from six censuses and a nationwide register, and exposure to any of herbicides, insecticides, and fungicides was evaluated using the Swedish job-exposure matrix (SWEJEM) in 9653/172194 mothers and 12521/274434 fathers of cases/controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models for any cancer, leukemia, lymphoma, central nervous system [CNS], and other solid tumors. We found an OR of 1.42 (95% CI 0.78, 2.57; 12 exposed cases) for lymphoma and 1.30 (95% CI 0.88, 1.93; 27 exposed cases) for other solid tumors associated with maternal occupational exposure to pesticides. No associations were observed between maternal exposure and leukemia or CNS tumors, or paternal exposure and any of the cancers examined, except for a potential association between pesticides exposure and myeloid leukemia (OR 1.15 [95% CI 0.73, 1.79; 22 exposed cases]). Although these findings merit further investigation, they indicate that parental exposure to pesticides may lead to higher risks of childhood cancer even in settings of low exposure.

Number of siblings and survival from childhood leukaemia: a national register-based cohort study from Sweden.

BACKGROUND: Previous studies suggest worse leukaemia survival for children with siblings, but the evidence is sparse, inconsistent and does not consider clinical factors. We explored the associations between number of siblings in the household, birth order and survival from childhood acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML). METHODS: In this nationwide register-based study we included all children aged 1-14, diagnosed with ALL and AML between 1991-mid-2015 in Sweden (n = 1692). Using Cox regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) according to number of siblings and birth order, adjusting for known prognostic and sociodemographic factors. RESULTS: A tendency towards better ALL survival among children with one, or ≥2, siblings was observed, adjHRs (95% CI): 0.73 (0.49-1.10) and 0.63 (0.40-1.00), respectively. However, this was mainly limited to children with low risk profiles. An indication of better AML survival among children with siblings was seen, adjHRs (95% CI) 0.68 (0.36-1.29) and 0.71 (0.34-1.48) but diminished after adjusting for birth order. CONCLUSION: Our results do not support previous findings that a larger number of siblings is associated with poorer survival. Inconsistencies might be explained by underlying mechanisms that differ between settings, but chance cannot be ruled out.

Birth Characteristics Among Children Diagnosed with Neurofibromatosis Type 1 and Tuberous Sclerosis.

OBJECTIVE: To evaluate whether children with neurofibromatosis type 1 (NF1) and tuberous sclerosis have different birth characteristics compared with the general population. STUDY DESIGN: We identified all individuals born in Sweden between 1973 and 2014 from the nationwide Medical Birth Register for whom information on both biological parents was available (n = 4 242 122). Individuals with NF1 and individuals with tuberous sclerosis were identified using data from Swedish population-based health data registers. Using logistic regression models, we assessed the associations between these 2 neurocutaneous syndromes and birth characteristics in a cohort that included 1804 subjects with NF1 and 450 with tuberous sclerosis. RESULTS: Children with NF1 and tuberous sclerosis were significantly more likely to be born preterm and via cesarean delivery. In addition, children with NF1 were also more likely to be born with other birth characteristics, such as short length, a large head circumference, and a low Apgar score. Moreover, children with NF1 had an increased odds of being born with a high birth weight or large for gestational age (OR, 1.61; 95% CI, 1.42-1.82 and OR, 1.82; 95% CI, 1.60-2.06, respectively). CONCLUSION: Children with NF1 and tuberous sclerosis differ from the general population in terms of several birth characteristics, with the strongest associations observed for high birth weight and large for gestational age in individuals with NF1.

Surviving childhood cancer: a systematic review of studies on risk and determinants of adverse socioeconomic outcomes.

Substantial improvements in childhood cancer survival have resulted in a steadily increasing population of childhood cancer survivors. Whereas somatic late effects have been assessed in many studies, less is known about the impact of childhood cancer on socioeconomic outcomes in survivors. The aim of this article was to evaluate and summarise the evidence on the socioeconomic conditions of childhood cancer survivors and to identify survivors at particular risk of adverse socioeconomic outcomes. An extensive literature search of three electronic databases was conducted. Of 419 articles identified, 52 met the inclusion criteria. All the selected articles were appraised for quality, and findings were summarised in a narrative synthesis. Childhood cancer survivors were at higher risk of adverse socioeconomic outcomes with regard to educational achievement, income and social security benefits than the general population or a sibling comparison group. The risks for unemployment and a lower occupational position were significantly increased only for survivors of a central nervous system tumour. Notably, survivors of central nervous system tumours, survivors treated with cranial radiotherapy and those diagnosed at younger age independent of cancer type were determinants of particular adverse socioeconomic outcomes. Given the increasing population of childhood cancer survivors, targeted follow-up interventions and support strategies addressing not only the somatic and psychiatric late effects but also the socioeconomic difficulties that some childhood cancer survivors face is of high importance to reduce social inequity, and ensure a high quality of life after childhood cancer.

Suicides and deaths linked to risky health behavior in childhood cancer patients: A Nordic population-based register study.

BACKGROUND: Childhood cancer survivors have been reported to be vulnerable to psychiatric morbidities and risky health behavior. Suicides, substance abuse, accidents, and violence as causes of death can be regarded as an extreme manifestation of risky health behavior. In the current study, the authors studied the risk of suicide and other risky health behavior-related deaths among childhood cancer patients in Denmark, Finland, and Sweden. METHODS: Using linkage between national cancer, population, and cause-of-death registries, the authors investigated the causes of death in 29,285 patients diagnosed with cancer before age 20 years between 1971 and 2009 compared with a cohort of 146,282 age-matched, sex-matched, and country-matched population comparisons. Rate ratios (RRs) with 95% CIs were estimated using Poisson regression models, adjusting for demographic factors. RESULTS: The overall risk of dying of a risky health behavior was found to be increased among childhood cancer patients (RR, 1.25; 95% CI, 1.06-1.47) when compared with population comparisons. The elevated risk was statistically significant among patients with central nervous system tumors (RR, 1.49; 95% CI, 1.08-2.05) and patients diagnosed at ages 5 to 9 years and 15 to 19 years (RR, 1.50 [95% CI, 1.01-2.24] and RR, 1.31 [95% CI, 1.03-1.67], respectively). The overall risk of suicide was found to be increased (RR, 1.37; 95% CI, 1.02-1.83), and statistically significantly so when patients were diagnosed between ages 15 and 19 years (RR, 1.61; 95% CI, 1.09-2.39). CONCLUSIONS: Childhood cancer patients appear to have an increased risk of risky health behavior-related causes of death compared with the general population. The results of the current study suggest the importance of integrating psychosocial support into the follow-up care of these individuals.

Cancer patients hospitalised in the last week of life risk insufficient care quality - a population-based study from the Swedish Register of Palliative Care.

BACKGROUND: One-quarter of all cancer deaths in Sweden occur in hospitals. If the place of death affects the quality of end-of-life (EOL) is largely unknown. METHODS: This population-based, retrospective study included all adults cancer deaths reported to the Swedish Register of Palliative Care in 2011-2013 (N = 41,729). Hospital deaths were compared to deaths occurring in general or specialised palliative care, or in nursing homes with respect to care quality indicators in the last week of life. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with specialised palliative home care as reference. RESULTS: Preferred place of death was unknown for 63% of hospitalised patients and consistent with the actual place of death in 25% compared to 97% in palliative home care. Hospitalised patients were less likely to be informed when death was imminent (OR: 0.3; CI: 0.28-0.33) as were their families (OR: 0.51; CI: 0.46-0.57). Validated screening tools were less often used in hospitals for assessment of pain (OR: 0.32; CI: 0.30-0.34) or other symptoms (OR: 0.31; CI: 0.28-0.34) despite similar levels of EOL symptoms. Prescriptions of as needed drugs against anxiety (OR: 0.27; CI: 0.24-0.30), nausea (OR: 0.19; CI: 0.17-0.21), or pulmonary secretions (OR: 0.29; CI: 0.26-0.32) were less prevalent in hospitals. Bereavement support was offered after 57% of hospital deaths compared to 87-97% in palliative care units and 72% in nursing homes. CONCLUSIONS: Dying in hospital was associated with inferior end-of-life care quality among cancer patients in Sweden.

Socioeconomic differences in cancer survival among Swedish children.

BACKGROUND: Earlier evidence, also from high-income countries, suggests that parental socioeconomic status might influence survival from childhood cancer. This nationwide cohort study aimed to determine whether survival from childhood cancer in Sweden varies according to parental educational level and household income at the time of the child's diagnosis. METHODS: All children aged 1-14 years with a first primary diagnosis of cancer during 1991 to 2010 identified from the Swedish Cancer Register were included. Using Cox regression, the effects of parental educational level and household income on childhood cancer survival were estimated. RESULTS: For all diagnoses combined (n=4700), children of parents with compulsory or less education and upper-secondary education had poorer survival compared with children with parents who had the highest educational level, adjusted hazard ratios 1.28 (95% confidence interval 1.03-1.59) and 1.17 (1.00-1.38). Results for leukaemia and nervous system tumours showed a similar pattern but were not statistically significant in adjusted analyses. The observed differences began within the first year after diagnosis. Household income was not associated with survival. CONCLUSIONS: Also in Sweden, with universal health care, there are indications of inequalities in survival after childhood cancer diagnosis. Further studies are needed to determine which mechanisms explain the association.

The impact of waiting time on hearing outcome and patients' satisfaction after cholesteatoma surgery.

BACKGROUND: Cholesteatoma is a formation of epithelium mass in the middle ear. Surgery aims to prevent complications while maintain or improve hearing. AIMS/OBJECTIVES: To determine if waiting time until cholesteatoma surgery affects hearing outcome and patients' satisfaction. MATERIAL AND METHODS: A retrospective cohort study performed at the only Ear Nose Throat clinic in one county in Sweden. Sixty concomitant surgeries, both first time and revisions, were included. RESULTS: Of the 60 surgeries, 33 (55%) were performed within a 3-month period. The mean waiting time was 1.4 months. In the remaining 27 cases, the mean waiting time was 8.6 months. Both groups had preoperatively similar air conduction pure tone average (AC PTA4), 47.3 dB and 47.0 dB respectively. The mean AC PTA4 gain was greater in the group with waiting time ≤3 months (8.6 dB) compared to the >3 months group (1.2 dB, p = 0.040). The patients' satisfaction was lower in the latter group, but the difference was not statistically significant. CONCLUSIONS: This study indicates that longer waiting time to cholesteatoma surgery has a negative impact on postoperative hearing results but not on patients' satisfaction. SIGNIFICANCE: The outcome of this study suggests that waiting time to surgery can be a factor determining postoperative hearing results.

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.

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.

The Risk of Cholesteatoma in Individuals With First-degree Relatives Surgically Treated for the Disease.

Importance: Cholesteatoma in the middle ear is not regarded as a hereditary disease, but case reports of familial clustering exist in the literature, as well as observed familial cases in the clinical work. However, the knowledge regarding cholesteatoma as a hereditary disease is lacking in the literature. Objective: To assess the risk of cholesteatoma in individuals with a first-degree relative surgically treated for the same disease. Design, Setting, and Participants: In this nested case-control study in the Swedish population between 1987 and 2018 of first-time cholesteatoma surgery identified from the Swedish National Patient Register, 2 controls per case were randomly selected from the population register through incidence density sampling, and all first-degree relatives for cases and controls were identified. Data were received in April 2022, and analyses were conducted between April and September 2022. Exposure: Cholesteatoma surgery in a first-degree relative. Main Outcomes and Measures: The main outcome was first-time cholesteatoma surgery. The association between having a first-degree relative with cholesteatoma and the risk of cholesteatoma surgery in the index persons was estimated by odds ratios (ORs) and 95% CIs through conditional logistic regression analysis. Results: Between 1987 and 2018, 10 618 individuals with a first-time cholesteatoma surgery (mean [SD] age at surgery, 35.6 [21.5] years; 6302 [59.4%] men) were identified in the Swedish National Patient Register. The risk of having a cholesteatoma surgery was almost 4 times higher in individuals having a first-degree relative surgically treated for the disease (OR, 3.9; 95% CI, 3.1-4.8), but few cases were exposed overall. Among the 10 105 cases with at least 1 control included in the main analysis, 227 (2.2%) had at least 1 first-degree relative treated for cholesteatoma, while the corresponding numbers for controls were 118 of 19 553 control patients (0.6%). The association was stronger for individuals under the age of 20 years at first surgery (OR, 5.2; 95% CI, 3.6-7.6) and for a surgery involving the atticus and/or mastoid region (OR, 4.8; 95% CI, 3.4-6.2). There was no difference in the prevalence of having a partner with cholesteatoma between cases and controls (10 cases [0.3%] and 16 controls [0.3%]; OR, 0.92; 95% CI, 0.41-2.05), which implies that increased awareness does not explain the association. Conclusions and Relevance: In this Swedish case-control study using nationwide register data with high coverage and completeness, the findings suggest that the risk of cholesteatoma in the middle ear is strongly associated with a family history of the condition. Family history was nevertheless quite rare and can therefore only explain a limited number of all cases; these families could be an important source for information regarding the genetic background for cholesteatoma disease.

Income disparities between adult childhood cancer survivors and their peers-A register-based cohort study from the SALiCCS research programme.

BACKGROUND: Childhood cancer survivors face various adverse consequences. This Nordic register-based cohort study aimed to assess whether survivors of childhood cancer are more likely to have low income than their peers. METHODS: We identified 17,392 childhood cancer survivors diagnosed at ages 0 to 19 between 1971 and 2009 with 83,221 age-, sex-, and country-matched population comparisons. Annual disposable income at ages 20 to 50 years was retrieved from statistical offices (for 1990-2017) and categorized into low income and middle/high income. The number of transitions between income categories were assessed using binomial regression analyses. RESULTS: The prevalence of annual low income among childhood cancer survivors was 18.1% and 15.6% among population comparisons (risk ratio [RR] 1.17; 95% confidence interval [CI] 1.16-1.18). Compared to population comparisons, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to transition from low to middle/high income and 12% (10%-15%) more likely to transition from middle/high to low income during follow-up. Among those initially in the low income category, survivors were 7% (95% CI 3%-11%) more likely to remain in the low income category. If the initial category was middle/high income, childhood cancer survivors were 10% (95% CI 8%-11%) less likely to remain in the middle/high income and 45% (37%-53%) more likely to transition to the low income category permanently. CONCLUSIONS: Childhood cancer survivors are at higher risk for low income in adulthood than their peers. These disparities might be reduced by continued career counseling along with support in managing within the social security system.

Risk of Cancer in Children of Parents Occupationally Exposed to Hydrocarbon Solvents and Engine Exhaust Fumes: A Register-Based Nested Case-Control Study from Sweden (1960-2015).

BACKGROUND: It remains unclear whether parental occupational exposure to hydrocarbon solvents (HCS) or engine exhaust fumes (EEF) is associated with higher risks of cancer in the offspring. OBJECTIVES: Our aim was to estimate relative risks of childhood cancers associated with maternal or paternal exposure to aliphatic/alicyclic, aromatic, or chlorinated HCS or gasoline/diesel EEF. METHODS: We conducted a case-control study in which individuals <20y old, born 1960-2014, were identified from the Swedish National Cancer Register (1960-2015) at first cancer diagnosis and matched to population controls (1 case:25 controls) on birth year and sex. Maternal and paternal occupation around the child's birth was retrieved for 9,653 cases and 172,194 controls and 12,521 cases and 274,434 controls, respectively, using information from six censuses and a nationwide register. Using the Swedish job-exposure matrix (SWEJEM), we assessed exposure to HCS and EEF (any or higher/lower). Odds ratios (ORs) and 95% confidence intervals (CIs) of 15 childhood cancer subtypes were estimated using conditional logistic regression models adjusted for several confounders. RESULTS: Maternal exposure to aromatic HCS was associated with non-Hodgkin lymphoma (OR=1.64; 95% CI: 1.05, 2.58), aliphatic/alicyclic HCS with germ cell tumors (OR=1.52; 95% CI: 0.89, 2.59), and gasoline/diesel EEF with astrocytoma (OR=1.40; 95% CI: 1.04, 1.88), myeloid leukemia (OR=1.53; 95% CI: 0.84, 2.81), lymphomas (OR=1.60; 95% CI: 0.85, 3.02 for Hodgkin; OR=1.44; 95% CI: 0.71, 2.91 for non-Hodgkin), and epithelial tumors (OR=1.51; 95% CI: 0.93, 2.44). Paternal exposure to gasoline EEF was associated with Hodgkin lymphoma (OR=1.21; 95% CI: 1.01, 1.44) and soft tissue sarcomas (OR=1.22; 95% CI: 1.00, 1.48). No notable difference was observed between higher and lower exposure. DISCUSSION: Our findings suggest that occupational exposure to HCS or EEF, especially in the mother, may increase the risk of some childhood cancers. They add to the growing literature on adverse effects from HCS and EEF in the child, but replication of these associations in other populations is warranted. https://doi.org/10.1289/EHP11035.

Long-Term Risk of Hospitalization for Somatic Diseases Among Survivors of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) may be at increased long-term risk of hospitalization for somatic diseases. However, large population-based cohort studies with risk estimates for survivors successfully cured without experiencing a relapse or requiring hematopoietic stem cell transplantation (HSCT) are lacking. METHODS: Danish and Swedish patients diagnosed with ALL before age 20 years in 1982-2008 were identified in the national cancer registries. Five-year survivors and matched population comparisons without childhood cancer were followed for hospitalization for 120 somatic disease categories in the national hospital registries from 5 years postdiagnosis until 2017, and disease-specific hospitalization rate ratios (RR) were calculated. The mean cumulative count method was used to estimate the mean number of multiple and recurrent disease-specific hospitalizations per individual. RESULTS: A total of 2024 5-year survivors and 9797 population comparisons were included. The overall hospitalization rate was more than twice as high compared with comparisons (RR = 2.30, 95% confidence interval [CI] = 2.09 to 2.52). At 30 years postdiagnosis, the mean cumulative hospitalization count was 1.69 (95% CI = 1.47 to 1.90) per survivor and 0.80 (95% CI = 0.73 to 0.86) per comparison. In the subcohort without relapse or HSCT (n = 1709), the RR was 1.41 (95% CI = 1.27 to 1.58). CONCLUSIONS: Survivors of childhood ALL were at increased long-term risk for disease-specific hospitalizations; however, in survivors without relapse or HSCT, the rate was only modestly higher than in population comparisons without a childhood cancer. The absolute mean numbers of multiple and recurrent hospitalizations were generally low.

Employment status and occupational positions of childhood cancer survivors from Denmark, Finland and Sweden: A Nordic register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and late effects of treatment may affect survivors' possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings. METHODS: In a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards. FINDINGS: By 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (ORage30, 2.57; 95% CI, 2.35-2.81) and siblings (ORage30, 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age. INTERPRETATION: Survivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment. FUNDING: NordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3_175288].