Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study

BackgroundIn recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991–2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findingsWe conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991–2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34–1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29–1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15–1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14–1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96–10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48–0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51–0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.ConclusionsOur findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Edda Bjork Thordardottir and co-workers study health outcomes among migrants from the former Yugoslavia to Sweden.     

Patient education-level affects treatment allocation and prognosis in esophageal- and gastroesophageal junctional cancer in Sweden

BackgroundLow socioeconomic status and poor education elevate the risk of developing esophageal- and junctional cancer. High education level also increases survival after curative surgery. The present study aimed to investigate associations, if any, between patient education-level and treatment allocation after diagnosis of esophageal- and junctional cancer and its subsequent impact on survival.MethodsA nation-wide cohort study was undertaken. Data from a Swedish national quality register for esophageal cancer (NREV) was linked to the National Cancer Register, National Patient Register, Prescribed Drug Register, Cause of Death Register and educational data from Statistics Sweden. The effect of education level (low; ≤9 years, intermediate; 10–12 years and high >12 years) on the probability of allocation to curative treatment was analyzed with logistic regression. The Kaplan-Meier-method and Cox proportional hazard models were used to assess the effect of education on survival.ResultsA total of 4112 patients were included. In a multivariate logistic regression model, high education level was associated with greater probability of allocation to curative treatment (adjusted OR: 1.48, 95% CI: 1.08–2.03, p = 0,014) as was adherence to a multidisciplinary treatment-conference (adjusted OR: 3.13, 95% CI: 2.40–4.08, p < 0,001). High education level was associated with improved survival in the patients allocated to curative treatment (HR: 0.82, 95% CI: 0.69–0.99, p = 0,036).DiscussionIn this nation-wide cohort of esophageal- and junctional cancer patients, including data regarding many confounders, high education level was associated with greater probability of being offered curative treatment and improved survival.     

Birthweight and risk of thyroid cancer and its histological types: A large cohort study

BackgroundThe aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk.ObjectiveTo investigate if birthweight is associated with the later risk of thyroid cancer and its histological types.Methods246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936–1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI).ResultsDuring follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03–1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07–2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90–1.59] per kilogram).ConclusionA heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.     

Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study

BackgroundA knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID.Methods and findingsWe conducted a population-based cohort study of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. All individuals were followed from birth until cancer diagnosis, emigration, death, or 31 December 2016 (up to age 43 years), whichever came first. Incident cancers were identified from the Swedish Cancer Register. We fitted Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of cancer risk in relation to ID after adjusting for several potential confounders. We analyzed ID by severity, as well as idiopathic ID and syndromic ID separately. We performed a sibling comparison to investigate familial confounding. The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID. Compared with the reference group (individuals without ID and without a full sibling with ID), individuals with ID were in general more likely to be male. The median follow-up time was 8.9 and 23.0 years for individuals with ID and individuals without ID, respectively. A total of 188 cancer cases were identified among individuals with ID (incidence rate [IR], 62 per 1,000 person-years), and 24,960 among individuals in the reference group (IR, 31 per 1,000 person-years). A statistically significantly increased risk was observed for any cancer (HR 1.57, 95% CI 1.35–1.82; P < 0.001), as well as for several cancer types, including cancers of the esophagus (HR 28.4, 95% CI 6.2–130.6; P < 0.001), stomach (HR 6.1, 95% CI 1.5–24.9; P = 0.013), small intestine (HR 12.0, 95% CI 2.9–50.1; P < 0.001), colon (HR 2.0, 95% CI 1.0–4.1; P = 0.045), pancreas (HR 6.0, 95% CI 1.5–24.8; P = 0.013), uterus (HR 11.7, 95% CI 1.5–90.7; P = 0.019), kidney (HR 4.4, 95% CI 2.0–9.8; P < 0.001), central nervous system (HR 2.7, 95% CI 2.0–3.7; P < 0.001), and other or unspecified sites (HR 4.8, 95% CI 1.8–12.9; P = 0.002), as well as acute lymphoid leukemia (HR 2.4, 95% CI 1.3–4.4; P = 0.003) and acute myeloid leukemia (HR 3.0, 95% CI 1.4–6.4; P = 0.004). Cancer risk was not modified by ID severity or sex but was higher for syndromic ID. The sibling comparison showed little support for familial confounding. The main study limitations were the limited statistical power for the analyses of specific cancer types, and the potential for underestimation of the studied associations (e.g., due to potential underdetection or delayed diagnosis of cancer among individuals with ID).ConclusionsIn this study, we found that individuals with ID showed an increased risk of any cancer, as well as of several specific cancer types. These findings suggest that extended surveillance and early intervention for cancer among individuals with ID are warranted.

In a nationwide cohort study in Sweden, Qianwei Liu and co-workers report on cancer risk in people with intellectual disability.     

Maternal pregestational diabetes and risk of acute lymphoblastic leukemia in the offspring: A population-based study in Northern Italy

IntroductionThis population-based study aims to evaluate the association between maternal pregestational diabetes and risk of acute lymphoblastic leukemia (ALL) in the offspring.MethodsAll 241,958 children born in three Northern Italy provinces 1998–2010 were followed from birth until first cancer diagnosis (National Childhood Cancer Register), age 15 years, or 31 December 2017. We computed hazard ratio (HR) and 95% CI of ALL in relation to the presence of maternal diabetes through Cox proportional regression models.ResultsWe observed 145 cases of ALL, with a higher incidence in children born to women with pregestational diabetes compared to the others (12.4 vs 4.6). Adjusted hazard ratio of ALL was 2.6 (CI, 0.6–10.5) for maternal diabetes.DiscussionWe estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.     

Parental Socioeconomic Status,Childhood Asthma and Medication Use – A Population-Based Study

Background

Little is known about how parental socioeconomic status affects offspring asthma risk in the general population, or its relation to healthcare and medication use among diagnosed children.

Methods

This register-based cohort study included 211,520 children born between April 2006 and December 2008 followed until December 2010. Asthma diagnoses were retrieved from the National Patient Register, and dispensed asthma medications from the Prescribed Drug Register. Parental socioeconomic status (income and education) were retrieved from Statistics Sweden. The associations between parental socioeconomic status and outcomes were estimated by Cox proportional hazard regression.

Results

Compared to the highest parental income level, children exposed to all other levels had increased risk of asthma during their first year of life (e.g. hazard ratio, HR 1.19, 95% confidence interval, CI 1.09–1.31 for diagnosis and HR 1.17, 95% CI 1.08–1.26 for medications for the lowest quintile) and the risk was decreased after the first year, especially among children from the lowest parental income quintile (HR 0.84, 95% CI 0.77–0.92 for diagnosis, and HR 0.80, 95% CI 0.74–0.86 for medications). Further, compared to children with college-educated parents, those whose parents had lower education had increased risk of childhood asthma regardless of age. Children with the lowest parental education had increased risk of an inpatient (HR 2.07, 95% CI 1.61–2.65) and outpatient (HR 1.32, 95% CI 1.18–1.47) asthma diagnosis. Among diagnosed children, those from families with lower education used fewer controller medications than those whose parents were college graduates.

Conclusions

Our findings indicate an age-varying association between parental income and childhood asthma and consistent inverse association regardless of age between parental education and asthma incidence, dispensed controller medications and inpatient care which should be further investigated and remedied.     

Maternal smoking during pregnancy and the risk of childhood brain tumors: Results from a Swedish cohort study

BackgroundTobacco metabolites and carcinogens can be found in placental and umbilical cord tissues of fetuses exposed to maternal smoking. However, studies regarding maternal smoking during pregnancy and childhood brain tumor (CBT) have shown inconsistent results.MethodsAll children born in Sweden between 1983 and 2010 and with information about maternal smoking during pregnancy, obtained from the Swedish Medical Birth Register, were included in this population based cohort study (n = 2,577,305). CBT cases were identified from the National Cancer Register. Cox regression models were used to estimate the effect of maternal smoking during pregnancy on the risk of CBTs.ResultsWe identified 1039 cases of CBT in the cohort. Overall, there was little or no effect of maternal smoking during pregnancy on the risk of CBTs. However, in analyses stratified by age at diagnosis and child’s sex, positive associations were found among 5–9 years old children. In this age interval, maternal smoking during pregnancy was associated with an increased risk of all CBTs combined only among male children (RR = 1.50, 95% CI 0.96–2.34), while for astrocytoma there was a positive association in both male (RR = 2.00, 95% CI 1.02–3.91) and female children (RR = 1.80, 95% CI 0.85–3.82).ConclusionResults from this large Swedish cohort study suggest that even though maternal smoking during pregnancy has a limited overall effect on CBTs, it may increase the risk of astrocytomas.     

Childhood Household Dysfunction,Social Inequality and Alcohol Related Illness in Young Adulthood. A Swedish National Cohort Study

The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973–82 (n = 872 912), which was followed from age 18 to 29–40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7–2.5], two CHD indicators 5.6 [4.4–7.1], three or more indicators 9.4 [7.1–12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks–those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9–14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4–1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage.     

Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study

BackgroundCirculating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.Methods and findingsThe derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3–5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses.Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799–2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491–1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527–1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362–1.775), renin HR 1.501 (95% CI 1.305–1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297–1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307–1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243–1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131–1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226–1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255–1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316–1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134–1.396), spondin-1 HR 1.295 (95% CI 1.156–1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237–1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129–1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307–1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490–2.056).The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.ConclusionsProfiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00799903","term_id":"NCT00799903"}}NCT00799903.

Niclas Eriksson and colleagues report associations between 157 cardiovascular plasma biomarkers and cardiovascular death in patients.     

Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis

ObjectiveRecently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor.MethodsEligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients’ ethnicities, tumor types, detection methods, and analysis types.ResultsData from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51–2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02–4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67–2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09–2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62–5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28–4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg’s test, p = 0.325; Egger’s test, p = 0.441).ConclusionIn this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type.     

Prediction of Poor Prognosis in Breast Cancer Patients Based on MicroRNA-21 Expression: A Meta-Analysis

BackgroundMicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer.MethodsThe meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI).ResultsOur meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics.ConclusionOur results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians.     

Colorectal cancer among farmers in the AGRICAN cohort study

ObjectivesSpecific farming types and tasks have rarely been studied in relation to colorectal cancer (CRC). We evaluated associations between 5 types of livestock and 13 types of crops in relation to CRC and its subsites within the Agriculture and Cancer (AGRICAN) study.MethodsAGRICAN cohort includes 181,842 agricultural workers living in 11 French geographical areas. Data on farming types and tasks was collected by self-administered questionnaires. We identified 2 609 CRC, 972 right colon, 689 left colon and 898 rectal incident cancer cases during follow-up from 2005 to 2015. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).ResultsSignificantly increased CRC risk was observed for farmers producing horses (HR=1.18, 95% CI 1.06–1.31), sunflower (HR=1.23, 95% CI 1.03–1.45) and field vegetables (HR=1.18, 95% CI 1.02–1.36). Positive associations were also observed for pig, poultry and wheat/barley. Some associations were observed only for specific subsites: left colon cancer was associated with fruit growing (HR=1.36, 95% CI 1.09–1.70) and potato (HR=1.28, 95% CI 1.05–1.57). Tasks related to livestock (animal care, insecticide treatment, disinfection of milking equipment and building) or to crop (haymaking, sowing, pesticide treatment, seed treatment, harvesting) were also associated with CRC. Duration and size of farming types/task increased the risk for some of the associations. Analysis stratified by sex suggested an interaction with several farming types/task.ConclusionsThe current study showed original and positive findings for several farming types and tasks and CRC risk, overall and by subsites.     

Childhood cancer in Aden,Yemen

BackgroundCancer in children is increasingly recognized as a major and growing health problem in different developed and developing countries. In Yemen, it is still difficult to know the extent of cancer and its determinants among children. This study was conducted to determine the magnitude of childhood cancer in Aden and provide the preliminary baseline data by age and sex.MethodsBasic epidemiologic data was retrieved from all paediatric cancer <15 years age registered in Aden Caner Registry (ACR), Yemen, from 1997 to 2006.ResultsThe results showed a total of 483 childhood cancers <15 years age comprising12.7% of all registered malignancies with a male to female ratio of 1.5:1. The predominant age affected was 5–9 years in (38.3%) children. The most frequent cancer among Yemeni children was leukaemia 160 (33.1%) followed by lymphoma 152 (31.5%), CNS tumors 35 (7.2%) and bone tumours 25 (5.2%). An interesting and unusual finding was the frequency of acute myeloid leukaemia twice more common in female (66.7%) than male (33.3%). Lymphoma was the most common cancer in children >5 years. An interesting comparison was the preponderance of non-Hodgkins's lymphoma over Hodgkin's disease (1.6:1) stronger in female (3:1) than male (1.25:1). Medulloblastoma was the most common CNS tumour followed by astrocytoma, an infrequent finding in childhood cancer. Osteosarcoma was the most frequent bone tumour (male:female ratio of 1.8:1). A female preponderance was noticed in chondrosarcoma that was not yet documented. The blastoma group was common in younger age group. Retinoblastoma and nephroblastoma predominated in female while neuroblastoma, hepatoblastoma and soft tissue sarcomas in male.ConclusionIt is concluded that there is a lower frequency of childhood cancer in Aden when compared with developed countries. It may explained by the fact that a large number of childhood cancers remain undiagnosed due to limitations of diagnostic facilities or under registration. Central paediatric hospitals should be provided with essential diagnostic and therapeutic services that should be freely available to all children with cancer.     

Male-origin microchimerism and endometrial cancer: A prospective case-cohort study

BackgroundMany women carry male cells of presumed fetal origin–so-called male-origin microchimerism (MOM)–in their circulation and tissues. Studies have found reduced risks of hormone dependent cancers, including breast and ovarian cancer, among MOM-positive women. The aim of this study was to investigate the association between MOM and endometrial cancer.MethodsWe designed a prospective case-cohort study including 76 cases and 505 controls from the Diet, Cancer and Health cohort aged 50–64 years and cancer-free at enrolment in 1993–1997. We analyzed blood samples for the presence of Y-chromosome (DYS14). We examined the association between MOM and endometrial cancer in weighted Cox regression models. As a negative control outcome, we studied the association between MOM and injuries to test for spurious associations.ResultsWe detected MOM in 65.9% controls and 54.0% cases. While we observed no overall association between MOM and endometrial cancer (HR=0.73, 95% CI: 0.47–1.15), we found a borderline significantly reduced rate of Type 1 endometrial cancer (HR=0.66, 95% CI: 0.39–1.00), but not other types of endometrial cancers (HR=1.00, 95% CI: 0.35–2.90). The reduced rate was not modified by hormonal exposure (P = 0.79). We found no association between MOM and risk of injuries (HR=0.96, 95% CI: 95% CI: 0.78–1.21).ConclusionsOur study suggests that MOM is inversely associated with Type 1 endometrial cancer, without evidence of an interaction with hormonal exposure. We encourage future research to confirm our findings.     

Lipid levels in midlife and risk of atrial fibrillation over 3 decades—Experience from the Swedish AMORIS cohort: A cohort study

BackgroundThe role of cholesterol levels in the development of atrial fibrillation (AF) is still controversial. In addition, whether and to what extent apolipoproteins are associated with the risk of AF is rarely studied. In this study, we aimed to investigate the association between blood lipid levels in midlife and subsequent risk of new-onset AF.Methods and findingsThis population-based study included 65,136 individuals aged 45 to 60 years without overt cardiovascular diseases (CVDs) from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort. Lipids were measured in 1985 to 1996, and individuals were followed until December 31, 2019 for incident AF (i.e., study outcome). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age, sex, and socioeconomic status. Over a mean follow-up of 24.2 years (standard deviation 7.5, range 0.2 to 35.9), 13,871 (21.3%) incident AF cases occurred. Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were statistically significantly associated with a lower risk of AF during the first 5 years of follow-up (HR = 0.61, 95% CI: 0.41 to 0.99, p = 0.013; HR = 0.64, 95% CI: 0.45 to 0.92, p = 0.016), but not thereafter (HR ranging from 0.94 [95% CI: 0.89 to 1.00, p = 0.038] to 0.96 [95% CI: 0.77 to 1.19, p > 0.05]). Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]). Apolipoprotein B (ApoB)/ApoA-I ratio was not associated with AF risk. The observed associations were similar among those who developed incident heart failure (HF)/coronary heart disease (CHD) and those who did not. The main limitations of this study include lack of adjustments for lifestyle factors and high blood pressure leading to potential residual confounding.ConclusionsHigh TC and LDL-C in midlife was associated with a lower risk of AF, but this association was present only within 5 years from lipid measurement and not thereafter. On the contrary, low HDL-C and ApoA-I and high TG/HDL-C ratio were associated with an increased risk of AF over almost 35 years of follow-up. ApoB/ApoA-I ratio was not associated with AF risk.

Mozhu Ding and colleagues investigate investigate the association between blood lipid levels in midlife and subsequent risk of new-onset atrial fibrillation in Sweden.     

Health conditions associated with metabolic syndrome after cancer at a young age: A nationwide register-based study

PurposeChildhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings.MethodsOur nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years.ResultsThe hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95%CI 3.1–7.0; HR 3.0, 95%1.5–6.1) and young adulthood (YA) cancer (HR 1.5, 95%CI 1.3–1.8; HR 1.6, 95%CI 1.1–2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95%CI 0.9–19.5) and YA cancer (HR 1.6, 95%CI 1.04–2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95%CI 3.7–10.3) and bone tumor (HR 4.3, 95%CI 1.9–9.4), and YA ALL (HR 4.8, 95%CI 3.1–7.0) and acute myeloid leukemia (AML) (HR 3.4, 95%CI 2.5–5.1) patients. Moreover, childhood ALL (HR 6.3, 95%CI 2.7–14.8), AML (HR 7.6, 95%CI 1.9–24.5) and central nervous system (CNS)-tumor (HR 3.5, 95%CI 1.3–9.2) and YA ALL (HR 3.7, 95%CI 1.2–9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings.ConclusionThe purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer.     

Predicting the Outcome of Sjogren’s Syndrome-Associated Non-Hodgkin’s Lymphoma Patients

BackgroundNon-Hodgkin''s lymphoma (NHL) development in Sjögren’s syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions.MethodsIn order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated.ResultsMALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14–95.80%) and the EFS was 77.92% (95% CI: 67.37–85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034–26.568) or for event (OR = 4.317, 95% CI: 1.146–9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772–11.637) and OS (HR = 5.946, 95% CI: 1.259–28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656–72.387 and OR = 12.589, 95% CI: 3.911–40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477–21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414–53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes.ConclusionsAt the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.     

Birth characteristics and risk of lymphoma in young children

BackgroundLymphoma is the third most common childhood malignancy and comprises two types, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The etiology of pediatric lymphomas is largely unknown, but has been suggested to have prenatal origins.MethodsIn this population-based study, California birth certificates were identified for 478 lymphoma cases diagnosed in children 0–5 years of age between 1988 and 2007; 208,015 controls frequency-matched by birth year were randomly selected from California birth records.ResultsCompared to non-Hispanic whites, Hispanic children had an increased risk of HL (odds ratio (OR) and 95% confidence interval (CI) 2.43 [1.14, 5.17]), and in particular, were diagnosed more often with the mixed cellularity subtype. For all types of lymphoma, we observed an about twofold risk increase with indicators for high risk pregnancies including tocolysis, fetopelvic disproportion and previous preterm birth. NHL risk doubled with the complication premature rupture of membranes (OR and 95% CI 2.18 [1.12, 4.25]) and HL with meconium staining of amniotic fluids (OR and 95% CI 2.55 [1.01, 6.43]).ConclusionThese data support previously reported associations between Hispanic ethnicity and HL and suggest that pregnancy related factors, such as intra-uterine infections and factors associated with preterm labor, may be involved in lymphoma pathogenesis.