BackgroundThe Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR.Methods and resultsIn January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%.ConclusionsIn conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.

Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-017-0316-1) contains supplementary material, which is available to authorized users.

To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 × 10−17), 8q24.21 (rs4295627, CCDC26; P = 2.34 × 10−18), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 × 10−15), 20q13.33 (rs6010620, RTEL1; P = 2.52 × 10−12) and 11q23.3 (rs498872, PHLDB1; P = 1.07 × 10−8). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10−8). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10−11). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases.

It is now twenty years since Wertheimer and Leeper (1979) published the first study suggesting an association between residential exposure to extremely low frequency magnetic fields (EMF) and childhood cancer. Ever since, this has been a controversial issue with the findings from several, but not all, subsequent epidemiological studies being consistent with an association, particularly with respect to residential exposure and childhood leukaemia (Portier and Wolfe, 1998). However, many of the reports have been based on small numbers of exposed cases, and despite intense experimental research no known biophysical mechanism to explain an effect has been established.We conducted a pooled analysis based on primary data from nine studies on EMF and childhood leukaemia, addressing three specific questions:1. Do the combined results of these studies indicate that there is an association between EMF exposure and childhood leukaemia risk, which is larger than one would expect from random variability?2. Does adjustment for confounding from socioeconomic class, mobility, level of urbanization, detached/not detached dwelling, and level of traffic exhaust change the results? 3. Do the combined data support the existence of the so-called wire code paradox, that is, a stronger association between proxy measures of EMF and cancer than between direct measurements and cancer? METHODSThe original plan for this project was to include all European studies that addressed the question of an association between EMF and childhood leukaemia and were based on either 24 or 48 hour magnetic field measurements or calculated fields. At the time five such studies were reported (Feychting and Ahlbom, 1993; Olsen et al, 1993;Verkasalo et al, 1993;Tynes and Haldorsen, 1997;Michaelis et al, 1998). In addition, a nationwide childhood cancer study was in progress and near completion in the UK (UKCCS, 1999). Since we were not aware of any other European study to be published in the near future, the inclusion of the UK study would give us a complete set of European studies. We felt that if we could also incorporate new studies from non-European countries this pooled analysis would be up to date and presumably stay current for several years. We were aware of three more studies in other parts of the world with compatible information that were all nearly A pooled analysis of magnetic fields and childhood leukaemia Summary Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukae...

SummaryBackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14...

A case-control study was conducted to test the hypothesis that exposure to magnetic fields of the type generated by high-voltage power lines increases cancer incidence in children. The study base consisted of everyone under age 16 years who had lived on a property located within 300 meters of any of the 220 and 400 kV power lines in Sweden during the period 1960-1985. Subjects were followed from their entry into the study base through 1985. A total of 142 cancer cases were identified through a record linkage to the Swedish Cancer Registry. There were 39 leukemia and 33 central nervous system tumor cases. A total of 558 controls were selected at random from the study base. Exposure was assessed by spot measurements and by calculations of the magnetic fields generated by the power lines, taking distance, line configuration, and load into account. Information about historical loads on the power lines was used to calculate the magnetic fields for the year closest in time to diagnosis. When historical calculations were used as exposure assessment for childhood leukemia with cutoff points at 0.1 and 0.2 microtesla (microT), the estimated relative risk increased over the two exposure levels and was estimated at 2.7 (95% confidence interval (CI) 1.0-6.3) for 0.2 microT and over; p for trend = 0.02. When the upper cutoff point was shifted to 0.3 microT, the relative risk was 3.8 (95% CI 1.4-9.3); p for trend = 0.005. These results persisted when adjustment for potential confounding factors was made. For central nervous system tumor, lymphoma, and all childhood cancers combined, there was no support for an association.

The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case-control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifiBaruch Modan is deceased. 123Eur J Epidemiol (2007) 22: 647-664 DOI 10.1007/s10654-007-9152-z cally, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case-control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.