| 1. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 3. |
- Jacobs, Kevin B, et al.
(author)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 4. |
- Adel Fahmideh, Maral, et al.
(author)
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A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk.
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R2 was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06-1.49], p=0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.
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| 5. |
- Adel Fahmideh, Maral, et al.
(author)
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Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility
- 2016
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In: Oncotarget. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 1949-2553.
-
Journal article (peer-reviewed)abstract
- Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7–19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression. The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratifid analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected. This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways.
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| 6. |
- Adel Fahmideh, Maral, et al.
(author)
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Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.
- 2018
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In: Clinical epidemiology. - 1179-1349. ; 10, s. 729-738
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Journal article (peer-reviewed)abstract
- Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring.The study was a population-based nested case-control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536).Compared with offspring of fathers aged 25-29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35-39 years (odds ratio [OR]=1.43 [95% CI 1.16-1.74]) and ≥40 years (OR =1.74 [95% CI 1.38-2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ≥40 years was OR =1.23 (95% CI 1.01-1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age.The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers.
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| 7. |
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| 9. |
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| 15. |
- Ahlbom, Anders, et al.
(author)
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Forskning om elöverkänslighet och andra effekter av elektromagnetiska fält; Åttonde årsrapporten
- 2011
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Reports (other academic/artistic)abstract
- Årets rapport diskuterar några forskningsområden där resultaten är av stor betydelse och som kan förväntas tilldra sig stor uppmärksamhet. Det första avser möjligheterna att skatta exponering och den relativa betydelsen av olika exponeringskällor. Viktigt arbete har där gjorts inom det Schweiziska nationella forskningsprogrammet. Vi har inkluderat en figur som på ett enkelt sätt sammanfattar viktiga och relevanta resultat avseende exponering i den allmänna miljön. Det framgår att basstationer, egen mobiltelefonanvändning och trådlösa hemtelefoner är de viktigaste källorna till exponering (om man bortser från lokal exponering till huvudet under samtal). Nästa område avser sömn och EEG-undersökningar. Det har där visat sig i ett antal undersökningar att elektromagnetiska fält tycks ha effekt på EEG under sömn. Effekterna är måttliga och kan storleksmässigt jämföras med vad som kan erhållas till exempel vid kaffe- eller alkoholintag. De tycks inte vara kopplade till subjektiv sömnkvalitet. Hur dessa effekter uppstår och vad de kan tänkas ha för betydelse är okänt. Men det är klart att det är angeläget att forskningen inom detta område fortsätter så att vi kan få denna effekt bekräftad om den är reell och ytterligare belyst och förstådd. Vi har också beskrivit en del ytterligare epidemiologisk forskning och framför allt slutrapporten från den så kallade Interphone-studien. Det har funnits förhoppningar om att denna studie skulle kunna ge definitivt besked i frågan om mobiltelefonanvändning och hjärntumörrisk. Men det stod redan efter publiceringen av de nationella rapporterna klart att så knappast skulle bli fallet. Rapporten har gett upphov till omfattande metodologiska diskussioner, vilka också varit orsaken till rapportens stora försening. Vår bedömning är att denna rapport inte ändrar våra tidigare bedömningar av risken för hjärntumör vid mobiltelefonanvändning, baserade bland annat på vad som framkommit i de nationella rapporterna. Däremot har denna rapport och andra rapporter från Interphone bidragit med viktiga metodologiska insikter. Vi diskuterar några ytterligare epidemiologiska undersökningar men inte heller de ändrar någonting i våra bedömningar. Slutligen presenterar vi nya riktlinjer för exponering från ”kraftfrekventa elektromagnetiska fält” från ICNIRP. De är baserade på en uppdaterad kunskapsgenomgång och på omfattande principdiskussioner. Bland annat har man nu bedömt att också fotofosfener (ljusblixtar) ska ingå bland kritiska effekter vilket i viss mån har påverkat gränsvärdena numeriskt. Detta har dock ingen praktisk betydelse för allmänhetens exponering därför att nivåerna ändå ligger flera storleksordningar över vad allmänheten normalt exponeras för. Det finns dock arbetsmiljöer där detta kan ha betydelse. En viktiga händelse under 2011 som redan nu kan förutses är att IARC (WHOs cancerforskningsinstitut) i maj ska ha ett så kallat monografimöte och ta ställning till hur sannolikt det är att radiofrekventa elektromagnetiska fält är cancerframkallande.
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| 16. |
- Ahlbom, Anders, et al.
(author)
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Occupational magnetic field exposure and myocardial infarction incidence.
- 2004
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In: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 15:4, s. 403-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Studies on healthy volunteers have seen reduced heart rate variability after exposure to extremely low-frequency electric and magnetic fields (EMF). Because reduced heart rate variability has been linked to cardiovascular disease risk, it has been hypothesized that exposure to EMF might increase the risk of cardiovascular disease. One epidemiologic study has shown increased mortality from cardiovascular conditions in utility workers with elevated exposure to magnetic fields, but several other epidemiologic studies have failed to confirm this result. We tested the hypothesis that occupational EMF exposure increases the risk of myocardial infarction in a large population-based case-control study of myocardial infarction, with detailed information on potential confounders. METHODS: We used data from the SHEEP study, which is a population-based case-control study of acute myocardial infarction in Stockholm. Occupational EMF exposure was based on job titles 1, 5, and 10 years before diagnosis. We used 2 approaches to classify exposure: first, specific individual job titles with presumed elevated EMF exposure, and second, classification of subjects according to a job-exposure matrix. RESULTS: We found no increased risk of myocardial infarction in subjects classified as having elevated EMF exposure. For the highest exposure category of > or = 0.3 microT according to the job-exposure matrix, the adjusted relative risk was = 0.57 (95% confidence interval = 0.36-0.89). CONCLUSIONS: The results of this study do not support the hypothesis that occupational EMF exposure increases the risk of myocardial infarction.
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| 17. |
- Ahlbom, Anders, et al.
(author)
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Radiofrequency electromagnetic fields and risk of disease and ill health - Research during the last ten years
- 2012
-
Reports (other academic/artistic)abstract
- The focus of this report is electromagnetic fields of the type that occur in connection with mobile telephony, so called radio frequency (RF) fields and the possibility that exposure to such fields poses a risk of disease or ill health. The purpose is to describe what was known ten years ago, what we have learned during the past decade, and where we stand today. TEN YEARS AGOThe mechanism of interaction between RF fields and the human body was established long ago and is increased temperature of exposed tissue (compare microwave ovens). Methods for measurements of the fields in the air were developed early but the data on distribution of the absorbed energy in the human body was still restricted. Data regarding sources and levels of exposure to the population was limited because systematic measurements had not been conducted. A considerable number of provocation studies on exposure to fields of lower frequencies (related to electric power and computer screens) had already been conducted and had not found any evidence of an association to symptoms (headache, vertigo, dizziness, concentration difficulties, insomnia) but the corresponding information about RF fields and occurrence of symptoms was scarce. Few and methodologically limited epidemiological studies had been conducted on RF field exposure and cancer.WHAT WAS LEARNED DURING THE PAST TEN YEARSExtensive research on various aspects of RF fields has been conducted during the last ten years and the knowledge database has increased considerably. Simulation models have improved our knowledge about how the fields and the energy are distributed in the body. Mobile, so called, exposimeters have been developed for use in epidemiological studies. Many more measurements have been conducted to increase our knowledge about sources and level of exposure to the population. More than 15 provocation studies (single or double blind) have been conducted on symptoms attributed to exposure to RF fields. These studies have not been able to demonstrate that people experience symptoms or sensations more often when the fields are turned on than when they are turned off. One longitudinal study has looked at frequency of symptoms in relation to environmental exposure and this study found no association between exposure and symptoms. A considerable number of studies on cancer, and in particular brain tumor, were presented. As a consequence there exist now very useful data including methodological results that can be used in the interpretation of this research. With a small number of exceptions the available results are all negative and taken together with new methodological understandings the overall interpretation is that these do not provide support for an association between mobile telephony and brain tumor risk. In addition, national cancer statistics are very useful sources of information because mobile phone usage has increased so quickly. Had mobile phone use and brain cancer risk been associated it would have been visible as an increasing trend in national cancer statistics. But brain cancer rates are not increasing. WHERE WE STAND TODAYWe now know much more about measurements and absorption of RF fields and also about sources of exposure to the population and levels of exposure. A considerable number of provocation studies on RF exposure and symptoms have been unable to show any association. Overall, the data on brain tumor and mobile telephony do not support an effect of mobile phone use on tumor risk, in particular when taken together with national cancer trend statistics throughout the world. Research on mobile telephony and health started without a biologically or epidemiologically based hypothesis about possible health risks. Instead the inducement was an unspecific concern related to a new and rapidly spreading technology. Extensive research for more than a decade has not detected anything new regarding interaction mechanisms between radiofrequency fields and the human body and has found no evidence for health risks below current exposure guidelines. While absolute certainty can never be achieved, nothing has appeared to suggest that the since long established interaction mechanism of heating would not suffice as basis for health protection.
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| 18. |
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| 19. |
- Andel, Ross, et al.
(author)
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Work-related exposure to extremely low-frequency magnetic fields and dementia: results from the population-based study of dementia in Swedish twins.
- 2010
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 65:11, s. 1220-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: We examined the association between extremely low-frequency magnetic fields (EMF) and the risk of dementia and Alzheimer's disease using all 9,508 individuals from the Study of Dementia in Swedish Twins (HARMONY) with valid occupational and diagnostic data. METHODS: Dementia diagnoses were based on telephone screening followed by in-person clinical workup. Main lifetime occupation was coded according to an established EMF exposure matrix. Covariates were age, gender, education, vascular risk factors, and complexity of work. Based on previous research, data were also analyzed separately for cases with disease onset by age 75 years versus later, men versus women, and those with manual versus nonmanual main occupation. We used generalized estimating equations with the entire sample (to adjust for the inclusion of complete twin pairs) and conditional logistic regression with complete twin pairs only. RESULTS: Level of EMF exposure was not significantly associated with dementia or Alzheimer's disease. However, in stratified analyses, medium and high levels of EMF exposure were associated with increased dementia risk compared with low level in cases with onset by age 75 years (odds ratio: 1.94, 95% confidence interval: 1.07-3.65 for medium, odds ratio: 2.01, 95% confidence interval: 1.10-3.65 for high) and in participants with manual occupations (odds ratio: 1.81, 95% confidence interval: 1.06-3.09 for medium, odds ratio: 1.75, 95% confidence interval: 1.00-3.05 for high). Results with 42 twin pairs discordant for dementia did not reach statistical significance. CONCLUSIONS: Occupational EMF exposure appears relevant primarily to dementia with an earlier onset and among former manual workers.
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| 20. |
- Andersson, Ulrika, et al.
(author)
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A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
- 2010
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 12, s. 17-17
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Journal article (peer-reviewed)abstract
- Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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| 21. |
- Andersson, Ulrika, et al.
(author)
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MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.
- 2009
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In: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 125:4, s. 968-972
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Journal article (peer-reviewed)abstract
- The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations.
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| 22. |
- Aydin, Denis, et al.
(author)
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Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.
- 2011
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 103:16, s. 1264-76
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Journal article (peer-reviewed)abstract
- It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents.
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| 23. |
- Bethke, Lara, et al.
(author)
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CASP8 D302H and meningioma risk : an analysis of five case-control series
- 2009
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In: Cancer Letters. - Clare : Elsevier. - 0304-3835 .- 1872-7980. ; 273:2, s. 312-315
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Journal article (peer-reviewed)abstract
- Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.
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| 24. |
- Bethke, Lara, et al.
(author)
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Comprehensive analysis of DNA repair gene variants and risk of meningioma
- 2008
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:4, s. 270-276
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Journal article (peer-reviewed)abstract
- Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility.Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case–control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided.Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1–interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 × 10−6; P = .009 after adjusting for multiple testing).Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.
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| 25. |
- Bethke, Lara, et al.
(author)
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Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma
- 2008
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 17:6, s. 800-805
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Journal article (peer-reviewed)abstract
- Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case–control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case–control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14–1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.
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| 26. |
- Bethke, Lara, et al.
(author)
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Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
- 2008
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:5, s. 1195-1202
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Journal article (peer-reviewed)abstract
- Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.
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| 27. |
- Bethke, Lara, et al.
(author)
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The Common D302H Variant of CASP8 Is Associated with Risk of Glioma
- 2008
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:4, s. 987-989
-
Journal article (peer-reviewed)abstract
- Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.
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| 28. |
- Bonnard, Åsa, et al.
(author)
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The risk of cholesteatoma in individuals with first-degree relatives surgically treated for the disease
- 2023
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In: JAMA Otolaryngology - Head and Neck Surgery. - : American Medical Association (AMA). - 2168-6181 .- 2168-619X. ; 149:5
-
Journal article (peer-reviewed)abstract
- 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.
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| 29. |
- Brooke, Hannah L, et al.
(author)
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Adult children's socioeconomic resources and mothers' survival after a breast cancer diagnosis : a Swedish population-based cohort study.
- 2017
-
In: BMJ Open. - : BMJ. - 2044-6055. ; 7:3
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Socioeconomic inequalities in survival after breast cancer persist worldwide. We aim to determine whether adult offspring's socioeconomic resources contribute to inequalities in mothers' survival after breast cancer.METHODS: 14 231 women, aged 65-79 years, with a child aged ≥30 years and a first primary diagnosis of breast cancer in the National Cancer Register between 2001 and 2010 were followed until death, 10 years after diagnosis, or end of study (December 2015). Relative survival proportions and excess mortality within 10 years of diagnosis by strata of offspring's education level and disposable income were estimated using flexible parametric models accounting for measures of mothers' socioeconomic position and expected mortality in the general population.RESULTS: 4292 women died during 102 236 person-years of follow-up. Crude 10-year relative survival proportions for mothers of children with >14, 12-14 and <12 years of education were 0.89 (0.87 to 0.91), 0.87 (0.85 to 0.89) and 0.79 (0.76 to 0.81), respectively. Compared with mothers of children with >14 years of education, mothers of children with <12 or 12-14 years of education had substantially higher excess mortality (excess HR 1.69 (1.38 to 2.07) and 1.22 (1.00 to 1.48), respectively). Higher mortality did not differ between tertiles of offspring's disposable income.CONCLUSIONS: Adult offspring's education level may contribute to inequalities in mothers' survival after breast cancer. Clinicians should be aware of the educational context beyond the individual and women with less educated offsprings may require extra support. This should be considered in future research, policy frameworks and interventions aimed at reducing survival inequalities.
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| 30. |
- Brooke, Hannah L, et al.
(author)
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Methodological choices affect cancer incidence rates : a cohort study.
- 2017
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In: Population Health Metrics. - : Springer Science and Business Media LLC. - 1478-7954. ; 15:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Incidence rates are fundamental to epidemiology, but their magnitude and interpretation depend on methodological choices. We aimed to examine the extent to which the definition of the study population affects cancer incidence rates.METHODS: All primary cancer diagnoses in Sweden between 1958 and 2010 were identified from the national Cancer Register. Age-standardized and age-specific incidence rates of 29 cancer subtypes between 2000 and 2010 were calculated using four definitions of the study population: persons resident in Sweden 1) based on general population statistics; 2) with no previous subtype-specific cancer diagnosis; 3) with no previous cancer diagnosis except non-melanoma skin cancer; and 4) with no previous cancer diagnosis of any type. We calculated absolute and relative differences between methods.RESULTS: Age-standardized incidence rates calculated using general population statistics ranged from 6% lower (prostate cancer, incidence rate difference: -13.5/100,000 person-years) to 8% higher (breast cancer in women, incidence rate difference: 10.5/100,000 person-years) than incidence rates based on individuals with no previous subtype-specific cancer diagnosis. Age-standardized incidence rates in persons with no previous cancer of any type were up to 10% lower (bladder cancer in women) than rates in those with no previous subtype-specific cancer diagnosis; however, absolute differences were <5/100,000 person-years for all cancer subtypes.CONCLUSIONS: For some cancer subtypes incidence rates vary depending on the definition of the study population. For these subtypes, standardized incidence ratios calculated using general population statistics could be misleading. Moreover, etiological arguments should be used to inform methodological choices during study design.
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| 31. |
- Brooke, Hannah L, et al.
(author)
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Socioeconomic position and incidence of colorectal cancer in the Swedish population.
- 2016
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In: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 40, s. 188-95
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Journal article (peer-reviewed)abstract
- BACKGROUND: The association between socioeconomic position and incidence of colorectal cancer is inconsistent and differs by global region. We aimed to clarify this association in the Swedish population.METHODS: We conducted a population-based open cohort study using data from Swedish national registers. We included all individuals, aged ≥30 years, residing in Sweden between 1993 and 2010. Socioeconomic position was indicated by (1) highest educational level (five groups), and (2) disposable income (quintiles). We used Poisson regression to estimate incidence rate ratios (IRR) and 95% confidence intervals (95% CI) of colon and rectal cancer, and colon and rectal dysplasia.RESULTS: In total, 97,827,817 person-years were accumulated and 82,686 cases of colorectal cancer were diagnosed. Compared to men with 'higher secondary' education, the adjusted IRRs (95% CI) of rectal cancer in men with 'primary or less', 'lower secondary', 'lower university' or 'higher university' education were: 1.06 (1.00, 1.11), 1.05 (0.99, 1.10), 0.96 (0.89, 1.03), and 0.92 (0.86, 0.98), respectively. In women, the corresponding figures were: 1.04 (0.95, 1.14), 1.03 (0.94, 1.13), 0.92 (0.82, 1.02) and 0.92 (0.82, 1.02). Disposable income was not associated with rectal cancer incidence. Adjusted IRRs of colon cancer did not differ between levels of education or disposable income overall or for specific colon sub-sites. Neither education nor disposable income was consistently associated with incidence of colon or rectal dysplasia.CONCLUSIONS: Prevention strategies for colon cancer should be applicable to individuals regardless of their socioeconomic position. However, factors conferred by education, e.g., health awareness, may be important for approaches aiming to reduce inequalities in incidence of rectal cancer. Further evaluation of cancer prevention and health promotion strategies among less educated groups is warranted.
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| 32. |
- Brooke, Hannah Louise, et al.
(author)
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The Swedish cause of death register
- 2017
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In: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 32:9, s. 765-773
-
Journal article (peer-reviewed)abstract
- 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.
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| 33. |
- Dahlin, Anna M., 1979-, et al.
(author)
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A genome-wide association study on medulloblastoma
- 2020
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In: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315
-
Journal article (peer-reviewed)abstract
- Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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| 34. |
- Deleskog, Anna, et al.
(author)
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Maternal diabetes and incidence of childhood cancer : a nationwide cohort study and exploratory genetic analysis
- 2017
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In: Clinical Epidemiology. - 1179-1349. ; 9, s. 633-642
-
Journal article (peer-reviewed)abstract
- Background: The etiology of childhood cancer is not well understood, but may be linked to prenatal and perinatal factors, such as maternal diabetes. However, this association has not been examined in depth. We aimed to determine if maternal diabetes is associated with risk of childhood brain tumor (CBT), leukemia (all types combined and acute lymphoblastic leukemia [ALL] separately), and lymphoma.Methods: All children born in Sweden between 1973 and 2014 (n= 4,239,965) were followed from birth until first cancer diagnosis, age 15 years, or December 31, 2015. Data on maternal diabetes, childhood cancer, and covariates were obtained from nationwide health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using Cox regression adjusted for potential confounders/mediators. Additionally, we performed an exploratory analysis using results from published genome-wide association studies and functional annotation.Results: Maternal diabetes was associated with lower risk of CBT (adjusted IRR [95% CI]: 0.56 [0.35-0.91]) and higher risk of leukemia (adjusted IRR: 1.47 [1.13-1.92] for all leukemia combined and 1.64 [1.23-2.18] for ALL). These associations were similar for both maternal type 1 diabetes and gestational diabetes. Associations of five previously identified genetic loci were compatible with a causal effect of diabetes traits on neuroblastoma and common Hodgkin's lymphoma.Conclusion: Children whose mother had diabetes had lower risk of CBT and higher risk of leukemia, compared with children whose mother did not have diabetes. Our results are compatible with a role of prenatal and perinatal glycemic environment in childhood cancer etiology.
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| 35. |
- Dobbins, Sara E., et al.
(author)
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Common variation at 10p12.31 near MLLT10 influences meningioma risk
- 2011
-
In: Nature Genetics. - London : Nature America, Inc.. - 1061-4036 .- 1546-1718. ; 43:9, s. 825-827
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Journal article (peer-reviewed)abstract
- To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.
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| 36. |
- Fang, Fang, et al.
(author)
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Amyotrophic lateral sclerosis among cross-country skiers in Sweden.
- 2016
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 31:3, s. 247-253
-
Journal article (peer-reviewed)abstract
- A highly increased risk of amyotrophic lateral sclerosis (ALS) has been suggested among professional athletes. We aimed to examine whether long distance cross-country skiers have also a higher risk of ALS and whether the increased risk was modified by skiing performance. We followed 212,246 cross-country skiers in the Swedish Vasaloppet cohort and a random selection of 508,176 general Swedes not participating in the Vasaloppet during 1989-2010. The associations between cross-country skiing as well as skiing performance (i.e., type of race, finishing time and number of races) and the consequent risk of ALS were estimated through hazard ratios (HRs) derived from Cox model. During the study, 39 cases of ALS were ascertained among the skiers. The fastest skiers (100-150 % of winner time) had more than fourfold risk of ALS (HR 4.31, 95 % confidence interval [CI] 1.78-10.4), as compared to skiers that finished at >180 % of winner time. Skiers who participated >4 races during this period had also a higher risk (HR 3.13, 95 % CI 1.37-7.17) than those participated only one race. When compared to the non-skiers, the fastest skiers still had a higher risk (HR 2.08, 95 % CI 1.12-3.84), as skiers who had >4 races (HR 1.88, 95 % CI 1.05-3.35), but those finishing at >180 % of winner time had a lower risk (HR 0.46, 95 % CI 0.24-0.87). In conclusion, long distance cross-country skiing is associated with a higher risk of ALS, but only among the best skiers; recreational skiers appear to have a largely reduced risk.
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| 37. |
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| 38. |
- Fisher, James L., et al.
(author)
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Loud Noise Exposure and Acoustic Neuroma
- 2014
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 180:1, s. 58-67
-
Journal article (peer-reviewed)abstract
- The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.
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| 39. |
- Frederiksen, Line Elmerdahl, et al.
(author)
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Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden : a register-based cohort study from the SALiCCS research programme
- 2022
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In: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 69
-
Journal article (peer-reviewed)abstract
- Background: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. Methods: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. Findings: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3–16·5) for childhood cancer survivors, 14·0% (13·5–14·5) for siblings, and 12·7% (12·4–12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31–1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28–1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. Interpretation: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. Funding: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.
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| 40. |
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| 41. |
- Khanolkar, Amal R, et al.
(author)
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Socioeconomic position and the risk of brain tumour : a Swedish national population-based cohort study.
- 2016
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In: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:12, s. 1222-1228
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim was to investigate associations between different measures of socioeconomic position (SEP) and incidence of brain tumours (glioma, meningioma and acoustic neuroma) in a nationwide population-based cohort.METHODS: We included 4 305 265 individuals born in Sweden during 1911-1961, and residing in Sweden in 1991. Cohort members were followed from 1993 to 2010 for a first primary diagnosis of brain tumour identified from the National Cancer Register. Poisson regression was used to compute incidence rate ratios (IRR) by highest education achieved, family income, occupational group and marital status, with adjustment for age, healthcare region of residence, and time period.RESULTS: We identified 5735 brain tumours among men and 7101 among women during the study period. Highly educated men (≥3 years university education) had increased risk of glioma (IRR 1.22, 95% CI 1.08 to 1.37) compared to men with primary education. High income was associated with higher incidence of glioma in men (1.14, 1.01 to 1.27). Women with ≥3 years university education had increased risk of glioma (1.23, 1.08 to 1.40) and meningioma (1.16, 1.04 to 1.29) compared to those with primary education. Men and women in intermediate and higher non-manual occupations had increased risk of glioma compared to low manual groups. Compared to those married/cohabiting, being single or previously married/cohabiting was associated with decreased risk of glioma in men. Men in non-manual occupations had ∼50% increased risk of acoustic neuroma compared to men in low manual occupations.CONCLUSIONS: We observed consistent associations between higher SEP and higher risk of glioma. Completeness of cancer registration and detection bias are potential explanations for the findings.
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| 42. |
- Kitahara, Cari M., et al.
(author)
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Association between adult height, genetic susceptibility and risk of glioma
- 2012
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 41:4, s. 1075-1085
-
Journal article (peer-reviewed)abstract
- Background Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub- types, and investigated effect modification by genetic susceptibility to the disease. Methods We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. Results Among men, we found a positive association between height and glioma risk (epsilon 190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (epsilon 175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. Conclusion An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease.
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| 43. |
- Kitahara, Cari M., et al.
(author)
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Personal History of Diabetes, Genetic Susceptibility to Diabetes, and Risk of Brain Glioma : A Pooled Analysis of Observational Studies
- 2014
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:1, s. 47-54
-
Journal article (peer-reviewed)abstract
- Background: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk associated single-nucleotide polymorphisms(SNP). We also examined the associations between 13 diabetes risk associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted logistic regression models. Results: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes related SNPs examined in relation to glioma risk. Conclusion: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association. Impact: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma.
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| 44. |
- Kiuru, Anne, et al.
(author)
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XRCC1 and XRCC3 variants and risk of glioma and meningioma
- 2008
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In: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 88, s. 135-142
-
Journal article (peer-reviewed)abstract
- Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.
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| 45. |
- Lagergren, Jesper, et al.
(author)
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Marital status, education, and income in relation to the risk of esophaegal and gastric cancer by histological type and site
- 2016
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In: Cancer. - Stockholm : Wiley. - 0008-543X .- 1097-0142. ; 122:2, s. 207-212
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Journal article (peer-reviewed)abstract
- BACKGROUNDMarital status, income, and education might influence the risk of esophageal and gastric cancer, but the literature is limited. A large study addressing subtypes of these tumors was used to clarify these associations.METHODSA nationwide, Swedish population–based cohort study from 1991 to 2010 included individuals who were 50 years old or older. Data on exposures, covariates, and outcomes were obtained from well-maintained registers. Four esophagogastric tumor subtypes were analyzed in combination and separately: esophageal adenocarcinoma, esophageal squamous cell carcinoma, cardia adenocarcinoma, and noncardia gastric adenocarcinoma. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Analyses were stratified by sex and adjusted for confounders.RESULTSAmong 4,734,227 participants (60,634,007 person-years), 24,095 developed esophageal or gastric cancer. In comparison with individuals in a long marriage, increased IRRs were found among participants who were in a shorter marriage or were never married, remarried, divorced, or widowed. These associations were indicated for each tumor subtype but were generally stronger for esophageal squamous cell carcinoma. Higher education and income were associated with decreased IRRs in a seemingly dose-response manner and similarly for each subtype. In comparison with the completion of only primary school, higher tertiary education rendered an IRR of 0.64 (95% CI, 0.60-0.69) for men and an IRR of 0.68 (95% CI, 0.61-0.75) for women. Comparing participants in the highest and lowest income brackets (highest 20% vs lowest 20%) revealed an IRR of 0.74 (95% CI, 0.70-0.79) for men and an IRR of 0.83 (95% CI, 0.76-0.91) for women.CONCLUSIONSDivorce, widowhood, living alone, low educational attainment, and low income increase the risk of each subtype of esophageal and gastric cancer. These associations require attention when high-risk individuals are being identified.
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| 47. |
- Liu, Qianwei, et al.
(author)
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Suicide attempt and death by suicide among parents of young individuals with cancer : A population-based study in Denmark and Sweden
- 2024
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 21:1
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Journal article (peer-reviewed)abstract
- BackgroundThe 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 findingsWe 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.ConclusionsIn 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.
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| 48. |
- Lonn, Stefan, et al.
(author)
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Long-term mobile phone use and brain tumor risk
- 2005
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 161:6, s. 526-535
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Journal article (peer-reviewed)abstract
- Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population-based, case-control study was to test the hypothesis that long-term mobile phone use increases the risk of brain tumors. The authors identified all cases aged 20-69 years who were diagnosed with glioma or meningioma during 2000-2002 in certain parts of Sweden. Randomly selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar results were found for more than 10 years' duration of mobile phone use. No risk increase was found for ipsilateral phone use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor histology, type of phone, and amount of use. This study includes a large number of long-term mobile phone users, and the authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma.
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| 49. |
- Lonn, Stefan, et al.
(author)
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Mobile phone use and risk of parotid gland tumor
- 2006
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 164:7, s. 637-643
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Journal article (peer-reviewed)abstract
- Handheld mobile phones were introduced in Denmark and Sweden during the late 1980s. This makes the Danish and Swedish populations suitable for a study aimed at testing the hypothesis that long-term mobile phone use increases the risk of parotid gland tumors. In this population-based case-control study, the authors identified all cases aged 20-69 years diagnosed with parotid gland tumor during 2000-2002 in Denmark and certain parts of Sweden. Controls were randomly selected from the study population base. Detailed information about mobile phone use was collected from 60 cases of malignant parotid gland tumors (85% response rate), 112 benign pleomorphic adenomas (88% response rate), and 681 controls (70% response rate). For regular mobile phone use, regardless of duration, the risk estimates for malignant and benign tumors were 0.7 (95% confidence interval: 0.4, 1.3) and 0.9 (95% confidence interval: 0.5, 1.5), respectively. Similar results were found for more than 10 years' duration of mobile phone use. The risk estimate did not increase, regardless of type of phone and amount of use. The authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of parotid gland tumors.
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