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Sökning: WFRF:(Hjalgrim Henrik)

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1.
  • Edgren, Gustaf, et al. (författare)
  • The new Scandinavian Donations and Transfusions database (SCANDAT2) : a blood safety resource with added versatility
  • 2015
  • Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 55:7, s. 1600-1606
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundRisks of transfusion-transmitted disease are currently at a record low in the developed world. Still, available methods for blood surveillance might not be sufficient to detect transmission of diseases with unknown etiologies or with very long incubation periods. Study Design and MethodsWe have previously created the anonymized Scandinavian Donations and Transfusions (SCANDAT) database, containing data on blood donors, blood transfusions, and transfused patients, with complete follow-up of donors and patients for a range of health outcomes. Here we describe the re-creation of SCANDAT with updated, identifiable data. We collected computerized data on blood donations and transfusions from blood banks covering all of Sweden and Denmark. After data cleaning, two structurally identical databases were created and the entire database was linked with nationwide health outcomes registers to attain complete follow-up for up to 47 years regarding hospital care, cancer, and death. ResultsAfter removal of erroneous records, the database contained 25,523,334 donation records, 21,318,794 transfusion records, and 3,692,653 unique persons with valid identification, presently followed over 40 million person-years, with possibility for future extension. Data quality is generally high with 96% of all transfusions being traceable to their respective donation(s) and a very high (>97%) concordance with official statistics on annual number of blood donations and transfusions. ConclusionsIt is possible to create a binational, nationwide database with almost 50 years of follow-up of blood donors and transfused patients for a range of health outcomes. We aim to use this database for further studies of donor health, transfusion-associated risks, and transfusion-transmitted disease.
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2.
  • Edgren, Gustaf, et al. (författare)
  • Transmission of Neurodegenerative Disorders Through Blood Transfusion A Cohort Study
  • 2016
  • Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 165:5, s. 316-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications. Objective: To investigate possible transfusion transmission of neurodegenerative disorders. Design: Retrospective cohort study. Setting: Nationwide registers of transfusions in Sweden and Denmark. Participants: 1 465 845 patients who received transfusions between 1968 and 2012. Measurements: Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. Results: Among included patients, 2.9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors was 1.04 (95% CI, 0.99 to 1.09). Corresponding estimates for Alzheimer disease and Parkinson disease were 0.99 (CI, 0.85 to 1.15) and 0.94 (CI, 0.78 to 1.14), respectively. Hepatitis transmission was detected before but not after implementation of hepatitis C virus screening. Limitation: Observational study design, underascertainment of the outcome, and possible insufficient statistical power. Conclusion: The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare.
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3.
  • Englund, Annika, et al. (författare)
  • Hodgkin lymphoma in children, adolescents and young adults - a comparative study of clinical presentation and treatment outcome.
  • 2018
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 57:2, s. 276-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hodgkin lymphoma (HL) treatment protocols for children, adolescents and young adults traditionally differ, but the biological and clinical justification for this remains uncertain.Material and methods: We compared age-dependent clinical presentation and treatment and outcome for 1072 classical HL patients 0–24 years diagnosed in Denmark (1990–2010) and Sweden (1992–2009) in pediatric (n = 315, Denmark <15 years, Sweden <18 years) or adult departments (n = 757). Distribution of clinical characteristics was assessed with Pearson’s chi2-test and Mantel–Haenszel trend test. The Kaplan–Meier method was used for survival analyses. Hazard ratios (HR) were used to compare the different treatment groups and calculated using Cox regression.Results: Children (0–9 years) less often presented with advanced disease than adolescents (10–17 years) and young adults (18–24 years) (stage IIB-IV: children 32% vs. adolescents 50%, and adults 55%; p < .005). No variation in overall survival (OS) was seen between pediatric and adult departments or by country. Danish pediatric patients received radiotherapy (36%) less frequently than Swedish pediatric patients (71%) (p < .0001). Ten-year event-free survival (EFS) was lower among Danish pediatric patients (0–14 years) (0.79; 95% confidence interval (CI) 0.70–0.86) than among Swedish pediatric patients (0–17 years) (0.88; 95% CI 0.83–0.92), HR (1.93; 95% CI 1.08–3.46). A similar pattern was seen between adult patients in the two countries: Denmark 10-year EFS 0.85 (95% CI 0.81–0.88), Sweden 0.88 (95% CI 0.84–0.91), adjusted HR 1.51 (95% CI 1.03–2.22).Conclusion: Adolescents and young adults shared similar clinical presentation suggesting a rationale of harmonized treatment for these groups. Both adult and pediatric protocols provided high OS with no significant difference between the departments. The less frequent use of radiotherapy in Danish pediatric patients corresponded to a lower EFS, but comparable OS in all groups confirmed effective rescue strategies for the relapsing patients.
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6.
  • Glimelius, Ingrid, 1975-, et al. (författare)
  • Distribution of hospital care among pediatric and young adult Hodgkin lymphoma survivors : A population-based cohort study from Sweden and Denmark
  • 2019
  • Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 8:10, s. 4918-4927
  • Tidskriftsartikel (refereegranskat)abstract
    • The burden of late effects among Hodgkin lymphoma (HL) survivors treated according to contemporary protocols remains poorly characterized. We used nation-wide registers to assess number of inpatient bed-days and specialist outpatient visits among 1048 HL-patients (<25 years, diagnosed 1990-2010) and 5175 country-, sex-, and age-matched comparators. We followed them for up to 24 years, with time-dependent assessment of relapse status. International Classification of Diseases (ICD-10) chapter-specific hazard ratios (HRs) were assessed in Cox regression analyses, and nonparametric statistics described patterns of health-care-use. Relative to comparators, relapse-free survivors were at increased risk of infections, diseases of the blood, endocrine, circulatory and respiratory systems, and unspecific symptoms, HRs ranging from 1.86 to 3.05. Relative to comparators, relapsed survivors had at statistically significantly increased risk of diseases reflecting practically all investigated disease-chapters, HRs ranging from 1.60 to 18.7. Among relapse-free survivors, 10% of the patients accounted for 80% of all hospital bed days, and 55% were never hospitalized during follow-up. Among relapsed-survivors, 10% of the patients accounted for 50% of the bed days, and only 24% were never hospitalized during follow-up. In contrast, 10% of the comparators accounted for 90% of hospital bed days and 75% were never hospitalized. These findings challenge the impression of a uniformly distributed long-term morbidity among all HL survivors and emphasize the need for early identification and attention to patients particularly susceptible to late effects, such as relapsed survivors.
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7.
  • Halmin, Marit, et al. (författare)
  • Epidemiology of Massive Transfusion : A Binational Study From Sweden and Denmark
  • 2016
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 44:3, s. 468-477
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. Design: Descriptive cohort study. Setting: Nationwide study with data from Sweden and Denmark. Patients: The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. Measurements and Main Results: Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. Conclusions: This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field.
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  • Hjalgrim, Lisa Lyngsie, et al. (författare)
  • Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and Iceland
  • 2004
  • Ingår i: Journal of the National Cancer Institute. - Cary : Oxford University Press. - 0027-8874 .- 1460-2105. ; 96:20, s. 1549-1556
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Compelling evidence suggests that childhood leukemia often originates in utero. Birth weight is one of the few pregnancy-related risk factors that has been associated with leukemia risk, but the association has remained poorly characterized. We conducted a population-based case-control stud-v in Denmark, Sweden, Norway, and Iceland to investigate the association between birth weight (and other birth characteristics) and the risk of childhood leukemia.Methods: Overall, 1905 children (aged 0-14 years) with acute lymphoblastic leukemia (ALL) and 299 children with acute myeloid leukemia (AML) diagnosed between January 1, 1984, and December 31, 1999, were identified in the Nordic Society of Paediatric Haematology and Oncology acute leukemia database. Each case patient was matched to five population control subjects (n = 1.0 745) on nationality, age, and sex. All live-born siblings of case patients (n = 3812) and control subjects (n = 17 937) were also identified in population registers. Information on birth weight and gestational age at birth was ascertained from the national Medical Birth Registers. The association between various birth characteristics and leukemia risk was assessed by conditional logistic regression. All statistical tests were two-sided.Results: Risk of ALL overall was statistically significantly associated with birth weight (odds ratio [OR] = 1.26 per 1-kg increase in birth weight, 95% confidence interval [CI] = 1.13 to 1.41). The association was similar for B- and T-lineage ALL and across all diagnostic ages (0-14 years). However, children with ALL did not weigh more at birth than their siblings. Statistically significantly reduced risks of B-precursor ALL were observed with increasing position in the birth order (OR = 0.90 per position increase, 95% CI = 0.84 to 0.96) and increasing gestational age (OR = 0.87 per 2-week increase in gestational age, 95% CI = 0.81 to 0.94). Risk of AML did not vary monotonically with birth weight, and low birth weight (<1500 g [i.e., 3.3 pounds]) was associated with the highest risk.Conclusion: Our results are compatible with the hypothesis that a high birth weight is associated with an increased risk of ALL.
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9.
  • Moslemi, Camous, et al. (författare)
  • A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID-19 susceptibility, severity, and long COVID-19
  • 2023
  • Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 63:1, s. 47-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well. Study design and methods: To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates. Results: The Lewis blood group antigen Lea displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79–0.93] p <.001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06–1.14] p <.001, 1.17 CI[1.14–1.2] p <.001, and 1.2 CI[1.14–1.26] p <.001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found. Discussion: This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS-CoV-2.
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10.
  • Moslemi, Camous, et al. (författare)
  • Genetic prediction of 33 blood group phenotypes using an existing genotype dataset
  • 2023
  • Ingår i: Transfusion. - 0041-1132. ; 63:12, s. 2297-2310
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. Study Design and Methods: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. Results: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa/Cob, Doa/Dob, E/e, Jka/Jkb, Kna/Knb, Kpa/Kpb, M/N, S/s, Sda, Se, and Yta/Ytb, while some performed slightly worse: Fya/Fyb, K/k, Lua/Lub, and Vel ~99%–98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). Discussion: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.
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11.
  • Skotte, Line, et al. (författare)
  • Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
  • 2022
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
  • Tidskriftsartikel (refereegranskat)abstract
    • Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
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12.
  • Smedby, Karin Ekström, et al. (författare)
  • Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype
  • 2006
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 98:1, s. 51-60
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Some autoimmune and chronic inflammatory disorders are associated with increased risks of non-Hodgkin lymphoma (NHL). Because different NHL subtypes develop at different stages of lymphocyte differentiation, associations of autoimmune and inflammatory disorders with specific NHL subtypes could lead to a better understanding of lymphomagenic mechanisms. METHODS: In a population-based case-control study in Denmark and Sweden, 3055 NHL patients and 3187 matched control subjects were asked about their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. Logistic regression with adjustment for study matching factors was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for NHL overall and for NHL subtypes. RESULTS: Risks of all NHL were increased in association with rheumatoid arthritis (OR = 1.5, 95% CI = 1.1 to 1.9), primary Sjögren syndrome (OR = 6.1, 95% CI = 1.4 to 27), systemic lupus erythematosus (OR = 4.6, 95% CI = 1.0 to 22), and celiac disease (OR = 2.1, 95% CI = 1.0 to 4.8). All of these conditions were also associated with diffuse large B-cell lymphoma, and some were associated with marginal zone, lymphoplasmacytic, or T-cell lymphoma. Ever use of nonsteroidal anti-inflammatory drugs, systemic corticosteroids, and selected immunosuppressants was associated with risk of NHL in rheumatoid arthritis patients but not in subjects without rheumatoid arthritis. Also, multivariable adjustment for treatment had little impact on risk estimates. Psoriasis, sarcoidosis, and inflammatory bowel disorders were not associated with increased risk of NHL overall or of any NHL subtype. CONCLUSIONS: Our results confirm the associations between certain autoimmune disorders and risk of NHL and suggest that the associations may not be general but rather mediated through specific NHL subtypes. These NHL subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis.
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13.
  • Ullum, Henrik, et al. (författare)
  • Blood donation and blood donor mortality after adjustment for a healthy donor effect
  • 2015
  • Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 55:10, s. 2479-2485
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Studies have repeatedly demonstrated that blood donors experience lower mortality than the general population. While this may suggest a beneficial effect of blood donation, it may also reflect the selection of healthy persons into the donor population. To overcome this bias, we investigated the relation between blood donation frequency and mortality within a large cohort of blood donors. In addition, our analyses also took into consideration the effects of presumed health differences linked to donation behavior.STUDY DESIGN AND METHODS Using the Scandinavian Donation and Transfusion database (SCANDAT), we assessed the association between annual number of donations in 5-year windows and donor mortality by means of Poisson regression analysis. The analyses included adjustment for demographic characteristics and for an internal healthy donor effect, estimated among elderly donors exempted from continued donation because of age criteria.RESULTS Statistical analyses included 1,182,495 donors of whom 15,401 died during 9,526,627 person-years of follow-up. Analyses adjusted only for demographic characteristics showed a 18.6% reduction in mortality per additional annual donation (95% confidence interval [CI], 16.8%-20.4%). After additional adjustment for the internal healthy donor effect, each additional annual donation was associated with a 7.5% decreased mortality risk 7.5% (95% CI, 5.7%-9.4%).CONCLUSION We observed an inverse relationship between donation frequency and mortality. The magnitude of the association was reduced after adjustment for an estimate of self-selection in the donor population. Our observations indicate that repeated blood donation is not associated with premature death, but cannot be interpreted as conclusive evidence of a beneficial health effect.
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  • Akre, Olof, et al. (författare)
  • Maternal and gestational risk factors for hypospadias
  • 2008
  • Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:8, s. 1071-1076
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. METHODS: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) 4.6, 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > ;= 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6, 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6, 95% CI, 1.1-53). CONCLUSIONS: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.
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15.
  • Argirion, Ilona, et al. (författare)
  • Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies
  • 2023
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:5, s. 687-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL).Methods: Anti-EBV IgG and IgA antibody responses target-ing 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their associ-ation with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies repre-senting the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models.Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glyco-protein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types.Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis.Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.
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16.
  • Baecklund, Fredrik, et al. (författare)
  • A comprehensive evaluation of the role of genetic variation in follicular lymphoma survival
  • 2014
  • Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 15, s. 113-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survival in follicular lymphoma (FL) is highly variable, even within prognostic groups defined by tumor grade and the Follicular Lymphoma International Prognostic Index. Studies suggest that germline single nucleotide polymorphisms (SNPs) may hold prognostic information but further investigation is needed. Methods: We explored the association between SNPs and FL outcome using two approaches: 1) Two independent genome-wide association studies (GWAS) of similar to 300.000 SNPs followed by a meta-analysis encompassing 586 FL patients diagnosed in Denmark/Sweden 1999-2002 and in the United States 2001-2006; and 2) Investigation of 22 candidate-gene variants previously associated with FL outcome in the Danish/Swedish cohort (N = 373). We estimated time to lymphoma-specific death (approach 1 and 2) and lymphoma progression (approach 2) with hazard ratios (HR) and 95% confidence intervals (CI) in a multivariable Cox regression model. Results: In the GWAS meta-analysis, using a random effects model, no variants were associated with lymphoma-specific death at a genome-wide significant level (p < 5.0x10(-8)). The strongest association was observed for tightly linked SNPs on 17q24 near the ABCA10 and ABCA6 genes (rs10491178 HRrandom = 3.17, 95% CI 2.09-4.79, prandom = 5.24x10(-8)). The ABCA10 and ABCA6 genes belong to a family of genes encoding for ABC transporter proteins, implicated in multidrug resistance. In line with a previous study, rs2466571 in CD46 (HR = 0.73, 95% CI 0.58-0.91, p = 0.006) showed nominal association with lymphoma progression, as did two highly linked SNPs in IL8 (rs4073 HR = 0.78, 95% CI 0.62-0.97, p = 0.02; rs2227307 HR = 0.75, 95% CI 0.60-0.94, p = 0.01) previously associated with overall survival. Conclusions: The results suggest a possible role for multidrug resistance in FL survival and add to the evidence that genetic variation in CD46 and IL8 may have prognostic implications in FL. Our findings need further confirmation in other independent populations or in a larger multicenter GWAS.
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17.
  • Baecklund, Fredrik, et al. (författare)
  • Possible Interaction Between Cigarette Smoking and HLA-DRB1 Variation in the Risk of Follicular Lymphoma
  • 2017
  • Ingår i: American Journal of Epidemiology. - : OXFORD UNIV PRESS INC. - 0002-9262 .- 1476-6256. ; 185:8, s. 681-687
  • Tidskriftsartikel (refereegranskat)abstract
    • Follicular lymphoma (FL) risk is strongly associated with germline genetic variation in human leukocyte antigen (HLA) class II. Cigarette smoking has been suggested to increase FL risk, primarily among women. We hypothesized that amino acids in HLA-antigen D-related beta 1 subunit (DRB1) interact with smoking in FL risk, as shown for rheumatoid arthritis. We analyzed 373 patients with FL and 818 controls from 2 population-based case-control studies in Sweden and Denmark (1999-2003). Haplotypes in HLA-DRB1 were imputed at amino acid positions 11, 13, 28, 30, and 70-74 (shared epitope). We estimated the relative risk of FL as odds ratios with 95% confidence intervals for different smoking status/haplotype combinations. Interaction was defined as departure from additivity of effects and quantified by the attributable proportion (AP). Relative to never-smokers carrying no shared epitope alleles, smoking was associated with the risk of FL among all subjects (for former smokers, odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.10, 4.41; ORcurrent = 3.56, 95% CI: 1.60, 7.92) and women (ORformer = 2.95, 95% CI: 1.18, 7.37; ORcurrent = 5.63, 95% CI: 2.07, 15.3) carrying 2 shared epitope alleles but not among those carrying zero or 1 shared epitope allele. Smoking and shared epitope status interacted significantly as measured by AP (overall, AP = 0.6, 95% CI: 0.15, 1.0; for women, AP = 0.5, 95% CI: 0.005, 1.0). These results suggest a possible interaction between smoking and HLA-DRB1-associated antigen presentation in FL risk and provide a model to further unravel FL etiology.
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18.
  • Bernatsky, Sasha, et al. (författare)
  • Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
  • 2017
  • Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
  •  
19.
  • Berndt, Sonja, I, et al. (författare)
  • Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
  • 2022
  • Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
  • Tidskriftsartikel (refereegranskat)abstract
    • Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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20.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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21.
  • Berndt, Sonja I., et al. (författare)
  • Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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22.
  • Biggar, Robert J., et al. (författare)
  • Immunoglobulin subclass levels in patients with non-Hodgkin lymphoma
  • 2009
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:11, s. 2616-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Allergy/atopy has been suggested to protect against non-Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG(4) in 200 NHL patients and 200 age- and sex-matched controls. Patients with B-cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10-15% of B-cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG(4) and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B-cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B-cell NHL types. Low immunoglobulin levels appear to be a consequence of B-cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B-cell NHL.
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23.
  • Biggar, Robert J., et al. (författare)
  • Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma
  • 2008
  • Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 14:21, s. 6974-8
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially in nodular sclerosis Hodgkin lymphoma. EXPERIMENTAL DESIGN: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed by linear regression, adjusting for age and sex. RESULTS: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, P<0.0001). In pretreatment samples from pretreatment Hodgkin lymphoma patients (n=176), levels were correlated with more advanced stages (P(trend), 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms; however, levels were similar in nodular sclerosis and mixed cellularity subtypes, by EBV status, and in younger (<45 years old) and older patients. Patients tested soon after treatment onset had significantly lower levels than pretreatment patients; however, even >or=6 months after treatment onset, serum YKL-40 and IL-6 levels remained significantly increased compared with controls. In patients who died (n=12), pretreatment levels for YKL-40 and IL-6 were higher than in survivors, although not statistically significantly. CONCLUSIONS: Serum YKL-40 and IL-6 levels were increased in untreated Hodgkin lymphoma patients and those with more advanced stages but did not differ significantly by Hodgkin lymphoma histology. Following treatment, serum levels were significantly lower.
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24.
  • Cerhan, James R., et al. (författare)
  • Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1233-1238
  • Tidskriftsartikel (refereegranskat)abstract
    • Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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25.
  • Chang, Ellen T., et al. (författare)
  • Alcohol intake and risk of non-Hodgkin lymphoma in men and women
  • 2004
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 15:10, s. 1067-1076
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • OBJECTIVE: The effect of alcohol intake on risk of NHL is unclear. We therefore conducted a population-based case-control study to examine the association between alcohol and NHL risk. METHODS: 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2 years before the study. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between alcohol intake and NHL risk. RESULTS: Intake of total alcohol, beer, wine, or liquor was not associated with risk of overall NHL. There was no difference in risk of NHL among those who habitually consumed above 19.1 g of ethanol per day, compared to those who consumed on average 0-2.2 g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); Ptrend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); Ptrend = 0.06). Total alcohol, beer, wine, or liquor intake was not associated with any major histopathologic subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia. CONCLUSIONS: Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.
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26.
  • Chang, Ellen T., et al. (författare)
  • Body mass index and risk of malignant lymphoma in Scandinavian men and women
  • 2005
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:3, s. 210-218
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The incidence of non-Hodgkin lymphoma and prevalence of obesity are increasing globally. A suggested positive association between obesity and risk of non-Hodgkin lymphoma has prompted us to investigate the relationship between body mass index (BMI) and risk of malignant lymphoma subtypes in a population-based case-control study. METHODS: Telephone interviews were conducted with 3055 case patients with non-Hodgkin lymphoma and 618 case patients with Hodgkin lymphoma diagnosed between October 1, 1999, and August 30, 2002, and 3187 population-based control subjects. The interviews assessed current height, normal adult weight, and other possible risk factors. Multivariable odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for risk of lymphoma were estimated by unconditional logistic regression. All statistical tests were two-sided. RESULTS: BMI was not associated with risk of overall non-Hodgkin lymphoma or of Hodgkin lymphoma (for example, comparing the highly obese group [BMI > or =35.0 kg/m2] with the normal-weight group [BMI = 18.5-24.9 kg/m2], OR for risk of non-Hodgkin lymphoma = 0.9, 95% CI = 0.6 to 1.3; P(trend) across all categories of BMI = .27). BMI was also not associated with risk of any non-Hodgkin lymphoma subtype evaluated, although there was some evidence of a positive association with risk of diffuse large B-cell lymphoma (for example, comparing the highly obese group with the normal-weight group, OR for diffuse large B-cell lymphoma = 1.5, 95% CI = 0.9 to 2.4; P(trend) =.05). CONCLUSIONS: Excess weight does not appear to be associated with an increased risk of malignant lymphoma in general, or with a risk of most major lymphoma subtypes. Hence, the growing incidence of obesity is unlikely to be an important contributor to the increasing incidence of non-Hodgkin lymphoma worldwide.
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27.
  • Chang, Ellen T., et al. (författare)
  • Dietary factors and risk of non-hodgkin lymphoma in men and women
  • 2005
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 14:2, s. 512-20
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased worldwide in recent decades. Diet could influence NHL risk by modulating the immune system, although evidence is limited. We did a population-based case-control study to determine whether differences in diet were associated with NHL risk. METHODS: A total of 597 NHL cases and 467 population controls in Sweden completed a semiquantitative food frequency questionnaire evaluating their dietary habits 2 years before the interview. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (95% CI) for associations between food intake and risk of NHL. RESULTS: High consumption of dairy products and fried red meat was associated with increased risk of NHL. The OR of NHL for individuals in the highest quartile compared with the lowest quartile of dairy intake was 1.5 (95% CI, 1.1-2.2; P(trend) = 0.003). The OR for the highest versus lowest quartile of fried red meat intake was 1.5 (95% CI, 1.0-2.1; P(trend) = 0.02). In contrast, high consumption of fruits and vegetables was associated with reduced risk of NHL, particularly follicular lymphoma, among women but not men. Compared with the lowest quartile of vegetable intake, the OR of follicular lymphoma among women in the highest quartile of vegetable intake was 0.3 (95% CI, 0.1-0.7; P(trend) = 0.002). CONCLUSIONS: The positive associations of NHL risk with dairy products and fried red meat and the inverse association with fruits and vegetables suggest that diet affects NHL risk and could explain the increase of some histopathogic subtypes.
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28.
  • Chang, Ellen T., et al. (författare)
  • Family history of hematopoietic malignancy and risk of lymphoma
  • 2005
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 97:19, s. 1466-1474
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • BACKGROUND: A family history of hematopoietic malignancy is associated with an increased risk of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), although the magnitude of the relative risk is unclear. We estimated the association between familial hematopoietic cancer and risk of lymphoma using validated, registry-based family data, and we also investigated whether associations between some environmental exposures and risk of lymphoma vary between individuals with and without such a family history. METHODS: In a population-based case-control study of malignant lymphoma, 1506 case patients and 1229 control subjects were linked to the Swedish Multi-Generation Register and then to the Swedish Cancer Register to ascertain history of cancer in first-degree relatives of patients with malignant lymphoma. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with the risk of lymphoma. RESULTS: A history of hematopoietic malignancy in any first-degree relative was associated with an increased risk of all NHL (OR = 1.8, 95% CI = 1.2 to 2.5), common B-cell NHL subtypes, and HL. Relative risks were generally stronger in association with sibling hematopoietic cancer (OR for all NHL = 3.2, 95% CI = 1.3 to 7.6) than with parental hematopoietic cancer (OR = 1.6, 95% CI = 1.1 to 2.3). A family history of NHL or chronic lymphocytic leukemia (CLL) was associated with an increased risk of several NHL subtypes and HL, whereas familial multiple myeloma was associated with a higher risk of follicular lymphoma. There was no statistically significant heterogeneity in NHL risk associations with environmental factors between individuals with and without familial hematopoietic malignancy. CONCLUSIONS: The increased risk of NHL and HL among individuals with a family history of hematopoietic malignancy was approximately twofold for both lymphoma types. There was no evidence that etiologic associations varied between familial NHL and nonfamilial NHL.
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29.
  • Chang, Ellen T., et al. (författare)
  • Medication use and risk of non-Hodgkin's lymphoma
  • 2005
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 162:10, s. 965-974
  • Tidskriftsartikel (refereegranskat)abstract
    • Conflicting results from previous epidemiologic studies shed little light on whether medication use is associated with risk of non-Hodgkin's lymphoma (NHL). To investigate this question, the authors conducted a population-based case-control study in Denmark and Sweden from 1999 to 2002, including 3,055 incident NHL cases and 3,187 controls. Participants reported their past use of medications and history of particular medical conditions. Unconditional logistic regression was used to estimate multivariate odds ratios and 95% confidence intervals for the associations between medication use and risk of NHL; all statistical tests were two sided. Use of antibiotics more than 10 times during adulthood was positively associated with risk of NHL and most major NHL subtypes; when users were compared with nonusers, the odds ratio for NHL was 1.8 (95% confidence interval: 1.4, 2.3); p(trend) for total antibiotic use <0.001. In addition, high cumulative use of nonsteroidal anti-inflammatory drugs was marginally associated with elevated NHL risk. Other medications evaluated were not associated with risk of NHL or its most common subtypes. Findings suggest that inflammation, infections, susceptibility to infections, and/or use of antibiotics or nonsteroidal anti-inflammatory drugs to treat these conditions may increase the risk of NHL. However, most of the medications examined were not associated with NHL risk.
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30.
  • Chang, Ellen T., et al. (författare)
  • Reliability of self-reported family history of cancer in a large case-control study of lymphoma
  • 2006
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 98:1, s. 61-68
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Case-control studies of familial cancer risk traditionally rely on self-reported family history of cancer, which may bias results due to differential recall between case patients and control subjects. To evaluate the reliability of self-reported data, we analyzed questionnaire and registry-based data on familial cancer from a population-based case-control study of malignant lymphoma. METHODS: All 1508 lymphoma case patients and 1229 control subjects completed a telephone interview assessing cancer in family members. Participants were linked to the Swedish Multi-Generation Register and Cancer Register to identify confirmed cancer diagnoses in first-degree relatives. The sensitivity and specificity of self-reported familial cancer were calculated among case patients and control subjects and were compared using logistic regression. All statistical tests were two-sided. RESULTS: Lymphoma case patients reported a family history of any cancer with statistically significantly higher sensitivity than control subjects (0.85, 95% confidence interval [CI] = 0.83 to 0.87 and 0.80, 95% CI = 0.77 to 0.82, respectively) but with marginally lower specificity (0.89, 95% CI = 0.87 to 0.91 and 0.92, 95% CI = 0.90 to 0.94, respectively). The sensitivity of self-reporting familial cancers by site ranged from less than 0.20 for rare malignancies to nearly 0.75 for more common types, whereas specificity was generally 0.98 or greater. For most sites, the reliability of self-report was similar in patients and control subjects. However, patients reported familial hematopoietic cancer with statistically significantly higher sensitivity (0.60, 95% CI = 0.57 to 0.62) than control subjects (0.38, 95% CI = 0.35 to 0.40). Odds ratios for the association between familial cancer and risk of non-Hodgkin lymphoma were consistently higher when based on self-reported, compared with registry data-based, family history of any cancer or of hematopoietic cancer. CONCLUSIONS: Reliability of self-reported family history of cancer varies between case patients and control subjects. Recall bias may thus produce biased results in case-control studies of familial cancer risk.
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31.
  • Conde, Lucia, et al. (författare)
  • Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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32.
  • Delahaye-Sourdeix, Manon, et al. (författare)
  • A Novel Risk Locus at 6p21.3 for Epstein-Barr Virus-Positive Hodgkin Lymphoma
  • 2015
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:12, s. 1838-1843
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A proportion of the genetic variants involved in susceptibility to Hodgkin lymphoma differ by the tumor's Epstein-Barr virus (EBV) status, particularly within the MHC region.METHODS: We have conducted an SNP imputation study of the MHC region, considering tumor EBV status in 1,200 classical Hodgkin lymphoma (cHL) cases and 5,726 control subjects of European origin. Notable findings were genotyped in an independent study population of 468 cHL cases and 551 controls.RESULTS: We identified and subsequently replicated a novel association between a common genetic variant rs6457715 and cHL. Although strongly associated with EBV-positive cHL [OR, 2.33; 95% confidence interval (CI), 1.83-2.97; P = 7 × 10(-12)], there was little evidence for association between rs6457715 and the EBV-negative subgroup of cHL (OR, 1.06; 95% CI, 0.92-1.21), indicating that this association was specific to the EBV-positive subgroup (Phet < P = 10(-8)). Furthermore, the association was limited to EBV-positive cHL subgroups within mixed cell (MCHL) and nodular sclerosis subtypes (NSHL), suggesting that the association is independent of histologic subtype of cHL.CONCLUSIONS: rs6457715, located near the HLA-DPB1 gene, is associated with EBV-positive cHL and suggests this region as a novel susceptibility locus for cHL.IMPACT: This expands the number of genetic variants that are associated with cHL and provides additional evidence for a critical and specific role of EBV in the etiology of this disease. Cancer Epidemiol Biomarkers Prev; 24(12); 1838-43.
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33.
  • Din, Lennox, et al. (författare)
  • Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
  • 2019
  • Ingår i: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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34.
  • Edgren, Gustaf, et al. (författare)
  • Improving health profile of blood donors as a consequence of transfusion safety efforts
  • 2007
  • Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 47:11, s. 2017-2024
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transfusion safety rests heavily on the health of blood donors. Although they are perceived as being healthier than average, little is known about their long-term disease patterns and to which extent the blood banks' continuous efforts to optimize donor selection has resulted in improvements. Mortality and cancer incidence among blood donors in Sweden and Denmark was investigated. Study Design and Methods: All computerized blood bank databases were compiled into one database, which was linked to national population and health data registers. With a retrospective cohort study design, 1,110,329 blood donors were followed for up to 35 years from first computer-registered blood donation to death, emigration, or December 31, 2002. Standardized mortality and incidence ratios expressed relative risk of death and cancer comparing blood donors to the general population. Results: Blood donors had an overall mortality 30 percent lower (99% confidence interval [CI] 29%-31%) and cancer incidence 4 percent lower (99% CI 2%-5%) than the background population. Mortality rates and cancer incidence were lowest for outcomes that are recognized as being related to lifestyle factors such as smoking or to the selection criteria for blood donation. Blood donors recruited in more recent years exhibited a lower relative mortality than those who started earlier. Conclusion: Blood donors enjoy better than average health. Explicit and informal requirements for blood donation in Scandinavia, although mostly of a simple nature, have successfully refined the selection of a particularly healthy subpopulation.
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35.
  • Ekström Smedby, Karin, et al. (författare)
  • Childhood social environment and risk of non-Hodgkin lymphoma in adults
  • 2007
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:22, s. 11074-11082
  • Tidskriftsartikel (refereegranskat)abstract
    • Better hygiene and sanitation and decreasing family size parallel the increasing incidence of non-Hodgkin lymphoma (NHL) in many populations around the world. However, whether sibship size, birth order, and crowding are related to adult NHL risk is not clear. We investigated how family structure and childhood social environment were related to the risk of NHL and NHL subtypes in a large Scandinavian population-based case control study with 6,242 participants aged 18 to 74 years. Detailed exposure information was obtained through telephone interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression, and all statistical tests were two-sided. Having four or more siblings was associated with a moderately increased risk of NHL, compared with having no siblings (OR 1.34, 95% CI 1.11-1.62, P(trend) < 0.001). Having four or more older siblings was associated with a similar risk increase (OR 1.33, 95% CI 1.12-1.59, P(trend) = 0.003) compared with being the oldest, whereas number of younger siblings was unrelated overall. The associations were independent of other environmental exposures and did not vary by country, age, or sex. High household crowding was also positively associated with risk of NHL. Results were slightly stronger for diffuse large B-cell and T-cell lymphomas than for other major NHL subtypes. Our findings add to the evidence that large sibship size, late birth order, and childhood crowding are associated with an elevated risk of NHL. Effect mechanisms may be related to early age at onset and high frequency of specific infections or total microbial exposure in childhood.
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36.
  • Enciso-Mora, Victor, et al. (författare)
  • A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1126-1130
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.
  •  
37.
  • Foo, Jia Nee, et al. (författare)
  • Coding Variants at Hexa-allelic Amino Acid 13 of HLA-DRB1 Explain Independent SNP Associations with Follicular Lymphoma Risk
  • 2013
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 93:1, s. 167-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 x 10(-15)). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 x 10(-14)). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.
  •  
38.
  • Gholiha, Alex Reza, et al. (författare)
  • Checkpoint CD47 expression in classical Hodgkin lymphoma
  • 2022
  • Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 197:5, s. 580-589
  • Tidskriftsartikel (refereegranskat)abstract
    • The glycoprotein CD47 regulates antiphagocytic activity via signal regulatory protein alpha (SIRPa). This study investigated CD47 expression on Hodgkin and Reed–Sternberg (HRS) cells in the classical Hodgkin lymphoma (cHL) tumour microenvironment and its correlation with prognosis, programmed-death (PD) immune markers, and SIRPa+ leukocytes. We conducted immunohistochemistry with CD47 and SIRPa antibodies on diagnostic biopsies (tissue microarrays) from cHL patients from two cohorts (n = 178). In cohort I (n = 136) patients with high expression of CD47 on HRS cells (n = 48) had a significantly inferior event-free survival [hazard ratio (HR) = 5.57; 95% confidence interval (CI), 2.78–11.20; p < 0.001] and overall survival (OS) (HR = 8.54; 95% CI, 3.19–22.90; p < 0.001) compared with patients with low expression (n = 88). The survival results remained statistically significant in multivariable Cox regression adjusted for known prognostic factors. In cohort II (n = 42) high HRS cell CD47 expression also carried shorter event-free survival (EFS) (HR = 5.96; 95% CI, 1.20–29.59; p = 0.029) and OS (HR = 5.61; 95% CI, 0.58–54.15; p = 0.136), although it did not retain statistical significance in the multivariable analysis. Further, high CD47 expression did not correlate with SIRPa+ leukocytes or PD-1, PD-L1 and PD-L2 expression. This study provides a deeper understanding of the role of CD47 in cHL during an era of emerging CD47 therapies.
  •  
39.
  • Gholiha, Alex R., et al. (författare)
  • High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B-symptoms
  • 2019
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 184:2, s. 192-201
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti-CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell-infiltration was associated with the presence of B-symptoms (P = 0·028) and advanced stage, IIB-IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event-free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour-associated plasma cells in cHL reflect an important component in the microenvironment of cHL.
  •  
40.
  • Gholiha, Alex R., et al. (författare)
  • Revisiting IL-6 expression in the tumor microenvironment of classical Hodgkin lymphoma
  • 2021
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:6, s. 1671-1681
  • Tidskriftsartikel (refereegranskat)abstract
    • Interleukin-6 (IL-6) can induce therapeutic resistance for several cancer agents currently used to treat classical Hodgkin lymphoma (cHL). We aimed to investigate whether the presence of IL-6(+) leukocytes and IL-6(+) Hodgkin-Reed-Sternberg (HRS) cells in the tumor microenvironment (TME) was associated with adverse survival outcomes, expression of other immune markers, and serum IL-6 levels. We used a contemporarily treated cohort (n = 136), with a median follow-up of 13.8 years (range, 0.59-15.9 years). We performed immunohistochemistry with an IL-6 antibody on tissue microarrays from diagnostic biopsies of cHL patients. Patients with IL-6(+) leukocytes >= 1% (n = 54 of 136) had inferior event-free survival (hazard ratio [HR] = 3.58; 95% confidence interval [CI], 1.80-7.15) and overall survival (HR = 6.71; 95% CI, 2.51-17.99). The adverse survival was maintained in multivariate Cox regression and propensity score-matched analyses, adjusting for well-known poor-prognostic covariates. The presence of IL-6(+) HRS cells and high serum IL-6 levels were not associated with survival. IL-6(+) leukocytes correlated with increased proportions of IL-6(+) HRS cells (P < .01), CD138(+) plasma cells (P < .01), CD68(+) macrophages (P = .02), and tryptase-positive mast cells (P < .01). IL-6(+) HRS cells correlated with increased proportions of CD68+ macrophages (P = .03), programmed death-ligand 1-positive (PD-L1(+)) leukocytes (P = .04), and PD-L1(+) HRS cells (P < .01). Serum-IL-6 lacked correlation with IL-6 expression in the TME. This is the first study highlighting the adverse prognostic impact of IL-6(+) leukocytes in the TME in a cohort of contemporarily treated adult patients with cHL.
  •  
41.
  • Glimelius, Ingrid, 1975-, et al. (författare)
  • Predictors of histology, tissue eosinophilia and mast cell infiltration in Hodgkin's Lymphoma : a population-based study
  • 2011
  • Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 87:3, s. 208-216
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:  Classical Hodgkin’s lymphoma (HL) lesions comprise few tumour cells, surrounded by numerous inflammatory cells. Like in other malignancies, the microenvironment is presumed to be clinically important in HL; however, microenvironment predictors remain poorly characterised. The aim of this study was to investigate how selected patient characteristics and genetic factors affect HL phenotype, in particular tissue eosinophilia, mast cell counts and HL histological subtype.Methods:  In a population-based study, patients with HL were interviewed about potential HL risk factors. Available tumours, n = 448, were classified histologically; the number of eosinophils and mast cells were estimated, and eosinophil cationic protein (ECP) and eosinophil protein-x (EPX) gene polymorphisms were determined. Associations were assessed in regression models.Results:  Self-reported history of asthma was predictive of having tumour eosinophilia [≥200 eosinophils/10 high power fields, univariate odds ratio (OR) = 2.22, 95% CI 1.06–4.64, P = 0.03]. High numbers of eosinophils were predominantly seen in patients carrying the genotype ECP434GG [multivariate relative levels (RLs) = 1.84, 95% CI 1.02–3.30, P = 0.04]. Lower number of eosinophils was seen in Epstein–Barr virus (EBV)-positive tumours (univariate RL = 0.52, 95% CI 0.3–0.9, P = 0.02) and in older patients (univariate RL = 0.85, 95% CI 0.73–0.99, P = 0.03). Well-known factors such as young age, female sex and EBV-negative status predicted nodular sclerosis histology.Conclusion:  The number of eosinophils in HL tumours is influenced by patient traits such as asthma, ECP genotype and EBV status. EBV status was predictive of histology.
  •  
42.
  • Grau, Katrine, et al. (författare)
  • No association between frequent apheresis donation and risk of fractures : a retrospective cohort analysis from Sweden
  • 2017
  • Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 57:2, s. 390-396
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Citrate anticoagulation during apheresis induces transient alterations in calcium homeostasis. It is unknown whether the repeated, transient alterations in calcium homeostasis experienced by repeated apheresis donors affects bone turnover to increase fracture risk. Our aim was to investigate the risk of osteoporotic and nonosteoporotic fracture among voluntary, frequent apheresis donors. STUDY DESIGN AND METHODS: All apheresis donors were identified from the Scandinavian Donations and Transfusions database (SCANDAT2), which includes information on over 1.6 million blood donors from Sweden and Denmark from the years 1968 and 1981, respectively. Only data from Sweden were used for these analyses. Information on fractures was obtained by linking SCANDAT2 to hospital registers. Poisson regression was used to compute incidence rate ratios of fractures in relation to the cumulative number of apheresis donations, both overall and in fixed time windows. RESULTS: In total, 140,289 apheresis donors (67,970 women and 72,319 men) were identified from the SCANDAT2 database and were followed for up to 23 years. We observed no association between the frequency of apheresis donation and the risk of fracture either in the overall study period or during fixed-length time windows. The incidence rate ratio of fractures in donors who had made 100 or more cumulative apheresis donations was 0.99(95% confidence interval, 0.92-1.06) compared with donors who had made from 9 to 24 donations. The results were similar in analyses stratified by sex and restricted to postmenopausal women. CONCLUSIONS: The absence of an association between repeated apheresis donation and fracture risk indicates that apheresis collection is safe with regard to bone health.
  •  
43.
  • Gunnarsson, Rebeqa, et al. (författare)
  • Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia
  • 2011
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 96:8, s. 1161-1169
  • Tidskriftsartikel (refereegranskat)abstract
    • Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
  •  
44.
  • Gunnarsson, Rebeqa, et al. (författare)
  • Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia-A comparative study of four differently designed, high resolution microarray platforms
  • 2008
  • Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 93, s. 0536-0536
  • Tidskriftsartikel (refereegranskat)abstract
    • Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.
  •  
45.
  • Halmin, Märit, et al. (författare)
  • Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion : A Binational Cohort Study
  • 2017
  • Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 166:4, s. 248-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists.Objective: To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects.Design: Binational cohort study.Setting: All transfusion recipients in Sweden and Denmark. Patients: 854 862 adult patients who received transfusions from 2003 to 2012.Measurements: Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression.Results: Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was -0.2% (95% CI, -0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units.Limitation: Observational study; risk of confounding by indication.Conclusion: Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed.
  •  
46.
  • Hjalgrim, Henrik, et al. (författare)
  • Cigarette smoking and risk of Hodgkin lymphoma : a population-based case-control study
  • 2007
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 16:8, s. 1561-1566
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies have inconsistently reported an association between tobacco smoking and Hodgkin lymphoma (HL) risk. The conflicting finding may reflect etiologic heterogeneity between HL subtypes, warranting further characterization of the relationship. METHODS: We collected information on tobacco-smoking habits in 586 classic HL cases and 3,187 population controls in a Danish-Swedish case-control study. HL EBV status was established for 499 cases by standard techniques. Odds ratios (OR) for an association with cigarette smoking were calculated by logistic regression for HL overall and stratified by age, sex, major histology subtypes, and tumor EBV status, adjusting for known confounders. RESULTS: Compared with never smokers, current cigarette smokers were at an increased overall HL risk [adjusted OR, 1.57; 95% confidence interval (95% CI), 1.22-2.03]. The association was strongest for EBV-positive HL (adjusted OR, 2.36; 95% CI, 1.51-3.71), but also applied to EBV-negative HL (adjusted OR, 1.43; 95% CI, 1.05-1.97; P(homogeneity EBV-pos) versus P(homogeneity EBV-neg) = 0.04). The association did not vary appreciably by age, sex, or histologic subtype, the apparent EBV-related difference present in all strata. There was no evidence of a dose-response pattern, whether by age at smoking initiation, daily cigarette consumption, number of years smoking, or cumulative number of cigarettes smoked. Similar results were obtained in analyses using non-HL patients (n = 3,055) participating in the founding study as comparison group. CONCLUSION: The observed association between cigarette smoking and HL risk is consistent with previous findings and biologically credible. Although not easily dismissed as an artifact, the limited evidence of a dose-response pattern renders the overall evidence of causality weak.
  •  
47.
  • Hjalgrim, Henrik, et al. (författare)
  • HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma
  • 2010
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:14, s. 6400-6405
  • Tidskriftsartikel (refereegranskat)abstract
    • A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60-2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV-related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV-related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL.
  •  
48.
  • Hjalgrim, Henrik, et al. (författare)
  • Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma
  • 2007
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 67:5, s. 2382-2388
  • Tidskriftsartikel (refereegranskat)abstract
    • Infectious mononucleosis (IM) has been associated with an increased risk of Hodgkin lymphoma (HL), implicating a role for Epstein-Barr virus (EBV) in HL development. Although essential to the understanding of the association, it has remained uncertain if the relationship is restricted to the EBV-positive subset of HL. We collected information on mononucleosis history and childhood socioenvironmental characteristics in a population-based study of 586 patients with classic HL and 3,187 controls in Denmark and Sweden. Tumor EBV status was established for 499 cases by immunohistochemistry and in situ hybridization techniques. Odds ratios (OR) for the relationship between HL risk and mononucleosis and other risk factors were estimated by logistic regression for HL in younger (18-44 years) and older (45-74 years) adults, overall and by tumor EBV status. All analyses were adjusted for country-specific measures of maternal education and mononucleosis history. IM was associated with an increased risk of EBV-positive [OR, 3.23; 95% confidence interval (95% CI) 1.89-5.55] but not EBV-negative HL (OR, 1.35; 95% CI, 0.86-2.14). Risk of EBV-positive HL varied with time since IM and was particularly pronounced in younger adults (OR, 3.96; 95% CI, 2.19-7.18). IM-associated lymphomas occurred with a median of 2.9 years (1.8-4.9 years) after infection. The EBV specificity of the IM association was corroborated by a case-case comparison of IM history between younger adult EBV-positive and EBV-negative HL patients (OR(IM EBV+ HL versus EBV- HL), 2.68; 95% CI, 1.40-5.12). We found further evidence that IM is associated only with EBV-positive HL. This finding is compatible with the notion that EBV-positive and EBV-negative HL may have different etiologies.
  •  
49.
  • Hjalgrim, Henrik, et al. (författare)
  • Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin's lymphoma
  • 2000
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 85:5, s. 639-642
  • Tidskriftsartikel (refereegranskat)abstract
    • According to recent results, patients with non-melanoma skin cancers are at increased risk of developing non-Hodgkin's lymphoma (NHL). The prognostic significance of this association is unknown. Two cohorts of patients with a first diagnosis of non-melanoma skin cancer and a subsequent diagnosis of either NHL (n = 170) or colon cancer (n = 435) were established using national cancer registry data in Denmark. Two other cohorts of patients in whom NHL (n = 600) or colon cancer (n = 1,541) was the patients' first known malignancy served as comparison groups. Mortality rates were compared using Cox's regression analysis. Among patients younger than 80 years at NHL diagnosis, a history of non-melanoma skin cancer was associated with significantly increased mortality [relative risk (RR) = 1.54; 95% confidence interval: 1.19-1.99]. This association was present in both men (RR = 1.38; 1.02-1.86) and women (RR = 2.15; 1.31-3.54) and was similar after both major subtypes of non-melanoma skin cancer. Overall, antedating non-melanoma skin cancer had no prognostic significance for colon cancer patients (RR = 1.00; 0.84-1.18). Whatever the underlying mechanism, our observation has potential clinical implications. If substantiated in other settings, NHL patients with prior non-melanoma skin cancer may constitute a subgroup of lymphoma patients in need of particular therapeutic attention.
  •  
50.
  • Hollander, Peter, et al. (författare)
  • An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome
  • 2018
  • Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 100:1, s. 88-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows anongoing inflammatory response consisting of varying degrees of infiltrating eosinophils,mast cells, macrophages, regulatory T lymphocytes (Tregs), and activated lymphocytes surrounding the malignant cells. Herein, different immune signatures are characterized and correlated with treatment outcome.Methods: Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL) and overall survival were analyzed using Cox proportional hazards regression.Results: The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95% confidence interval 1.05-3-15). Epstein-Barrvirus (EBV)-positive cases had higher proportions of macrophages and activated lymphocytes than EBV negative, but neither of those leukocytes predicted prognosis.Conclusions: Abundant Tregs (anergic signature) indicate a shorter TTP, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.
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