| 1. |
- Andersson, Ulrika, et al.
(author)
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A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
- 2010
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 12, s. 17-17
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Journal article (peer-reviewed)abstract
- Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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| 2. |
- Ding, Yuan C, et al.
(author)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Journal article (peer-reviewed)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 3. |
- Haghighi, Mona, et al.
(author)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 4. |
- Ivarsson, Tord, 1946, et al.
(author)
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Remission and Relapse Across Three Years in Pediatric Obsessive-Compulsive Disorder Following Evidence-Based Treatments
- 2024
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - 0890-8567 .- 1527-5418. ; 63:5, s. 519-527
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Journal article (peer-reviewed)abstract
- Objective: To examine relapse rates following remission in a 3-year follow-up study in pediatric patients with obsessive-compulsive disorder (OCD) treated with cognitive–behavioral therapy (CBT) in a first step, and either continued CBT or sertraline (randomized selection) in a second step. Method: Participants (N = 269) fulfilled DSM-IV OCD criteria with a mean severity on the Children's Yale–Brown Obsessive Compulsive Scale (CY-BOCS) of 24.6 (SD = 5.1) and were included in analyses according to intent-to-treat principles. CBT used manualized exposure and response prevention (ERP) during both steps 1 and 2, and step 2 sertraline medication used flexible dosing. The follow-up schedules were timed to 6, 12, 24, and 36 months following step 1 CBT. Remission was defined as a CY-BOCS score ≤10 and relapse as an elevated CY-BOCS score ≥16 in those who had remitted. Results: A good third of our patients were in stable and full remission at all examinations (n = 98, 36.4%). Further, some in remission following treatment (n = 36, 13.4%) had mild OCD at some examinations. Relapses during follow-up were not uncommon (n = 28, 10.4%), but in many patients these improved again (n = 10, 3.7%) and were in remission at the final 3-year follow-up. Furthermore, a considerable proportion (n = 50, 18.6%) of the patients were initial non-remitters to the treatment but achieved remission at some point during the follow-up. In addition, 11.5% (n = 31) had persistent OCD but reached remission by the last follow-up. Finally, a smaller segment of our sample (9.7%, n = 26), did not attain remission at any point during the study. Conclusion: Our outcome paints a more promising picture of pediatric OCD long-term outcome than previous studies have done. However, both relapse rates and the presence of initial non-remitters and persistent OCD show that treatments need improvement, particularly for those who respond slowly, partially, or not at all. The lack of a general psychiatric interview at follow-up is a marked limitation. Clinical trial registration information: Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study; https://www.isrctn.com; ISRCTN66385119
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| 5. |
- Jacobs, Kevin B, et al.
(author)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 6. |
- Jensen, Sanne, et al.
(author)
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The Children's Yale-Brown Obsessive-Compulsive Scale's auxiliary items: Long-term outcome
- 2020
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In: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier BV. - 2211-3649 .- 2211-3657. ; 27
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Journal article (peer-reviewed)abstract
- © 2020 Elsevier Inc. Objective: Standard assessment of pediatric obsessive-compulsive disorder (OCD) patients includes ratings of insight, avoidance, indecisiveness, sense of responsibility, pervasive slowness, pathological doubting, and obsession-free intervals. The present study aims to identify pre-treatment associations of these clinical features to symptom severity and symptom dimensions as well as to describe and analyze the long-term levels and distribution in different treatment responder groups. Method: Severity ratings as well as clinical feature ratings were evaluated in 268 pediatric OCD patients using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) at seven time points before, during, and up to three years after first-line cognitive-behavioral therapy. The CY-BOCS auxiliary items were evaluated on the basis of three symptom severity trajectory classes: acute, slow, and limited responders. Results: Insight, avoidance, pervasive slowness, and obsession-free intervals were positively associated with pre-treatment symptom severity. Symptom dimensions were associated with different auxiliary items. At three-year follow-up, the limited responder class had higher scores than the acute and slow responder classes on all items except for responsibility. Conclusion: The CY-BOCS auxiliary items are closely related to symptom dimensions and partly to symptom severity. The features appear to be dynamic concepts prone to change, yet, less so in patients showing limited long-term treatment response.
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| 7. |
- Kragh, Kristin, et al.
(author)
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Convergent and divergent validity of the schedule for affective disorders and schizophrenia for school-age children - present and lifetime version diagnoses in a sample of children and adolescents with obsessive-compulsive disorder.
- 2019
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In: Nordic journal of psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 73:2, s. 111-117
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Journal article (peer-reviewed)abstract
- The presence of comorbid conditions associated with paediatric obsessive-compulsive disorder (OCD) is reported to range from 50 to 80% and to have an impact on treatment outcome. Accurate identification of comorbid psychiatric disorders is necessary in order to provide personalised care. Reliable and valid diagnostic interviews are essential in the process of establishing the correct diagnoses. The objective of this study was to evaluate the convergent and divergent validity of four diagnose categories generated by the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). The diagnose categories were: anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). The K-SADS-PL was applied in a clinical sample of youth aged 7-17 years (N=269), who were participants in the Nordic long-term OCD-treatment study (NordLOTS). Youth and parents completed measures to evaluate symptoms of anxiety, depression, ADHD, and ODD. Convergent and divergent validity of K-SADS-PL anxiety diagnosis was supported based on both anxiety self- and parent-reports. Similarly, support was found for convergent and divergent validity of ADHD and ODD diagnoses. For depressive disorder, support for convergent validity was found based on the depression self-report. Support for divergent validity of depression was found based on both the depression self- and parent-reports. Results of the present study suggest that the K-SADS-PL generates valid diagnoses of comorbid anxiety disorders, depression disorders, ODD, and ADHD in children and adolescents with OCD.
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| 8. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 9. |
- McCarthy, Bridget J, et al.
(author)
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Risk factors for oligodendroglial tumors : A pooled international study
- 2011
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In: Neuro-Oncology. - Charlottesville, VA : Carden Jennings Pub.. - 1522-8517 .- 1523-5866. ; 13:2, s. 242-250
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Journal article (peer-reviewed)abstract
- Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
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| 10. |
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