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- Björkegren, Karin, et al.
(författare)
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General symptom reporting in female fibromyalgia patients and referents : a population-based case-referent study
- 2009
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 9, s. 402-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fibromyalgia is characterized by widespread musculoskeletal pain and palpation tenderness. In addition to these classic symptoms, fibromyalgia patients tend to report a number of other complaints. What these other complaints are and how often they are reported as compared with related referents from the general population is not very well known. We therefore hypothesized that subjects with fibromyalgia report more of a wide range of symptoms as compared with referents of the same sex and age from the general population. METHODS: 138 women with diagnosed fibromyalgia in primary health care and 401 referents from the general population matched to the cases by sex, age and residential area responded to a postal questionnaire where information on marital status, education, occupational status, income level, immigrant status, smoking habits physical activity, height and weight history and the prevalence of 42 defined symptoms was sought. RESULTS: The cases had lower educational and income levels, were more often unemployed, on sick leave or on disability pension and were more often first generation immigrants than the referents. They were also heavier, shorter and more often had a history of excessive food intake and excessive weight loss. When these differences were taken into account, cases reported not only significantly more presumed fibromyalgia symptoms but also significantly more of general symptoms than the referents. The distribution of symptoms was similar in subjects with fibromyalgia and referents, indicating a generally higher symptom reporting level among the former. CONCLUSION: Subjects with fibromyalgia had a high prevalence of reported general symptoms than referents. Some of these differences may be a consequence of the disorder while others may reflect etiological processes.
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| 2. |
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| 3. |
- Catucci, Irene, et al.
(författare)
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Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility
- 2018
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600. ; 20:4, s. 452-457
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Tidskriftsartikel (refereegranskat)abstract
- PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations.MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes.ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene.ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.Genetics in Medicine advance online publication, 24 August 2017; doi:10.1038/gim.2017.123.
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| 4. |
- Ofverholm, Ingegerd, et al.
(författare)
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Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
- 2024
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research (AACR). - 1078-0432 .- 1557-3265. ; 30:12, s. 2647-2658
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tumor classification is a key component in personalized cancer care. For soft-tissue and bone tumors, this classification is currently based primarily on morphology assessment and IHC staining. However, these standard-of-care methods can pose challenges for pathologists. We therefore assessed how whole-genome and whole-transcriptome sequencing (WGTS) impacted tumor classification and clinical management when interpreted together with histomorphology.Experimental Design: We prospectively evaluated WGTS in routine diagnostics of 200 soft-tissue and bone tumors suspicious for malignancy, including DNA and RNA isolation from the tumor, and DNA isolation from a peripheral blood sample or any non-tumor tissue.Results: On the basis of specific genomic alterations or absence of presumed findings, WGTS resulted in reclassification of 7% (13/197) of the histopathologic diagnoses. Four cases were downgraded from low-grade sarcomas to benign lesions, and two cases were reclassified as metastatic malignant melanomas. Fusion genes associated with specific tumor entities were found in 30 samples. For malignant soft-tissue and bone tumors, we identified treatment relevant variants in 15% of cases. Germline pathogenic variants associated with a hereditary cancer syndrome were found in 22 participants (11%).Conclusions: WGTS provides an important dimension of data that aids in the classification of soft-tissue and bone tumors, correcting a significant fraction of clinical diagnoses, and identifies molecular targets relevant for precision medicine. However, genetic findings need to be evaluated in their morphopathologic context, just as germline findings need to be evaluated in the context of patient phenotype and family history.
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| 5. |
- Wallander, Karin
(författare)
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Hereditary predisposition and prognostic prediction in cancer
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is a genetic disease. The cancer cells evolve clonally through changes of their genome, gaining malignant characteristics. In hereditary cancer syndromes, a genetic aberration which puts the cells one step closer to being malignant is inherited and present throughout whole body. Not all genes associated with hereditary cancer syndromes have been discovered, and the spectrum of cancers connected to each cancer-associated gene is not yet known. When it is feasible, the genetic changes within the tumour can be analysed by performing a tissue biopsy. Alternatively, analysis of cell-free DNA from a blood sample might give the same information. Cell-free DNA is released into the blood stream from both malignant and nonmalignant cells, and it carries the same genetic aberrations as the cells it comes from. The aims of this thesis were to improve oncogenetic counselling, by increasing the knowledge about who should be offered genetic tests and what genes to test, and to improve treatment decision-making, by developing a clinical pipeline for a new cancer biomarker, cell-free tumour DNA. In Study I, we explored the genetic cause for a suspected highly penetrant, autosomal dominant rectal cancer syndrome in one family. We analysed the blood samples from six family members by massive parallel sequencing, and found six variants that could contribute to the increased risk for rectal cancer in the family. The variants were in the genes CENPB, ZBTB20, CLINK, LRRC26, TRPM1, and NPEPL1. None of the variants have a known connection to hereditary cancer syndromes and further studies are needed to investigate their potential involvement. In Study II, we evaluated the efficacy of performing massive parallel sequencing in patients with three or more primary tumours. We found two likely pathogenic variants in two individuals. In a woman with a clinical diagnosis of MEN1, we found a synonymous variant in the MEN1 gene. By RNA analysis, we could show that the variant activates a cryptic splice site, which leads to a deletion of 14 nucleotides, and a frameshift in the RNA transcript. The variant segregated with disease in the family, and it was classified as likely disease-causing. In a woman with multiple Lynch-associated tumours and microsatellite instability, we found a synonymous variant in the MLH1 gene. This variant has recently been described as an epimutation, leading to methylation of the MLH1 promoter, and Lynch syndrome. Both these genes had previously been analysed in blood samples from the two women, but the variants had not been recognized as pathogenic. We therefore conclude that genetic re-analysis may be beneficial, especially for patients with a clear clinical diagnosis of a specific hereditary cancer syndrome. In Study III, we developed a clinical method for detecting cancer-associated CNAs (copy number alterations) in cell-free tumour DNA from patients with gastro-oesophageal cancer. The same clinical laboratory protocol as for non-invasive prenatal testing at Karolinska University Hospital, Stockholm, was used, and for the last bioinformatic steps WISECONDOR and ichorCNA were used. This generated a list of potentially cancerassociated CNAs, which we manually annotated. We compared the variants to the tissue sample from the same participant, and also with a control set of samples from pregnant women. We found cancer-associated CNAs in 14/26 (54%) of the individuals with detectable cancer-associated CNAs in the tissue samples. Potentially clinically actionable amplifications were detected in the genes VEGFA, EGFR, and FGFR2. This study showed that the clinical pipeline we have set up for the non-invasive prenatal testing workflow can be used in the oncogenetic field, and CNA analysis in patients with gastro-oesophageal cancer might be used as a biomarker in the future. In conclusion, we report six new genes with a potential involvement in a hereditary rectal cancer syndrome, we suggest re-analysis might be beneficial for patients without a molecular diagnosis but who fulfil testing criteria for specific cancer syndromes, and we show that the non-invasive prenatal testing clinical pipeline can also be used in the oncogenetic setting.
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| 6. |
- Wallander, Karin, et al.
(författare)
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Sensitive Detection of Cell-Free Tumour DNA Using Optimised Targeted Sequencing Can Predict Prognosis in Gastro-Oesophageal Cancer
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:4, s. 1160-
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Cancer in the stomach and oesophagus is deadly when discovered at a late stage. There are no good biomarkers for its detection or for making a prognostic prediction. In this study, we evaluate the analysis of cell-free DNA as a prognostic cancer biomarker. Cell-free DNA is DNA released from any tissue to a body fluid. When there is a tumour in the body, some of the cell-free DNA will come from that tumour, and it can be detected in a blood sample. We show that the detection of cell-free DNA from the cancer correlates to a worse prognosis than when no tumour DNA is detected. We also show that the method of analysis is important. Either a tissue biopsy must be included as a validation of the genetic variants detected or analysis of the blood cells or another blood sample after tumour resection needs to be analysed to improve detection. In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients.
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| 7. |
- Wallander, Lisa, 1975-
(författare)
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Measuring Professional Judgements : An Application of the Factorial Survey Approach to the Field of Social Work
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The focus of this thesis is the factorial survey approach as a method for studying professional judgements in social work. The factorial survey approach, which was first introduced in the social sciences around the beginning of the 1980s, constitutes an advanced method for measuring human judgements of social objects. At the general level, this quasi-experimental approach involves presenting respondents with fictive descriptions of social objects (vignettes), in which selected characteristics describing the objects to be judged are simultaneously manipulated. This thesis consists of four studies: In Study I, I explore the general use of the factorial survey approach in sociology between 1982 and 2006. Study II and Study III consist of factorial survey applications in the field of professional judgement in Swedish substance misuse treatment, as organized by the social services. To be more specific, the aims of these papers are to disentangle predictors of social work practitioners’ choices of inpatient or outpatient substance misuse treatment (Study II), and of social work practitioners’ judgements about eligibility for compulsory care (Study III). Finally, in Study IV, I present a conceptual and an analytical framework for the application of the factorial survey approach to the study of professional judgements in social work.
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