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  • 201. Cloughesy, Tim
    et al.
    Wick, Wolfgang
    Mason, Warren
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
    Saran, Frank
    Nishikawa, Ryo
    Carpentier, Antoine F.
    Hoang-Xuan, Khe
    Kavan, Petr
    Cernea, Dana
    Brandes, Alba A.
    Revil, Cedric
    Abrey, Lauren
    Chinot, Olivier L.
    Survival analysis of patients with a PFS event who did not receive post-progression therapy in AVAglio (bevacizumab [BEV] plus radiotherapy [RT] and temozolomide [TMZ] for newly diagnosed glioblastoma [GBM])2014In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 16, no 5Article in journal (Other academic)
  • 202. Costas, Laura
    et al.
    Lujan-Barroso, Leila
    Benavente, Yolanda
    Allen, Naomi E.
    Amiano, Pilar
    Ardanaz, Eva
    Besson, Caroline
    Boeing, Heiner
    Bueno-de-Mesquita, Bas
    Cervenka, Iris
    Fortner, Renee T.
    Fournier, Agnes
    Gunter, Marc
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Maria Huerta, Jose
    Jerkeman, Mats
    Jirstrom, Karin
    Kaaks, Rudolf
    Karakatsani, Anna
    Khaw, Kay-Tee
    Kotanidou, Anastasia
    Lund, Eiliv
    Masala, Giovanna
    Mattiello, Amalia
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Menendez, Virginia
    Murphy, Neil
    Nieters, Alexandra
    Overvad, Kim
    Riboli, Elio
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schmidt, Julie A.
    Sieri, Sabina
    Tjonneland, Anne
    Trichopoulou, Antonia
    Tumino, Rosario
    Vermeulen, Roel
    Weiderpass, Elisabete
    de Sanjose, Silvia
    Agudo, Antonio
    Casabonne, Delphine
    Reproductive Factors, Exogenous Hormone Use, and Risk of B-Cell Non-Hodgkin Lymphoma in a Cohort of Women From the European Prospective Investigation Into Cancer and Nutrition2019In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, no 2, p. 274-281Article in journal (Refereed)
    Abstract [en]

    The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.

  • 203.
    Crnalic, Sead
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Löfvenberg, Richard
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Early diagnosis and treatment is crucial for neurological recovery after surgery for metastatic spinal cord compression in prostate cancer2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 809-815Article in journal (Refereed)
    Abstract [en]

    Background. Spinal cord compression is an oncological and surgical emergency. Delays in referral and diagnosis may influence functional outcome. It is therefore important to identify patients who will regain or maintain ability to walk after surgery. The aim of the present study was to examine current practice for referral and diagnosis of prostate cancer patients with spinal cord compression and to identify prognostic factors for neurological outcome after surgery.

    Patients and methods. The study includes 68 consecutive patients with prostate cancer who underwent surgery due to neurological compromise.  Intervals from onset of neurological symptoms to referral, diagnosis, and treatment were analyzed in relation to functional outcome. The prognostic significance of preoperative clinical parameters on gait function one month after surgery was evaluated.

    Results. Patients who were referred from local hospitals had longer delay to surgery than those who directly presented to the cancer centre (p=0.004). The rate of diagnosis with MRI increased through the week and peaked on Friday, with few patients being diagnosed during weekends. Ability to walk before surgery, hormone-naive prostate cancer, and/or shorter time from loss of ambulation were associated with more favorable neurological outcome. In patients with hormone-refractory disease who were unable to walk before surgery regaining of ambulation was associated with: duration of paresis <48 hours (p=0.005), good preoperative performance status (p=0.04), preoperative PSA serum level <200 ng/ml (p=0.03), and surgery with posterior decompression and stabilization (p=0.03).

    Conclusion. Early diagnosis and rapid treatment of spinal cord compression in prostate cancer patients is crucial for neurological recovery. Rising of awareness for the condition among patients at risk and among physicians is mandatory as well as improvement of local and regional guidelines for treatment.

  • 204.
    Crnalic, Sead
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löfvenberg, Richard
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Outcome after surgery for metastatic spinal cord compression in 54 patients with prostate cancer2012In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 1, p. 80-86Article in journal (Refereed)
    Abstract [en]

    Background and purpose The criteria for selecting patients who may benefit from surgery of spinal cord compression in metastatic prostate cancer are poorly defined. We therefore studied patients operated for metastatic spinal cord compression in order to evaluate outcome of surgery and to find predictors of survival. Patients and methods We reviewed the records of 54 consecutive patients with metastatic prostate cancer who were operated for spinal cord compression at Umeå University Hospital. The indication for surgery was neurological deficit due to spinal cord compression. 41 patients had hormone-refractory cancer and 13 patients had previously untreated, hormone-naïve prostate cancer. 29 patients were operated with posterior decompression only, and in 25 patients posterior decompression and stabilization was performed. Results Preoperatively, 6/54 of patients were able to walk. 1 month after surgery, 33 patients were walking, 15 were non-ambulatory, and 6 had died. Mortality rate was 11% at 1 month, 41% at 6 months, and 59% at 1 year. In the hormone-naïve group, 8/13 patients were still alive with a median postoperative follow-up of 26 months. In the hormone-refractory group, median survival was 5 months. Patients with hormone-refractory disease and Karnofsky performance status (KPS) of ≤ 60% had median survival of 2.5 months, whereas those with KPS of 70% and KPS of ≥ 80% had a median survival of 7 months and 18 months, respectively (p < 0.001). Visceral metastases were present in 12/41 patients with hormone-refractory tumor at the time of spinal surgery, and their median survival was 4 months-as compared to 10 months in patients without visceral metastases (p = 0.003). Complications within 30 days of surgery occurred in 19/54 patients. Interpretation Our results indicate that patients with hormone-naive disease, and those with hormone-refractory disease with good performance status and lacking visceral metastases, may be helped by surgery for metastatic spinal cord compression.

  • 205.
    Crnalic, Sead
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hörnberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lerner, Ulf H
    Umeå University, Faculty of Medicine, Department of Odontology.
    Tieva, Åse
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients2010In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 17, no 4, p. 885-895Article in journal (Refereed)
    Abstract [en]

    Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.

  • 206.
    Crnalic, Sead
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Löfvenberg, Richard
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Predicting survival for surgery of metastatic spinal cord compression in prostate cancer: a new score2012In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 37, no 26, p. 2168-2176Article in journal (Other academic)
    Abstract [en]

    Study design. We retrospectively analyzed prognostic factors for survival in prostate cancer patients operated for metastatic spinal cord compression.

    Objective. The aim was to obtain a clinical score for prediction of survival after surgery.

    Summary of background data. Survival prognosis is important when deciding about treatment of patients with metastatic spinal cord compression. The criteria for identifying prostate cancer patients who may benefit from surgical treatment are unclear.

    Patients and methods The study comprised 68 consecutive patients with prostate cancer operated for metastatic spinal cord compression at Umeå University Hospital, Sweden. The indication for surgery was neurological deficit; 53 patients had hormone-refractory prostate cancer, and 15 patients had previously untreated, hormone-naïve prostate cancer. In 42 patients posterior decompression was performed and 26 patients were operated with posterior decompression and stabilization.

    Results A new score for prediction of survival was developed based on the results of survival analyses. The score includes: hormone status of prostate cancer, Karnofsky performance status, evidence of visceral metastasis, and preoperative serum PSA. The total scores ranged from 0 to 6. Three prognostic groups were formulated: group A (n = 32) with scores 0-1; group B (n = 23) with scores 2-4, and group C (n = 12) with scores 5-6. The median overall survival was 3 (0.3 - 20) months in group A, 16 (1.8 - 59) months in group B, and in group C more than half (7 of 12) of patients were still alive.

    Conclusion We present a new prognostic score for predicting survival of prostate cancer patients after surgery for metastatic spinal cord compression. The score is easy to apply in clinical practice and may be used as additional support when making decision about treatment.

  • 207. Cruz Alsina, Fernando
    et al.
    Javier Hita, Francisco
    Aldana Fontanet, Paula
    Irala, Dolores
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ledda, Fernanda
    Paratcha, Gustavo
    Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling2016In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 17, no 4, p. 601-616Article in journal (Refereed)
    Abstract [en]

    Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development.

  • 208. Cui, Baoxia
    et al.
    Zheng, Biying
    Zhang, Xi
    Stendahl, Ulf
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Sonia
    Wallin, Keng-Ling
    Mutation of PIK3CA: possible risk factor for cervical carcinogenesis in older women2009In: International Journal of Oncology, ISSN 1019-6439, Vol. 34, no 2, p. 409-416Article in journal (Refereed)
    Abstract [en]

    PIK3CA encodes the p110alpha catalytic subunit of PI 3-kinase, which regulates signaling pathways important for neoplasia, cell proliferation and apoptosis. Somatic mutations in this gene have been detected in several solid human tumors. We investigated these mutations in cervical carcinoma and its precursors, and their association with HPV infection and patient clinical data. The mutations were analyzed using post-PCR direct genomic DNA sequencing. Samples included 9 cervical cancer cell lines, 184 invasive cervical carcinomas, and 30 cervical neoplasias. Missense mutations of PIK3CA were identified in 15/184 (8.15%) invasive cervical carcinomas. One novel mutation G1638C (Q546H) was found. Three mutations were identified in the cervical cancer lines. No mutations were found in the precursors. The difference in mutation frequency between invasive and pre-invasive lesions was not significant (p=0.1372). In relation to age and HPV, the mutation rate was significantly higher in patients>or=60 years (p=0.001), while the rate of HPV infection was higher in patients

  • 209. Cust, Anne E
    et al.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lukanova, Annekatrin
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Kaaks, Rudolf
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis: a prospective study.2009In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 113, no 3, p. 567-576Article in journal (Refereed)
    Abstract [en]

    It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case–control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II–IV (P heterogeneity all <0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30–0.78, P trend = 0.004); leptin, 0.64 (95% CI, 0.41–1.00, P trend = 0.06); and HbA1c, 0.47 (95% CI, 0.28–0.80, P trend = 0.005). For stage II–IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression.

  • 210.
    Dahlin, Anna M.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hollegaard, Mads V.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hougaard, David M.
    Deltour, Isabelle
    Hjalmars, Ulf
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma2015In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 125, no 1, p. 75-78Article in journal (Refereed)
    Abstract [en]

    Recent studies have described a number of genes that are frequently altered in medulloblastoma tumors and that have putative key roles in the development of the disease. We hypothesized that common germline genetic variations in these genes may be associated with medulloblastoma development. Based on recent publications, we selected 10 genes that were frequently altered in medulloblastoma: CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot samples) from 243 childhood medulloblastoma cases and 247 control subjects from Sweden and Denmark. Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P (combined) < 0.05). The findings were however not statistically significant following correction for multiple testing by the very stringent Bonferroni method. The results do not support our hypothesis that common germline genetic variants in the ten studied genes are associated with the risk of developing medulloblastoma.

  • 211.
    Dahlin, Anna M.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hougaard, David M.
    Bybjerg-Grauholm, Jonas
    Deltour, Isabelle
    Hultman, Christina M.
    Kähler, Anna K.
    Karlsson, Robert
    Hjalmars, Ulf
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults: A Case-Control Study2019In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 7, p. 1252-1258Article in journal (Refereed)
    Abstract [en]

    Background: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA.

    Methods: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation.

    Results: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09–1.35; P = 5.8 × 10−4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10−5).

    Conclusions: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts.

    Impact: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.

  • 212.
    Dahlin, Anna M.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ghasimi, Soma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Relation between Established Glioma Risk Variants and DNA Methylation in the Tumor2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0163067Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies and candidate gene studies have identified several genetic variants that increase glioma risk. The majority of these variants are non-coding and the mechanisms behind the increased risk in carriers are not known. In this study, we hypothesize that some of the established glioma risk variants induce aberrant DNA methylation in the developing tumor, either locally (gene-specific) or globally (genome-wide). In a pilot data set including 77 glioma patients, we used Illumina beadchip technology to analyze genetic variants in blood and DNA methylation in matched tumor samples. To validate our findings, we used data from the Cancer Genome Atlas, including 401 glioblastoma patients. Consensus clustering identified the glioma CpG island methylator phenotype (gCIMP) and two additional subgroups with distinct patterns of global DNA methylation. In the pilot dataset, gCIMP was associated with two genetic variants in CDKN2B-AS1, rs1412829 and rs4977756 (9p21.3, p = 8.1 x 10(-7) and 4.8 x 10(-5), respectively). The association was in the same direction in the TCGA dataset, although statistically significant only when combining individuals with AG and GG genotypes. We also investigated the relation between glioma risk variants and DNA methylation in the promoter region of genes located within 30 kb of each variant. One association in the pilot dataset, between the TERT risk variant rs2736100 and lower methylation of cg23827991 (in TERT; p = 0.001), was confirmed in the TCGA dataset (p = 0.001). In conclusion, we found an association between rs1412829 and rs4977756 (9p21.3, CDKN2B-AS1) and global DNA methylation pattern in glioma, for which a trend was seen also in the TCGA glioblastoma dataset. We also found an association between rs2736100 (in TERT) and levels of methylation at cg23827991 (localized in the same gene, 3.3 kbp downstream of the risk variant), which was validated in the TCGA dataset. Except for this one association, we did not find strong evidence for gene-specific DNA methylation mediated by glioma risk variants.

  • 213. Dahlrot, R. H.
    et al.
    Dowsett, J.
    Fosmark, S.
    Malmstrom, A.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm Gotland Stockholm Sweden.
    Boldt, H.
    de Stricker, K.
    Sorensen, M. D.
    Poulsen, H. S.
    Lysiak, M.
    Soderkvist, P.
    Rosell, J.
    Hansen, S.
    Kristensen, B. W.
    Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis2018In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, no 2, p. 172-184Article in journal (Refereed)
    Abstract [en]

    Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status.

    Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population‐based Region of Southern Denmark (RSD)‐cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM‐patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules.

    Results: When divided at the median, patients with low expression of MGMT protein (AF‐low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS‐cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF‐low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF‐low had the best outcome; median OS 23.1 and 20.0 months, respectively.

    Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour‐specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

  • 214.
    Dahmoun, Marju
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Apoptosis, proliferation, and sex steroid receptors in endometrium and endometrial carcinoma2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on the involvement of apoptosis and proliferation in the mechanisms of menstruation and hormonal replacement therapy, HRT, as well as in the mechanisms of progesterone therapy in endometrial carcinoma.

    The aim of the first study was to investigate endometrium for 4 days before and for 2 days during menstruation. In the epithelium, rapid increase in the apoptotic index, decreasing expression of estrogen receptor α (ER) and progesterone receptor (PR), and minimal proliferation were observed prior to menstruation. In the stroma, an increase in the expression of ER and PR and proliferation was seen before the final decrease, and increased apoptosis was seen during menstruation. Thus, apoptosis is involved in the remodeling of the endometrium during menstruation.

    Postmenopausal endometrium showed unaffected homeostasis, i.e. unchanged ratio between apoptotic index and Ki-67 index during substitution therapy. ER expression was decreased both in the epithelium and stroma, while PR showed some increase in receptor expression. The unchanged homeostasis contributes to endometrial safety during combined continuous HRT.

    Unchanged apoptosis and increasing proliferation were observed with increasing tumor grade in 29 patients with endometrioid endometrial carcinoma, which may contribute to greater aggression as tumor grade increases. Decreased proliferation was observed after medroxy-progesterone at 20 mg per day particularly in the foci of maximal proliferation in G1 and G2 tumors. The expression of ER was unchanged, while PR was decreased in the foci of maximal expression for PR in G1 and G2 tumors. Since high proliferation and PR expression also coexisted in the same foci, evaluated in G1 and G2 tumors, the effect of progesterone could be facilitated in these tumor groups. High expression of sex steroid receptors was also a predicting factor for good response to progesterone (= decrease in proliferation), while the amount of stroma could not predict that effect.

  • 215.
    Dahmoun, Marju
    et al.
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology.
    Boman, Karin
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Cajander, S
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology.
    Intratumoral effects of medroxy-progesterone on proliferation, apoptosis, and sex steroid receptors in endometrioid endometrial adenocarcinoma2004In: Gynecol Oncol, ISSN 0090-8258, Vol. 92, no 1, p. 116-126Article in journal (Refereed)
  • 216.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lung cancer in males: an epidemiological study in northern Sweden with special regard to smoking and occupation1986Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In a case-control study comprising 589 cases of male lung cancer in northern Sweden longitudinal data concerning occupations, employments and smoking habits were collected by questionnaires.

    Pipe smoking was as common as cigarette smoking and gave very similar relative risk. The pipe smoking cases, however, had significantly higher mean age and mean smoking years at the time of diagnosis than the cigarette smoking cases. In ex- smokers, the relative risk gradually decreased from 5 years after smoking cessation but this decrease was much less pronounced in ex-pipe smokers than in ex-cigarette smokers. High relative risks were obtained for small cell and squamous cell carcinomas. For adenocarcinoma the relative risk was considerably lower but still significantly increased. The population etiologic fraction attributable to smoking was about 80% in this series.

    Some occupational groups (underground miners, copper smelter workers, electricians and plumbers) exposed to previously known lung carcinogenic agents had considerably increased odds ratios, which persisted after adjustment for smoking. A slightly elevated odds ratio was observed in a group of blue collar workers potentially exposed to lung carcinogenic agents but this elevation generally disappeared after adjustment for smoking. For two specific subgroups, asphalt and concrete workers and pulp workers, the overrisk persisted after adjustment for smoking. Farmers and foresters had strikingly low odds ratios, which could only partly be explained by their more moderate smoking habits. The population etiologic fraction attributable to occupation was in the reported material assessed to 9 per cent.

    Professional drivers had higher average tobacco consumption than non-drivers, which explained the slightly increased crude odds ratio found for the occupational group as a whole. Smoking drivers in an upper age group (70 and over), however, had a high relative risk of lung cancer, while in a lower age group (under 70) no significant increase was found. The results in the older age group suggested a multiplicative effect between smoking and the occupational exposure.

    The study clearly verified the increased lung cancer risk in underground miners. An obvious dose-response relation was found with high risk after long time exposure. All analyses concerning underground miners suggested an interaction of a multiplicative type between underground mining and smoking in the causation of lung cancer. The cases of small cell carcinoma among the underground miners had shorter average latency time and in contrast to the other part of the material, shorter average age than the cases with epidermoid cancer.

  • 217. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Anderson, Harald
    Holte, Harald Jr.
    Osterborg, Anders
    Merup, Mats
    Brown, Peter de Nully
    Kuittinen, Outi
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole
    Sundstrom, Christer
    Delabie, Jan
    Rafkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle
    High-dose chemotherapy and autologuos stem cell transplantation in previously untreated peripheral T-Cell Lymphoma: Final analysis of a large prospective multicenter study (NLG-T-01)2011In: 53rd ASH Annual Meeting and Exposition: Session: 731. Clinical Allogeneic and Autologous Transplantation - Results: Myeloma, Lymphomas and Multiple Sclerosis ; Monday, December 12, 2011: 7:00 AM Douglas Pavilion C (Manchester Grand Hyatt San Diego), washington, USA: American Society of Hematology , 2011, Vol. 118, no 21, p. 155-156Conference paper (Refereed)
  • 218. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Anderson, Harald
    Holte, Harald
    Osterborg, Anders
    Merup, Mats
    Brown, Peter
    Kuittinen, Outi
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole V.
    Sundstrom, Christer
    Delabie, Jan
    Ralfkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle E.
    Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-012012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 25, p. 3093-3099Article in journal (Refereed)
    Abstract [en]

    Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL. J Clin Oncol 30: 3093-3099. (C) 2012 by American Society of Clinical Oncology

  • 219.
    Danell, Rickard
    et al.
    Umeå University, Faculty of Social Sciences, Sociology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Kan forskning ha stordriftsfördelar?2008In: Onkologi i Sverige, no 2, p. 32-40Article in journal (Refereed)
  • 220.
    Dasu, Alexandru
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Toma-Dasu, Iuliana
    Franzen, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    The risk of secondary cancers in patients treated for prostate carcinoma: an analysis with competition dose response model2009In: IFMBE Proceedings, Berlin: Springer , 2009, p. 237-240Conference paper (Refereed)
    Abstract [en]

    The risk for radiation-induced cancers has become increasingly important as patient survival following radiotherapy has increased due to the advent of new methods for early detection and advanced treatment. Attempts have been made to quantify the risk of cancer that may be associated with various treatment approaches, but the accuracy of predictions is rather low due to the influence of many confouding factors. It is the aim of this paper to investigate the impact of dose heterogeneity and inter-patient anatomical heterogeneity that may be encountered in a population of patients undergoing radiotheray and are thought to influence risk predictions. Dose volume histograms from patients treated with radiation for the carcinoma of the prostate have been used to calculate the risk for secondary malignancies using a competition dose-response model previously developed. Biologically-relevant parameters derived from clinical and experimental data have been used for the model. The results suggested that dose heterogeneity plays an important role in predicting the risk for secondary cancer and that it should be taken into account throught the use of dose volume histograms. Consequently, dose-response relationships derived for uniform relationships should be used with care to predict the risk for secondary malignancies in heterogeneously irradiated tissues. Inter-patient differences could lead to considerable uncertainties in the shape of the relationship between predicted risk and average tissue dose, as seen in epidemiological studies. They also lead to rather weak correlations between the risk for secondary malignancies and target volumes. The results stress the importance of taking into account the details of the clinical delivery of dose in radiotherapy plan evaluation or for retrospective analyses of the induction of secondary cancers. Nevertheless, the levels of risks are generally low and they could be regarded as teh price of success for the advances in the radiotherapy of the prostate.

  • 221.
    Dasu, Alexandru
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Toma-Dasu, Iuliana
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    The risk for secondary cancers in patients treated for prostate carcinoma: an analysis with completion dose response model2009In: IFMBE Proceedings of the World Congress on Medical Physics and Biomedical Engineering, September 7 - 12, 2009, Munich, Germany / [ed] Olaf Dössel, Wolfgang C. Schlegel, Springer Verlag , 2009, p. 237-240Conference paper (Refereed)
    Abstract [en]

    The risk for radiation-induced cancers has become increasingly important as patient survival following radiotherapy has increased due to the advent of new methods for early detection and advanced treatment. Attempts have been made to quantify the risk of cancer that may be associated with various treatment approaches, but the accuracy of predictions is rather low due to the influence of many confounding factors. It is the aim of this paper to investigate the impact of dose heterogeneity and inter-patient anatomical heterogeneity that may be encountered in a population of patients undergoing radiotherapy and are thought to influence risk predictions. Dose volume histograms from patients treated with radiation for the carcinoma of the prostate have been used to calculate the risk for secondary malignancies using a competition dose-response model previously developed. Biologically-relevant parameters derived from clinical and experimental data have been used for the model. The results suggested that dose heterogeneity plays an important role in predicting the risk for secondary cancer and that it should be taken into account through the use of dose volume histograms. Consequently, dose-response relationships derived for uniform relationships should be used with care to predict the risk for secondary malignancies in heterogeneously irradiated tissues. Inter-patient differences could lead to considerable uncertainties in the shape of the relationship between predicted risk and average tissue dose, as seen in epidemiological studies. They also lead to rather weak correlations between the risk for secondary malignancies and target volumes. The results stress the importance of taking into account the details of the clinical delivery of dose in radiotherapy for treatment plan evaluation or for retrospective analyses of the induction of secondary cancers. Nevertheless, the levels of risks are generally low and they could be regarded as the price of success for the advances in the radiotherapy of the prostate.

  • 222.
    Dasu, Alexandru
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Toma-Dasu, Iuliana
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia2003In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 48, no 17, p. 2829-2842Article in journal (Refereed)
    Abstract [en]

    The tumour microenvironment is considered to be responsible for the outcome of cancer treatment and therefore it is extremely important to characterize and quantify it. Unfortunately, most of the experimental techniques available now are invasive and generally it is not known how this influences the results. Non-invasive methods on the other hand have a geometrical resolution that is not always suited for the modelling of the tumour response. Theoretical simulation of the microenvironment may be an alternative method that can provide quantitative data for accurately describing tumour tissues.

    This paper presents a computerized model that allows the simulation of the tumour oxygenation. The model simulates numerically the fundamental physical processes of oxygen diffusion and consumption in a two-dimensional geometry in order to study the influence of the different parameters describing the tissue geometry. The paper also presents a novel method to simulate the effects of diffusion-limited (chronic) hypoxia and perfusion-limited (acute) hypoxia.

    The results show that all the parameters describing tissue vasculature are important for describing tissue oxygenation. Assuming that vascular structure is described by a distribution of inter-vessel distances, both the average and the width of the distribution are needed in order to fully characterize the tissue oxygenation. Incomplete data, such as distributions measured in a non-representative region of the tissue, may not give relevant tissue oxygenation.

    Theoretical modelling of tumour oxygenation also allows the separation between acutely and chronically hypoxic cells, a distinction that cannot always be seen with other methods. It was observed that the fraction of acutely hypoxic cells depends not only on the fraction of collapsed blood vessels at any particular moment, but also on the distribution of vessels in space as well.

    All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations.

  • 223. Davis, Faith G
    et al.
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Aldape, Ken
    Barnholtz-Sloan, Jill S
    Bondy, Melissa L
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bruner, Janet M
    Burger, Peter C
    Collins, V Peter
    Inskip, Peter D
    Kruchko, Carol
    McCarthy, Bridget J
    McLendon, Roger E
    Sadetzki, Siegal
    Tihan, Tarik
    Wrensch, Margaret R
    Buffler, Patricia A
    Issues of diagnostic review in brain tumor studies: from the brain tumor epidemiology consortium2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 3, p. 484-489Article in journal (Refereed)
    Abstract [en]

    Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices differ. A meeting of neuropathologists and epidemiologists focused on brain tumor classification issues in the context of protocol needs for consortial studies (http://epi.grants.cancer.gov/btec/). It resulted in recommendations relevant to brain tumors and possibly other rare disease studies. Two categories of brain tumors have enough general agreement over time, across regions, and between individual pathologists that one can consider using existing diagnostic data without further review: glioblastomas and meningiomas (as long as uniform guidelines such as those provided by the WHO are used). Prospective studies of these tumors benefit from collection of pathology reports, at a minimum recording the pathology department and classification system used in the diagnosis. Other brain tumors, such as oligodendroglioma, are less distinct and require careful histopathologic review for consistent classification across study centers. Epidemiologic study protocols must consider the study specific aims, diagnostic changes that have taken place over time, and other issues unique to the type(s) of tumor being studied. As diagnostic changes are being made rapidly, there are no readily available answers on disease classification issues. It is essential that epidemiologists and neuropathologists collaborate to develop appropriate study designs and protocols for specific hypothesis and populations.

  • 224. Davis, Faith
    et al.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Grutsch, James
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Second primary tumors following a diagnosis of meningioma in Sweden, 1958-1997.2007In: Neuroepidemiology, ISSN 1423-0208, Vol. 29, no 1-2, p. 101-106Article in journal (Refereed)
  • 225.
    Daşu, Alexandru
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Toma-Daşu, Iuliana
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Secondary malignancies from prostate cancer radiation treatment: a risk analysis of the influence of target margins and fractionation patterns2011In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 79, no 3, p. 738-746Article in journal (Refereed)
    Abstract [en]

    The results have shown the complex interplay between the risk for secondary malignancies, the details of the treatment delivery, and the patient heterogeneity that may influence comparisons between the long-term effects of various treatment techniques. Nevertheless, absolute risk levels seem very small and comparable to mortality risks from surgical interventions, thus supporting the robustness of radiation therapy as a successful treatment modality for prostate carcinomas.

  • 226.
    de Jong, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Adherence to adjuvant endocrine therapy after breast cancer in Sweden - With focus on regional differences and review of the material.2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 227. Del Campo, J M
    et al.
    Roszak, A
    Bidzinski, M
    Ciuleanu, T E
    Hogberg, T
    Wojtukiewicz, M Z
    Poveda, A
    Boman, Karin
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Westermann, A M
    Lebedinsky, C
    Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer.2009In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, ISSN 1569-8041, Vol. 20, no 11, p. 1794-802Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC). PATIENTS AND METHODS: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. RESULTS: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). CONCLUSIONS: Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

  • 228. Dewi, Nikmah Utami
    et al.
    Boshuizen, Hendriek C.
    Johansson, Mattias
    Vineis, Paolo
    Kampman, Ellen
    Steffen, Annika
    Tjonneland, Anne
    Halkjaer, Jytte
    Overvad, Kim
    Severi, Gianluca
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Li, Kuanrong
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Klinaki, Eleni
    Tumino, Rosario
    Palli, Domenico
    Mattiello, Amalia
    Tagliabue, Giovanna
    Peeters, Petra H.
    Vermeulen, Roel
    Weiderpass, Elisabete
    Gram, Inger Torhild
    Maria Huerta, Jose
    Agudo, Antonio
    Sanchez, Maria-Jose
    Ardanaz, Eva
    Dorronsoro, Miren
    Ramon Quiros, Jose
    Sonestedt, Emily
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Key, Tim
    Khaw, Kay-Tee
    Wareham, Nick
    Cross, Amanda J.
    Norat, Teresa
    Riboli, Elio
    Fanidi, Anouar
    Muller, David
    Bueno-de-Mesquita, H. Bas
    Anthropometry and the Risk of Lung Cancer in EPIC2016In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 184, no 2, p. 129-139Article in journal (Refereed)
    Abstract [en]

    The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.

  • 229. Dik, Vincent K
    et al.
    Bueno-de-Mesquita, H Bas
    Van Oijen, Martijn GH
    Siersema, Peter D
    Uiterwaal, Cuno SPM
    Van Gils, Carla H
    Van Duijnhoven, Fränzel JB
    Cauchi, Stéphane
    Yengo, Loic
    Froguel, Philippe
    Overvad, Kim
    Bech, Bodil H
    Tjønneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Fagherazzi, Guy
    Kühn, Tilman
    Campa, Daniele
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Peppa, Eleni
    Oikonomou, Eleni
    Palli, Domenico
    Grioni, Sara
    Vineis, Paolo
    Tumino, Rosaria
    Panico, Salvatore
    Peeters, Petra HM
    Weiderpass, Elisabete
    Engeset, Dagrun
    Braaten, Tonje
    Dorronsoro, Miren
    Chirlaque, María-Dolores
    Sánchez, María-José
    Barricarte, Aurelio
    Zamora-Ros, Raul
    Argüelles, Marcial
    Jirström, Karin
    Wallström, Peter
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Arctic Research Centre at Umeå University.
    Travis, Ruth C
    Khaw, Kay-Tee
    Wareham, Nick
    Freisling, Heinz
    Licaj, Idlir
    Jenab, Mazda
    Gunter, Marc J
    Murphy, Neil
    Romaguera-Bosch, Dora
    Riboli, Elio
    Coffee and tea consumption, genotype based CYP1A2 and NAT2 activity, and colorectal cancer risk: results from the EPIC cohort study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 2, p. 401-412Article in journal (Refereed)
    Abstract [en]

    Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95%-confidence intervals (95%-CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7±8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95%-CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95%-CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95%-CI 0.84-1.11) and tea (HR 0.97, 95%-CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggest that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.

  • 230. Ding, Yuan C
    et al.
    McGuffog, Lesley
    Healey, Sue
    Friedman, Eitan
    Laitman, Yael
    Paluch-Shimon, Shani-
    Kaufman, Bella
    Liljegren, Annelie
    Lindblom, Annika
    Olsson, Håkan
    Kristoffersson, Ulf
    Stenmark-Askmalm, Marie
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Domchek, Susan M
    Nathanson, Katherine L
    Rebbeck, Timothy R
    Jakubowska, Anna
    Lubinski, Jan
    Jaworska, Katarzyna
    Durda, Katarzyna
    Gronwald, Jacek
    Huzarski, Tomasz
    Cybulski, Cezary
    Byrski, Tomasz
    Osorio, Ana
    Cajal, Teresa Ramóny
    Stavropoulou, Alexandra V
    Benítez, Javier
    Hamann, Ute
    Rookus, Matti
    Aalfs, Cora M
    de Lange, Judith L
    Meijers-Heijboer, Hanne E J
    Oosterwijk, Jan C
    van Asperen, Christi J
    Gómez García, Encarna B
    Hoogerbrugge, Nicoline
    Jager, Agnes
    van der Luijt, Rob B
    Easton, Douglas F
    Peock, Susan
    Frost, Debra
    Ellis, Steve D
    Platte, Radka
    Fineberg, Elena
    Evans, D Gareth
    Lalloo, Fiona
    Izatt, Louise
    Eeles, Ros
    Adlard, Julian
    Davidson, Rosemarie
    Eccles, Diana
    Cole, Trevor
    Cook, Jackie
    Brewer, Carole
    Tischkowitz, Marc
    Godwin, Andrew K
    Pathak, Harsh
    Stoppa-Lyonnet, Dominique
    Sinilnikova, Olga M
    Mazoyer, Sylvie
    Barjhoux, Laure
    Léoné, Mélanie
    Gauthier-Villars, Marion
    Caux-Moncoutier, Virginie
    de Pauw, Antoine
    Hardouin, Agnès
    Berthet, Pascaline
    Dreyfus, Hélène
    Ferrer, Sandra Fert
    Collonge-Rame, Marie-Agnès
    Sokolowska, Johanna
    Buys, Saundra
    Daly, Mary
    Miron, Alex
    Terry, Mary Beth
    Chung, Wendy
    John, Esther M
    Southey, Melissa
    Goldgar, David
    Singer, Christian F
    Tea, Muy-Kheng Maria
    Gschwantler-Kaulich, Daphne
    Fink-Retter, Anneliese
    Hansen, Thomas V O
    Ejlertsen, Bent
    Johannsson, Oskar T
    Offit, Kenneth
    Sarrel, Kara
    Gaudet, Mia M
    Vijai, Joseph
    Robson, Mark
    Piedmonte, Marion R
    Andrews, Lesley
    Cohn, David
    Demars, Leslie R
    Disilvestro, Paul
    Rodriguez, Gustavo
    Toland, Amanda Ewart
    Montagna, Marco
    Agata, Simona
    Imyanitov, Evgeny
    Isaacs, Claudine
    Janavicius, Ramunas
    Lazaro, Conxi
    Blanco, Ignacio
    Ramus, Susan J
    Sucheston, Lara
    Karlan, Beth Y
    Gross, Jenny
    Ganz, Patricia A
    Beattie, Mary S
    Schmutzler, Rita K
    Wappenschmidt, Barbara
    Meindl, Alfons
    Arnold, Norbert
    Niederacher, Dieter
    Preisler-Adams, Sabine
    Gadzicki, Dorotehea
    Varon-Mateeva, Raymonda
    Deissler, Helmut
    Gehrig, Andrea
    Sutter, Christian
    Kast, Karin
    Nevanlinna, Heli
    Aittomäki, Kristiina
    Simard, Jacques
    Spurdle, Amanda B
    Beesley, Jonathan
    Chen, Xiaoqing
    Tomlinson, Gail E
    Weitzel, Jeffrey
    Garber, Judy E
    Olopade, Olufunmilayo I
    Rubinstein, Wendy S
    Tung, Nadine
    Blum, Joanne L
    Narod, Steven A
    Brummel, Sean
    Gillen, Daniel L
    Lindor, Noralane
    Fredericksen, Zachary
    Pankratz, Vernon S
    Couch, Fergus J
    Radice, Paolo
    Peterlongo, Paolo
    Greene, Mark H
    Loud, Jennifer T
    Mai, Phuong L
    Andrulis, Irene L
    Glendon, Gord
    Ozcelik, Hilmi
    Gerdes, Anne-Marie
    Thomassen, Mads
    Jensen, Uffe Birk
    Skytte, Anne-Bine
    Caligo, Maria A
    Lee, Andrew
    Chenevix-Trench, Georgia
    Antoniou, Antonis C
    Neuhausen, Susan L
    A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 8, p. 1362-1370Article in journal (Refereed)
    Abstract [en]

    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.

  • 231. Disney-Hogg, Linden
    et al.
    Cornish, Alex J.
    Sud, Amit
    Law, Philip J.
    Kinnersley, Ben
    Jacobs, Daniel I.
    Ostrom, Quinn T.
    Labreche, Karim
    Eckel-Passow, Jeanette E.
    Armstrong, Georgina N.
    Claus, Elizabeth B.
    Il'yasova, Dora
    Schildkraut, Joellen
    Barnholtz-Sloan, Jill S.
    Olson, Sara H.
    Bernstein, Jonine L.
    Lai, Rose K.
    Schoemaker, Minouk J.
    Simon, Matthias
    Hoffmann, Per
    Noethen, Markus M.
    Joeckel, Karl-Heinz
    Chanock, Stephen
    Rajaraman, Preetha
    Johansen, Christoffer
    Jenkins, Robert B.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wrensch, Margaret R.
    Sanson, Marc
    Bondy, Melissa L.
    Houlston, Richard S.
    Impact of atopy on risk of glioma: a Mendelian randomisation study2018In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, article id 42Article in journal (Refereed)
    Abstract [en]

    Background: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.

    Methods: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.

    Results: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).

    Conclusions: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.

  • 232.
    Djusberg, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Lundberg, Pia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High Levels of the AR-V7 Splice Variant and Co-Amplification of the Golgi Protein Coding YIPF6 in AR Amplified Prostate Cancer Bone Metastases2017In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 77, no 6, p. 625-638Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants and steroid-converting enzymes has been poorly examined. Specific aim was to examine AR amplification in PC bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying novel molecular targets for treatment. METHODS: Gene amplification was assessed by fluorescence in situ hybridization in cryo-sections of clinical PC bone metastases (n = 40) and by PCR-based copy number variation analysis. Whole genome mRNA expression was analyzed using H12 Illumina Beadchip arrays and specific transcript levels were quantified by qRT-PCR. Protein localization was analyzed using immunohistochemistry and confocal microscopy. The YIPF6 mRNA expression was transiently knocked down and stably overexpressed in the 22Rv1 cell line as representative for CRPC, and effects on cell proliferation, colony formation, migration, and invasion were determined in vitro. Extracellular vesicles (EVs) were isolated from cell cultures using size-exclusion chromatography and enumerated by nanoparticle tracking analysis. Protein content was identified by LC-MS/MS analysis. Blood coagulation was measured as activated partial thromboplastin time (APTT). Functional enrichment analysis was performed using the MetaCore software. RESULTS: AR amplification was detected in 16 (53%) of the bone metastases examined from CRPC patients (n = 30), and in none from the untreated patients (n = 10). Metastases with AR amplification showed high AR and AR-V7 mRNA levels, increased nuclear AR immunostaining, and co-amplification of genes such as YIPF6 in the AR proximity at Xq12. The YIPF6 protein was localized to the Golgi apparatus. YIPF6 overexpression in 22Rv1 cells resulted in reduced cell proliferation and colony formation, and in enhanced EV secretion. EVs from YIPF6 overproducing 22Rv1 cells were enriched for proteins involved in blood coagulation and, accordingly, decreased the APTT in a dose-dependent fashion. CONCLUSIONS: AR amplified CRPC bone metastases show high AR-V7 expression that probably gives resistance to AR-targeting drugs. Co-amplification of the Golgi protein coding YIPF6 gene with the AR may enhance the secretion of pro-coagulative EVs from cancer cells and thereby stimulate tumor progression and increase the coagulopathy risk in CRPC patients.

  • 233. Dobbins, Sara E.
    et al.
    Broderick, Peter
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Feychting, Maria
    Johansen, Christoffer
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Schramm, Johannes
    Olver, Bianca
    Lloyd, Amy
    Ma, Yussanne P.
    Hosking, Fay J.
    Lönn, Stefan
    Ahlbom, Anders
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schoemaker, Minouk J.
    Hepworth, Sarah J.
    Hoffmann, Per
    Muehleisen, Thomas W.
    Noethen, Markus M.
    Moebus, Susanne
    Eisele, Lewin
    Kosteljanetz, Michael
    Muir, Kenneth
    Swerdlow, Anthony
    Simon, Matthias
    Houlston, Richard S.
    Common variation at 10p12.31 near MLLT10 influences meningioma risk2011In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 43, no 9, p. 825-827Article in journal (Refereed)
    Abstract [en]

    To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.

  • 234. Dossus, Laure
    et al.
    Franceschi, Silvia
    Biessy, Carine
    Navionis, Anne-Sophie
    Travis, Ruth C
    Weiderpass, Elisabete
    Scalbert, Augustin
    Romieu, Isabelle
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Bonnet, Fabrice
    Fournier, Agnès
    Fortner, Renee T
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    La Vecchia, Carlo
    Peppa, Eleni
    Tumino, Rosario
    Panico, Salvatore
    Palli, Domenico
    Agnoli, Claudia
    Vineis, Paolo
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Skeie, Guri
    Zamora-Ros, Raul
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Sánchez, Maria-Jose
    Ramón Quirós, Jose
    Dorronsoro, Miren
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Schmidt, Julie A
    Khaw, Kay-Tee
    Tsilidis, Konstantinos K
    Aune, Dagfinn
    Riboli, Elio
    Rinaldi, Sabina
    Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 7, p. 1332-1342Article in journal (Refereed)
    Abstract [en]

    Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwide. Consistent evidence shows that body mass is positively associated with TC risk. As excess weight is a state of chronic inflammation, we investigated the relationship between concentrations of leptin, adiponectin, C-reactive protein, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α and the risk of TC. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study and included 475 first primary incident TC cases (399 women and 76 men) and 1,016 matched cancer-free cohort participants. Biomarkers were measured in serum samples using validated and highly sensitive commercially available immunoassays. Odds ratios (ORs) of TC by levels of each biomarker were estimated using conditional logistic regression models, adjusting for BMI and alcohol consumption. Adiponectin was inversely associated with TC risk among women (ORT3vs.T1  = 0.69, 95% CI: 0.49-0.98, Ptrend  = 0.04) but not among men (ORT3vs.T1  = 1.36, 95% CI: 0.67-2.76, Ptrend  = 0.37). Increasing levels of IL-10 were positively associated with TC risk in both genders and significantly so in women (ORT3vs.T1  = 1.59, 95% CI: 1.13-2.25, Ptrend  = 0.01) but not in men (ORT3vs.T1  = 1.78, 95% CI: 0.80-3.98, Ptrend  = 0.17). Leptin, CRP, IL-6 and TNF-α were not associated with TC risk in either gender. These results indicate a positive association of TC risk with IL-10 and a negative association with adiponectin that is probably restricted to women. Inflammation may play a role in TC in combination with or independently of excess weight.

  • 235. Dossus, Laure
    et al.
    McKay, James D
    Canzian, Federico
    Wilkening, Stefan
    Rinaldi, Sabina
    Biessy, Carine
    Olsen, Anja
    Tjønneland, Anne
    Jakobsen, Marianne U
    Overvad, Kim
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fournier, Agnes
    Linseisen, Jakob
    Lukanova, Annekatrin
    Boeing, Heiner
    Fisher, Eva
    Trichopoulou, Antonia
    Georgila, Christina
    Trichopoulos, Dimitrios
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Vineis, Paolo
    Quirós, José Ramon
    Sala, Núria
    Martínez-García, Carmen
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    van Duijnhoven, Fränzel J B
    Bueno-de-Mesquita, H B
    van Gils, Carla H
    Peeters, Petra H M
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bingham, Sheila
    Khaw, Kay Tee
    Key, Tim J
    Travis, Ruth C
    Ferrari, Pietro
    Jenab, Mazda
    Riboli, Elio
    Kaaks, Rudolf
    Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).2008In: Carcinogenesis, ISSN 1460-2180, Vol. 29, no 7, p. 1360-1366Article in journal (Refereed)
    Abstract [en]

    Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between <0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP < 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.

  • 236. du Bois, A
    et al.
    Sehouli, J
    Lund, B
    Joly, F
    Huober, J
    Jensen, T S
    Levy, E
    Heilmann, V
    Boman, Karin
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hardy-Bessard, A C
    Burges, A
    Mäenpää, J
    Pujade-Lauraine, E
    Pfisterer, J
    Gropp, M
    Staehle, A
    Wimberger, P
    Jackisch, C
    Schmalfeldt, B
    Belau, A
    Loibl, S
    Wollschlaeger, K
    Canzler, U
    Rochon, J
    Paclitaxel-carboplatin-gemcitabine (TCG) as first-line treatment of ovarian cancer: a prospective multicenter phase II study (AGO-OVAR 8) followed by a prospectively randomized phase III GCIG intergroup study (AGO-OVAR 9, GINECO-TCG, NSGO-OC-0102) comparing TCG with standard TC2005In: Int J Gynecol Cancer: Supplement 3, Vol. 15, p. 224-225Article in journal (Refereed)
  • 237.
    Duchek, Milos
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jahnson, Staffan
    Mestad, Oddvar
    Hellström, Pekka
    Hellsten, Sverker
    Malmström, Per-Uno
    Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study.2010In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed.

    OBJECTIVE: To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours.

    DESIGN, SETTING, AND PARTICIPANTS: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr.

    MEASUREMENTS: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented.

    RESULTS AND LIMITATIONS: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination.

    CONCLUSIONS: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 238. Duffy, S W
    et al.
    Lynge, E
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ayyaz, S
    Olsen, A H
    Complexities in the estimation of overdiagnosis in breast cancer screening.2008In: British journal of cancer, ISSN 1532-1827, Vol. 99, no 7, p. 1176-1178Article in journal (Refereed)
    Abstract [en]

    There is interest in estimating and attributing temporal changes in incidence of breast cancer in relation to the initiation of screening programmes, in particular to estimation of overdiagnosis of breast cancer as a result of screening. In this paper, we show how screening introduces complexities of analysis and interpretation of incidence data. For example, lead time brings forward time- and age-related increases in incidence. In addition, risk factors such as hormone replacement therapy use have been changing contemporaneously with the introduction of screening. Although we do not indicate exactly how such complexities should be corrected for, we use some simple informal adjustments to show how they may account for a substantial proportion of increased incidence, which might otherwise erroneously have been attributed to overdiagnosis. We illustrate this using an example of analysis of breast cancer incidence data from Sweden.

  • 239. Duffy, Stephen W
    et al.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Agbaje, Olorunsola F
    Pashayan, Nora
    Gabe, Rhian
    Avoiding bias from aggregate measures of exposure.2007In: J Epidemiol Community Health, ISSN 0143-005X, Vol. 61, no 5, p. 461-463Article in journal (Refereed)
  • 240. Duffy, SW
    et al.
    Chen, THH
    Smith, RA
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Törnberg, S
    Frisell, J
    Holmberg, L
    Effect of mammographic service screening on stage at presentation of breast cancers in Sweden.2007In: Cancer, ISSN 0008-543X, Vol. 109, no 11, p. 2205-2212Article in journal (Refereed)
  • 241. Duffy, SW
    et al.
    Lynge, E
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Reply: estimation of lead-time and overdiagnosis in breast cancer screening2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 1, p. 220-220Article in journal (Other academic)
  • 242. Duffy, SW
    et al.
    Tabar, L
    Chen, THH
    Smith, RA
    Holmberg, L
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Törnberg, S
    Reduction in Breast Cancer Mortality from the Organised Service Screening with Mammography:: 2. Validation with Alternative Analytic Methods2006In: Cancer Epidemiology Biomarkers & Prevention, Vol. 15, p. 52-56Article in journal (Refereed)
  • 243. Early Breast Cancer Trialists' Collaborative Group, EBCTCG
    et al.
    Bengtsson, Nils-Olof
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Larsson, Lars-Gunnar
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.2005In: The Lancet, ISSN 0140-6736, Vol. 366, no 9503, p. 2087-2106Article in journal (Refereed)
  • 244. Eckel-Passow, Jeanette
    et al.
    Decker, Paul
    Kosel, Matthew
    Kollmeyer, Thomas
    Sarkar, Gobinda
    Caron, Alissa
    Bracci, Paige
    Hansen, Helen
    Madsen, Nils
    McCoy, Lucie
    Molinaro, Annette
    Rice, Terri
    Walsh, Kyle
    Giannini, Caterina
    Parney, Ian
    Wiemels, Joseph
    Wiencke, John
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    Lachance, Daniel
    Wrensch, Margaret
    Jenkins, Robert
    ASSOCIATION OF KNOWN GLIOMA GERMLINE RISK SNPs WITHIN MOLECULARLY-DEFINED GROUPS2016In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 18, p. 57-57Article in journal (Refereed)
  • 245. Edlinger, Michael
    et al.
    Strohmaier, Susanne
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bjørge, Tone
    Manjer, Jonas
    Borena, Wegene T
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Engeland, Anders
    Tretli, Steinar
    Concin, Hans
    Nagel, Gabriele
    Selmer, Randi
    Johansen, Dorthe
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ulmer, Hanno
    Blood pressure and other metabolic syndrome factors and risk of brain tumour in the large population-based Me-Can cohort study2012In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, no 2, p. 290-296Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:: Brain tumour has few established determinants. We assessed to which extent risk of brain tumour was related to metabolic syndrome factors in adults. METHODS:: In the Me-Can project, 580 000 individuals from Sweden, Austria, and Norway were followed for a median of 10 years after baseline measurement. Data on brain tumours were obtained from national cancer registries. The factors of metabolic syndrome (BMI, SBP and DBP, and blood levels of glucose, cholesterol, and triglycerides), separately and combined, were analysed in quintiles and for transformed z-scores (mean transformed to 0 and standard deviation to 1). Cox proportional hazards multivariate regression models were used, with corrections for measurement error. RESULTS:: During follow-up, 1312 primary brain tumours were diagnosed, predominantly meningioma (n = 348) and high-grade glioma (n = 436). For meningioma, the hazard ratio was increased for z-scores of SBP [hazard ratio = 1.27 per unit standard deviation, 95% confidence interval (CI) 1.03-1.57], of DBP (hazard ratio = 1.29, 95% CI 1.04-1.58), and of the combined metabolic syndrome score (hazard ratio = 1.31, 95% CI 1.11-1.54). An increased risk of high-grade glioma was found for DBP (hazard ratio = 1.23, 95% CI 1.01-1.50) and triglycerides (hazard ratio = 1.35, 95% CI 1.05-1.72). For both meningioma and high-grade glioma, the risk was more than double in the fifth quintiles of DBP compared to the lowest quintile. For meningioma this risk was even larger for SBP. CONCLUSION:: Increased blood pressure was associated with risk of brain tumours, especially of meningiomas.

  • 246. Edlund, Per
    et al.
    Ahlgren, Johan
    Bjerre, Karsten
    Andersson, Michael
    Bergh, Jonas
    Mouridsen, Henning
    Holmberg, Stig B
    Bengtsson, Nils-Olof
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jakobsen, Erik
    Møller, Susanne
    Lindman, Henrik
    Blomqvist, Carl
    Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-12011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no 3, p. 329-337Article in journal (Refereed)
    Abstract [en]

    The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer. Patients and methods. After a first standard dosed FEC course (5-fluorouracil 600 mg/m2, epirubicin 60 mg/mg2 and cyclophosphamide 600 mg/m2), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2–7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered). Results. Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III–IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. Conclusion. Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.Read More: http://informahealthcare.com/doi/abs/10.3109/0284186X.2011.554435

  • 247.
    Edwinsdotter Ardnor, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rosén, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The BRCA1 exon 13 duplication: clinical characteristics of 22 families in Northern Sweden2019In: Familial Cancer, ISSN 1389-9600, E-ISSN 1573-7292, Vol. 18, no 1, p. 37-42Article in journal (Refereed)
    Abstract [en]

    The clinical management of BRCA1/2 mutation carriers requires accurate cancer risk estimates. Cancer risks vary according to type and location of the mutation and since there is limited information about mutation-specific cancer risks, genotype-phenotype correlation studies are needed. This is a report of 22 families with the same mutation, BRCA1 duplication exon 13, a mutation that is found world-wide, with the objective to describe the cancer history found in these families. We studied 69 confirmed carriers, 53 women and 16 men, and additionally 29 women who were clinically expected carriers. Among the confirmed carriers, 27 women (51%) were diagnosed with breast cancer, 10 (19%) with ovarian cancer, 5 (9%) with breast and ovarian cancer and 17 (32%) without cancer. Nine women (17%) with breast cancer were 35 years or younger at diagnose. Also, two cases of early onset colon cancer were found, and 37,5% of the male carriers were diagnosed with prostate cancer. These data may have implications for risk assessment and cancer prevention decision making for carriers of the BRCA1 duplication exon 13 mutation.

  • 248.
    Egberg Thyme, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    What do you see?: studies on time-limited psychodynamic art psychotherapy2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main purpose of this thesis is to explore experiences of two different psychological interventions based on art psychotherapy in women with a psychological or physical illness. The two interventions are art psychotherapy and art therapy. The difference between these two interventions is that the art therapist works with the transference in art psychotherapy but not in art therapy. The thesis consists of two studies of art psychotherapy: An art psychotherapy intervention is evaluated in Study 1 (papers III and V) which examines a group of patients diagnosed with depression and Study 2 (paper II) which examines experiences in a group of six patients diagnosed with vulva vestibulitis. An art therapy intervention is evaluated in the third study (papers I and IV); where experiences in patients diagnosed with breast cancer are examined.

    In Study 1, forty-three (n=43) depressed women were randomly assigned to either an intervention group or a control group (verbal psychotherapy). The aim was to examine the outcome of time limited psychodynamic art therapy compared to time-limited psychodynamic verbal therapy for patients with depressive symptoms. Interviews were performed before, immediately after, and three months after the termination of psychotherapy, and self-rating scales which focus on stress reactions, depression and symptoms as well as an observer rating scale on depression were used. The interviews and the art sessions were video-recorded, and the verbal psychotherapy was tape-recorded. The results showed that the art and verbal psychotherapies were comparable. The conclusion was that short-term psychodynamic art psychotherapy could be a valuable treatment for depressed women. In an in-depth content analysis, the method of scribbling was further investigated and exemplified with the therapies of two participants. In this study, the patients’ pictures and verbal expressions of progress, along with considerations of how to interpret the pictures were in focus. When leaving therapy the two patients took advantage of the paper, made complete forms, symbolised in words what they have expressed in pictures; in pace with psychotherapy the themes alter towards separation, individuation, and attempt to relate in a new way. The conclusion was that limelimited psychodynamic art therapy suggests giving a safer place for the self as the cohesion is firmer with better boundaries.

    Study 2 is a pilot study, which involved six young patients newly diagnosed with vulva vestibulitis. The aim of the study was to investigate pain at vestibulum, mental health, and self-image after fifteen sessions of art psychotherapy. Five of the patients were judged to have less pain three months after termination of therapy. The conclusion was that art psychotherapy with its openness seemed to affect young women in their experiences of vulva vestibulitis in a positive direction.

    Study 3 examined the potential benefit of art therapy for women with primary breast cancer. The sample comprised forty-one (n=41) patients who were randomly assigned either to an art therapy group or to a control group. The art therapy was going on during five weeks radiation treatment, one session per week. The aim was to investigate the outcome of art therapy, to quantify and compare the participant coping s, self-image, and the symptoms with the participant in the control group. Interviews were performed before, immediately after, and six month after inclusion. A set of self-rating scales was used: Coping Resources Inventory, the Structural Analysis of Social Behavior, and Symptom Check List – 90. The result showed that the patients in the art therapy group rated their coping s and especially their social s, higher than the control group, and that the average patients in the art therapy group improved in depressive symptoms and symptoms of anxiety, and that the general psychiatric symptoms improved as well. A linear regression analysis showed a tendency that the coping s increased in the art therapy group and decreased in the control group or even stagnated in the social domain. A second report on self-image, symptoms, treatment, and social variables showed that art therapy was related to lower ratings of depression, anxiety, and general symptoms after treatment; chemotherapeutic treatment predicted lower depressive symptoms and general symptoms in contrast to axilliary surgery and hormonal treatment. The results showed that art therapy could be valuable complementary therapy in routine oncology practise. The conclusion is that art therapy can have a positive long-term effect on the crisis following the primary breast cancer and its consequences.

    Conclusion: The results show that time-limited psychodynamic art psychotherapy is valuable for depressed women; that it is a valuable complement for women with vulva vestibulitis; and that art therapy is a valuable complement in the care and cure of women with primary breast cancer.

  • 249.
    Egberg Thyme, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Sundin, Eva C.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Wiberg, Britt
    Division of Psychology, Nottingham Trent University, Nottinham, United Kingdom.
    Öster, Inger
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Åström, Sture
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Individual brief art therapy can be helpful for women with breast cancer: A randomized controlled clinical study2009In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 7, no 1, p. 87-95Article in journal (Refereed)
    Abstract [en]

    Objective: Recent research shows that almost every second woman with breast cancer is depressed or has anxiety; the risk for younger women is even higher. Moreover, research shows that women are at risk for developing depression, also a threat for women with breast cancer. The aim of this randomized controlled clinical trial was to study the outcome of five sessions of art therapy given at a 5-week period of postoperative radiotherapy.

    Methods: The participants were between 37 and 69 years old; six participants in each group were below 50 years of age. Half of the participants (n = 20) received art therapy and the other half (n = 21) were assigned to a control group. At the first measurement, at least 17% (n = 7) of the participants medicated with antidepressants. Data were collected before and after art therapy and at a 4-month follow-up using self-rating scales that measure self-image (the Structural Analysis of Social Behaviour) and psychiatric symptoms (the Symptom Check List–90).

    Results: At follow-up, significant lower ratings of depression, anxiety, and somatic symptoms and less general symptoms were reported for the art therapy group compared to the control group. The regression analysis showed that art therapy relates to lower ratings of depression, anxiety, and general symptoms; chemotherapeutic treatment predicts lower depressive symptoms; in contrast to axilliary surgery and hormonal treatment as well as being a parent predicts higher ratings of anxiety and general symptoms.

    Significance of results: The conclusion suggests that art therapy has a long-term effect on the crisis following the breast cancer and its consequences.

  • 250.
    Egberg Thyme, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wiberg, Britt
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Sundin, Eva
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    The entangled butterfly and the blue cactus: two case studies on time-limited psychodynamic art psychotherapyManuscript (Other academic)
    Abstract [en]

    The aim of these two case studies is an in-depth analysis of the practice of scribbling in time- limited psychodynamic art psychotherapy. Our hypothesis is that the answers to "What do you see?" change as therapy proceeds, due to changes in emotions and cognitions expressed in scribbles and amplifications. The treatment is one hour per week for ten weeks, exempli- fied by two women with depression selected for differences in age, demographics and art expression. Analysis of the pictures and words is in two steps. The pictures were first tran- scribed into words using a phenomenological approach and then analysed according to con- tent analysis. Correspondingly, the words of the sessions were first transcribed verbatim and then analysed according to content analysis. The results show that the even if the two women have the same diagnosis at inclusion according to DSM IV, the symptoms of depression are expressed differently both in how they are manifested and in latent messages in the content analysis. The two women’s therapies can be divided into three phases each marked by turning points in the pictures – hence the pictures rather than the words set the theme for the phase. On leaving therapy the patients are able to use their drawings, their amplifications are in a complete form, they symbolise in words what they have expressed in pictures.

    The study’s conclusion is that the practice of scribbling seems to give a better capacity to regulate affects and, hence, a better regulation of the self. The women used not only their intellects but also their bodies in making latent communications manifest; their self-esteem improved as therapy proceeded, and they regained a sensitivity of "me – not me", i.e. better boundaries. The clinical implications are that the time-limited model of art psychotherapy is well suited to process emotions connected with depression, and that the patient’s problem should determine the length of the time limit.

     

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