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  • 1251. Wilkening, Stefan
    et al.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Canzian, Federico
    Enquist, Kerstin
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Patologi.
    Altieri, Andrea
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hemminki, Kari
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Försti, Asta
    Interleukin promoter polymorphisms and prognosis in colorectal cancer.2008In: Carcinogenesis, ISSN 1460-2180, Vol. 29, no 6, p. 1202-1206Article in journal (Refereed)
    Abstract [en]

    There is strong evidence that cancer-associated inflammation promotes tumor growth and progression. This is especially true for colorectal cancer (CRC). Interleukins (ILs) are important modulators for inflammation. We examined whether promoter polymorphisms in key IL genes (IL4, IL4R, IL6, IL8 and IL10) are associated with the risk or clinical outcome of CRC. Five single-nucleotide polymorphisms (SNPs) were analyzed in genomic DNA from a cohort including 308 Swedish incident cases of CRC with data on Dukes' stage and up to 16 years of follow-up and 585 healthy controls. The selected SNPs have previously been shown to be functional and/or associated with cancer. None of the analyzed SNPs associated with the risk of CRC. When stratifying by tumor stage, significantly more patients carrying at least one G allele of IL10-1082 had tumors with Dukes' stages A + B than with stages C + D (P(trend) = 0.035 for genotype distribution). Analyzing associations with overall survival time, we found the rare T allele of IL4-590 to be related to a longer survival [CT versus CC Cox proportional hazard ratio 0.69, 95% confidence intervals 0.46-1.03, TT versus CC 0.32 (0.10-1.03)]. For IL6-174, the CG genotype was associated with a longer survival when compared with the CC genotype [0.64 (0.40-1.01)]. The present study was particularly suitable for survival analysis because all patients were sampled before the diagnosis of CRC. Our results suggest that the SNPs IL4-590 and IL6-174 may be useful markers for CRC prognosis. The predicted biological effect of these SNPs in relation to promotion of cancer progression is consistent with the observed increased survival time.

  • 1252. Williams, Jon P
    et al.
    Wu, Jianqiang
    Johansson, Gunnar
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University.
    Rizvi, Tilat A
    Miller, Shyra C
    Geiger, Hartmut
    Malik, Punam
    Li, Wenling
    Mukouyama, Yoh-suke
    Cancelas, Jose A
    Ratner, Nancy
    Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor that confers neurofibroma tumorigenic potential.2008In: Cell stem cell, ISSN 1875-9777, Vol. 3, no 6, p. 658-69Article in journal (Refereed)
    Abstract [en]

    Defining growth factor requirements for progenitors facilitates their characterization and amplification. We characterize a peripheral nervous system embryonic dorsal root ganglion progenitor population using in vitro clonal sphere-formation assays. Cells differentiate into glial cells, smooth muscle/fibroblast (SM/Fb)-like cells, and neurons. Genetic and pharmacologic tools revealed that sphere formation requires signaling from the EGFR tyrosine kinase. Nf1 loss of function amplifies this progenitor pool, which becomes hypersensitive to growth factors and confers tumorigenesis. DhhCre;Nf1(fl/fl) mouse neurofibromas contain a progenitor population with similar growth requirements, potential, and marker expression. In humans, NF1 mutation predisposes to benign neurofibromas, incurable peripheral nerve tumors. Prospective identification of human EGFR(+);P75(+) neurofibroma cells enriched EGF-dependent sphere-forming cells. Neurofibroma spheres contain glial-like progenitors that differentiate into neurons and SM/Fb-like cells in vitro and form benign neurofibroma-like lesions in nude mice. We suggest that expansion of an EGFR-expressing early glial progenitor contributes to neurofibroma formation.

  • 1253.
    Willén, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Center for Research and Development, Uppsala University/Region Gävleborg, Sweden; Department of Oncology, Gävle Hospital, Gävle, Sweden.
    Berglund, Anders
    Epistat, Uppsala.
    Bergström, Stefan
    Centrum för forskning och utveckling Region Gävleborg.
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Center for Research and Development, Uppsala University/Region Gävleborg, Sweden; Department of Oncology, Gävle Hospital, Gävle, Sweden.
    Öjdahl-Boden, Anna
    Department of Respiratory diseases, Karolinska universitetssjukhuset i Huddinge.
    Wagenius, Gunnar
    Division of Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Regional Cancer Center Uppsala Örebro, Uppsala, Sweden.
    Educational level and management and outcomes in non-small cell lung cancer. A nationwide population-based study2019In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 131, p. 40-46Article in journal (Refereed)
    Abstract [en]

    Objectives: We examined associations between educational level and clinical presentation, patterns of management and mortality in patients with non-small cell lung cancer (NSCLC) in Sweden, a country with a National Health Care System.

    Materials and Methods: We identified 39,671 patients with a NSCLC diagnosis 2002–2016 in Lung Cancer Data Base Sweden (LCBaSe), a population-based research database. In analyses adjusted for comorbidity and other prognostic factors, odds Ratios (OR) and hazard Ratios (HR) were estimated to examine associations between patients’ educational level and aspects of management and mortality.

    Results: Stage at diagnosis and waiting times did not differ between educational groups. In multivariable analysis, the likelihood to undergo PET/CT and assessment in a multidisciplinary team setting were higher in patients with high compared to low education (aOR 1.14; CI 1.05–1.23 and aOR 1.22; CI 1.14–1.32, respectively). In patients with early stage IA-IIB disease, the likelihood to undergo stereotactic radiotherapy was elevated in patients with high education (aOR 1.40; CI 1.03–1.91). Both all-cause (aHR 0.86; CI 0.77-0.92) and cause-specific mortality (aHR 0.83; CI 0.74-0.92) was lower in patients with high compared to low education in early stage disease (IA-IIB). In higher stage NSCLC no differences were observed. Patterns were similar in separate assessments stratified by sex and histopathology.

    Conclusions: While stage at diagnosis and waiting times did not differ between educational groups, we found socioeconomic differences in diagnostic intensity, multidisciplinary team assessment, stereotactic radiotherapy and mortality in patients with NSCLC. These findings may in part reflect social gradients in implementation and use of novel diagnostic and treatment modalities. Our findings underscore the need for improved adherence to national guidelines.

  • 1254.
    Willén, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centrum för forskning och utveckling Region Gävleborg.
    Isaksson, Johan
    Centrum för forskning och utveckling Region Gävleborg; Uppsala Universitet.
    Bergström, Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centrum för forskning och utveckling Region Gävleborg.
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Centrum för forskning och utveckling Region Gävleborg.
    Berglund, Anders
    Epistat, Uppsala.
    Öjdahl-Boden, Anna
    Wagenius, Gunnar
    Nationella lungcancerregistret.
    Lambe, Mats
    Medicinsk epidemiologi och biostatistik, Karolinska institutet; Regionalt cancercentrum Uppsala-Örebro.
    Små och minskande skillnader i lungcancervården2019In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518Article in journal (Other academic)
  • 1255. Wilson, Lauren E.
    et al.
    Xu, Zongli
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    White, Alexandra J.
    Troester, Melissa A.
    Sandler, Dale P.
    Taylor, Jack A.
    Alcohol and DNA Methylation: An Epigenome-Wide Association Study in Blood and Normal Breast Tissue2019In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, no 6, p. 1055-1065Article in journal (Refereed)
    Abstract [en]

    The biological mechanisms driving associations between alcohol consumption and chronic diseases might include epigenetic modification of DNA methylation. We explored the hypothesis that alcohol consumption is associated with methylation in an epigenome-wide association study of blood and normal breast tissue DNA. Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, California) array data on blood DNA methylation was examined in a discovery set of 2,878 non-Hispanic white women from the Sister Study (United States, 2004-2015) who provided detailed questionnaire information on lifetime alcohol use. Robust linear regression modeling was used to identify significant associations (false discovery rate of Q < 0.05) between the number of alcoholic drinks per week and DNA methylation at 5,458 cytosine-phosphate-guanine (CpG) sites. Associations were replicated (P < 0.05) for 677 CpGs in an independent set of 187 blood DNA samples from the Sister Study and for 628 CpGs in an independent set of 171 normal breast DNA samples; 1,207 CpGs were replicated in either blood or normal breast, with 98 CpGs replicated in both tissues. Individual gene effects were notable for phosphoglycerate dehydrogenase (PGHDH), peptidyl-prolyl cis-trans isomerase (PPIF), solute carrier 15 (SLC15), solute carrier family 43 member 1 (SLC43A1), and solute carrier family 7 member 11 (SLC7A11). We also found that high alcohol consumption was associated with significantly lower global methylation as measured by the average of CpGs on the entire array.

  • 1256. Winqvist, Maria
    et al.
    Andersson, Per-Ola
    Asklid, Anna
    Karlsson, Karin
    Karlsson, Claes
    Lauri, Birgitta
    Lundin, Jeanette
    Mattsson, Mattias
    Norin, Stefan
    Sandstedt, Anna
    Rosenquist, Richard
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hansson, Lotta
    Österborg, Anders
    Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort2019In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 104, no 5, p. E208-E210Article in journal (Refereed)
  • 1257.
    Wirén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ulmer, Hanno
    Manjer, Jonas
    Bjørge, Tone
    Nagel, Gabriele
    Johansen, Dorthe
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Engeland, Anders
    Concin, Hans
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Selmer, Randi
    Tretli, Steinar
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Pooled cohort study on height and risk of cancer and cancer death2014In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 2, p. 151-159Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To assess the association between height and risk of cancer and cancer death.

    METHODS: The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model.

    RESULTS: During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06-1.09), and in men, HR 1.04 (95 % CI 1.03-1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11-1.24), and in men HR 1.12 (95 % CI 1.08-1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01-1.16), and in men, HR 1.03 (95 % CI 1.01-1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00-1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07-1.30). All these associations were independent of body mass index.

    CONCLUSION: Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.

  • 1258. Woltmann, Andrea
    et al.
    Chen, Bowang
    Lascorz, Jesus
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eyfjord, Jorunn E.
    Hamann, Ute
    Manjer, Jonas
    Enquist-Olsson, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herms, Stefan
    Hoffmann, Per
    Hemminki, Kari
    Lenner, Per
    Forsti, Asta
    Systematic Pathway Enrichment Analysis of a Genome-Wide Association Study on Breast Cancer Survival Reveals an Influence of Genes Involved in Cell Adhesion and Calcium Signaling on the Patients' Clinical Outcome2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, p. e98229-Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The goal was to identify the functional categories (GO terms and KEGG pathways) that are consistently overrepresented in a statistically significant way in the list of genes generated from the single nucleotide polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01 were annotated to the genes by excluding or including a 20 kb up-and down-stream sequence of the genes and analyzed by six different tools. We identified eleven consistently enriched categories, the most significant ones relating to cell adhesion and calcium ion binding. Moreover, we investigated the similarity between our GWAS and the enrichment analyses of twelve published gene expression signatures for breast cancer prognosis. Five of them were commonly used and commercially available, five were based on different aspects of metastasis formation and two were developed from meta-analyses of published prognostic signatures. This comparison revealed similarities between our GWAS data and the general and the specific brain metastasis gene signatures as well as the Oncotype DX signature. As metastasis formation is a strong indicator of a patient's prognosis, this result reflects the survival aspect of the conducted GWAS and supports cell adhesion and calcium signaling as important pathways in cancer progression.

  • 1259.
    Wu, Wendy Yi-Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tabar, Laszlo
    Tot, Tibor
    Fann, Ching-Yuan
    Yen, Amy Ming-Fang
    Chen, Sam Li-Sheng
    Chiu, Sherry Yueh-Hsia
    Ku, May Mei-Sheng
    Hsu, Chen-Yang
    Beckmann, Kerri R.
    Smith, Robert A.
    Duffy, Stephen W.
    Chen, Hsiu-Hsi
    Imaging Biomarkers as Predictors for Breast Cancer Death2019In: Journal of Oncology, ISSN 1687-8450, E-ISSN 1687-8469, article id 2087983Article in journal (Refereed)
    Abstract [en]

    Background. To differentiate the risk of breast cancer death in a longitudinal cohort using imaging biomarkers of tumor extent and biology, specifically, the mammographic appearance, basal phenotype, histologic tumor distribution, and conventional tumor attributes. Methods. Using a prospective cohort study design, 498 invasive breast cancer patients diagnosed between 1996 and 1998 were used as the test cohort to assess the independent effects of the imaging biomarkers and other predictors on the risk of breast cancer death. External validation was performed with a cohort of 848 patients diagnosed between 2006 and 2010. Results. Mammographic tumor appearance was an independent predictor of risk of breast cancer death (P=0.0003) when conventional tumor attributes and treatment modalities were controlled. The casting type calcifications and architectural distortion were associated with 3.13-fold and 3.19-fold risks of breast cancer death, respectively. The basal phenotype independently conferred a 2.68-fold risk compared with nonbasal phenotype. The observed deaths did not differ significantly from expected deaths in the validation cohort. The application of imaging biomarkers together with other predictors classified twelve categories of risk for breast cancer death. Conclusion. Combining imaging biomarkers such as the mammographic appearance of the tumor with the histopathologic distribution and basal phenotype, accurately predicted long-term risk of breast cancer death. The information may be relevant for determining the need for molecular testing, planning treatment, and determining the most appropriate clinical surveillance schedule for breast cancer patients.

  • 1260.
    Wu, Wendy Yi-Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Törnberg, Sven
    Elfström, Klara Miriam
    Liu, Xijia
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Overdiagnosis in the population-based organized breast cancer screening program estimated by a non-homogeneous multi-state model: a cohort study using individual data with long-term follow-up2018In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 20, article id 153Article in journal (Refereed)
    Abstract [en]

    Background: Overdiagnosis, defined as the detection of a cancer that would not become clinically apparent in a woman’s lifetime without screening, has become a growing concern. Similar underlying risk of breast cancer in the screened and control groups is a prerequisite for unbiased estimates of overdiagnosis, but a contemporary control group is usually not available in organized screening programs.

    Methods: We estimated the frequency of overdiagnosis of breast cancer due to screening in women 50–69 years old by using individual screening data from the population-based organized screening program in Stockholm County 1989–2014. A hidden Markov model with four latent states and three observed states was constructed to estimate the natural progression of breast cancer and the test sensitivity. Piecewise transition rates were used to consider the time-varying transition rates. The expected number of detected non-progressive breast cancer cases was calculated.

    Results: During the study period, 2,333,153 invitations were sent out; on average, the participation rate in the screening program was 72.7% and the average recall rate was 2.48%. In total, 14,648 invasive breast cancer cases were diagnosed; among the 8305 screen-detected cases, the expected number of non-progressive breast cancer cases was 35.9, which is equivalent to 0.43% (95% confidence interval (CI) 0.10%–2.2%) overdiagnosis. The corresponding estimates for the prevalent and subsequent rounds were 15.6 (0.87%, 95% CI 0.20%–4.3%) and 20.3 (0.31%, 95% CI 0.07%–1.6%), respectively. The likelihood ratio test showed that the non-homogeneous model fitted the data better than an age-homogeneous model (P<0.001).

    Conclusions: Our findings suggest that overdiagnosis in the organized biennial mammographic screening for women 50–69 in Stockholm County is a minor phenomenon. The frequency of overdiagnosis in the prevalent screening round was higher than that in subsequent rounds. The non-homogeneous model performed better than the simpler, traditional homogeneous model.

  • 1261.
    Wu, Wendy Y-Y
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Estimation of overdiagnosis in breast cancer screening using a non-homogeneous multi-state model: a simulation study2018In: Journal of Medical Screening, ISSN 0969-1413, E-ISSN 1475-5793, Vol. 25, no 4, p. 183-190Article in journal (Refereed)
    Abstract [en]

    Objectives: Overdiagnosis is regarded as a harm of screening. We aimed to develop a non-homogeneous multi-state model to consider the age-specific transition rates for estimation of overdiagnosis, to validate the model by a simulation study where the true frequency of overdiagnosis can be calculated, and to compare our estimate with the cumulative incidence method. Methods: We constructed a four-state model to describe the natural history of breast cancer. The latent disease progression and the observed states for each individual were simulated in a trial with biennial screening of women aged 51-69 and a control group of the same size without screening. We performed 100 repetitions of the simulation with one million women to evaluate the performance of estimates. A sensitivity analysis with reduced number of controls was performed to imitate the data from the service screening programme. Results Based on the 100 repetitions, the mean value of the true frequency of overdiagnosis was 12.5% and the average estimates by the cumulative incidence method and the multi-state model were 12.9% (interquartile range: 2.46%) and 13.4% (interquartile range: 2.16%), respectively. The multi-state model had a greater bias of overdiagnosis than the cumulative incidence method, but the variation in the estimates was smaller. When the number of unscreened group was reduced, the variation of multi-state model estimates increased. Conclusions: The multi-state model produces a proper estimate of overdiagnosis and the results are comparable with the cumulative incidence method. The multi-state model can be used in the estimation of overdiagnosis, and might be useful for the ongoing service screening programmes.

  • 1262. Wu, Xuping
    et al.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergqvist, Michael
    Bergström, Stefan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gullbo, Joachim
    Lennartsson, Johan
    Hesselius, Patrik
    Ekman, Simon
    Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity.2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 1, p. 69-76Article in journal (Refereed)
    Abstract [en]

    Abstract Background. Leucine-rich and immunoglobulin-like domains 1-3 (LRIG1-3) proteins have been implicated in the regulation of EGFR signalling. In the present study, we investigated the clinical implications of the expression of EGFR and LRIG1-3 in oesophageal carcinoma, as well as the correlation between their expression levels and the chemosensitivity of oesophageal carcinoma cell lines. Patients and methods. Tumours from 80 patients with oesophageal carcinoma were investigated for the expression of EGFR and LRIG proteins by immunohistochemistry. Oesophageal carcinoma cell lines were investigated for their expression of EGFR and LRIG1, 2, and 3 by quantitative real time RT-PCR and for their sensitivity to commonly used chemotherapeutics by a cytotoxicity assay. Results and discussion: Based on a total score of intensity and expression rates, a trend towards survival difference was found for EGFR (p = 0.09) and LRIG2 (p = 0.18) whereas for LRIG1 and -3 there was no trend towards any association with survival. Correlation analysis revealed a correlation with the clinical expression of EGFR and LRIG3 (p = 0.0007). Significant correlations were found between LRIG1 expression levels and sensitivity to cisplatin (r = -0.74), docetaxel (r = -0.69), and vinorelbine (r = -0.82) in oesophageal carcinoma cell lines. EGFR and the LRIG proteins may be functionally involved in oesophageal carcinoma, but larger materials are needed to fully elucidate the clinical implication.

  • 1263.
    Wänman, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Grabowski, Pawel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Nyström, Helena
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Gustafsson, Patrik
    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.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Metastatic spinal cord compression as the first sign of malignancy: Outcome after surgery in 69 patients2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 4, p. 457-462Article in journal (Refereed)
    Abstract [en]

    Background and purpose - Metastatic spinal cord compression (MSCC) as the initial manifestation of malignancy (IMM) limits the time for diagnostic workup; most often, treatment is required before the final primary tumor diagnosis. We evaluated neurological outcome, complications, survival, and the manner of diagnosing the primary tumor in patients who were operated for MSCC as the IMM.

    Patients and methods - Records of 69 consecutive patients (51 men) who underwent surgery for MSCC as the IMM were reviewed. The patients had no history of cancer when they presented with pain (n = 2) and/or neurological symptoms (n = 67).

    Results - The primary tumor was identified in 59 patients. In 10 patients, no specific diagnosis could be established, and they were therefore defined as having cancer of unknown primary tumor (CUP). At the end of the study, 16 patients were still alive (median follow-up 2.5 years). The overall survival time was 20 months. Patients with CUP had the shortest survival (3.5 months) whereas patients with prostate cancer (6 years) and myeloma (5 years) had the longest survival. 20 of the 39 patients who were non-ambulatory preoperatively regained walking ability, and 29 of the 30 ambulatory patients preoperatively retained their walking ability 1 month postoperatively. 15 of the 69 patients suffered from a total of 20 complications within 1 month postoperatively.

    Interpretation - Postoperative survival with MSCC as the IMM depends on the type of primary tumor. Surgery in these patients maintains and improves ambulatory function.

  • 1264. Xu, Jianfeng
    et al.
    Dimitrov, Latchezar
    Chang, Bao-Li
    Adams, Tamara S
    Turner, Aubrey R
    Meyers, Deborah A
    Eeles, Rosalind A
    Easton, Douglas F
    Foulkes, William D
    Simard, Jacques
    Giles, Graham G
    Hopper, John L
    Mahle, Lovise
    Moller, Pal
    Bishop, Tim
    Evans, Chris
    Edwards, Steve
    Meitz, Julia
    Bullock, Sarah
    Hope, Questa
    Hsieh, Chih-Lin
    Halpern, Jerry
    Balise, Raymond N
    Oakley-Girvan, Ingrid
    Whittemore, Alice S
    Ewing, Charles M
    Gielzak, Marta
    Isaacs, Sarah D
    Walsh, Patrick C
    Wiley, Kathleen E
    Isaacs, William B
    Thibodeau, Stephen N
    McDonnell, Shannon K
    Cunningham, Julie M
    Zarfas, Katherine E
    Hebbring, Scott
    Schaid, Daniel J
    Friedrichsen, Danielle M
    Deutsch, Kerry
    Kolb, Suzanne
    Badzioch, Michael
    Jarvik, Gail P
    Janer, Marta
    Hood, Leroy
    Ostrander, Elaine A
    Stanford, Janet L
    Lange, Ethan M
    Beebe-Dimmer, Jennifer L
    Mohai, Caroline E
    Cooney, Kathleen A
    Ikonen, Tarja
    Baffoe-Bonnie, Agnes
    Fredriksson, Henna
    Matikainen, Mika P
    Tammela, Teuvo Lj
    Bailey-Wilson, Joan
    Schleutker, Johanna
    Maier, Christiane
    Herkommer, Kathleen
    Hoegel, Josef J
    Vogel, Walther
    Paiss, Thomas
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Stenman, Elisabeth
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Jonsson, Björn-Anders
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Camp, Nicola J
    Farnham, James
    Cannon-Albright, Lisa A
    Seminara, Daniela
    A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics2005In: Am J Hum Genet, ISSN 0002-9297, Vol. 77, no 2, p. 219-229Article in journal (Refereed)
  • 1265. Xu, Jianfeng
    et al.
    Lowey, James
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Sun, Jielin
    Lindmark, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Hsu, Fang-Chi
    Dimitrov, Latchezar
    Chang, Baoli
    Turner, Aubrey R
    Liu, Wennan
    Adami, Hans-Olov
    Suh, Edward
    Moore, Jason H
    Zheng, S Lilly
    Isaacs, William B
    Trent, Jeffrey M
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk2005In: Cancer Epidemiol Biomarkers Prev, ISSN 1055-9965, Vol. 14, no 11 Pt 1, p. 2563-2568Article in journal (Refereed)
  • 1266. Xun, Wei Wei
    et al.
    Brennan, Paul
    Tjonneland, Anne
    Vogel, Ulla
    Overvad, Kim
    Kaaks, Rudolf
    Canzian, Federico
    Boeing, Heiner
    Trichopoulou, Antonia
    Oustoglou, Erifili
    Giotaki, Zoi
    Johansson, Mattias
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H M
    Lund, Eiliv
    Kumle, Merethe
    Rodríguez, Laudina
    Agudo, Antonio
    Sánchez, Maria-José
    Arriola, Larraitz
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Key, Tim
    Riboli, Elio
    Vineis, Paolo
    Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC).2011In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 26, no 5, p. 657-666Article in journal (Refereed)
    Abstract [en]

    The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

  • 1267. Yi, W
    et al.
    Haapasalo, H
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Järvelä, S
    Raheem, O
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age2009In: Clinical Neuropathology, ISSN 0722-5091, Vol. 28, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Three human leucine-rich repeats and immunoglobulin-like domains (LRIG1-3) genes and proteins have recently been characterized. LRIG1 has been shown to be a suppressor of tumor growth by counteracting the signaling of epidermal growth factor receptor (EGFR) family members, including EGFR (ERBB1). Expression of LRIG proteins seems to be of importance in the pathogenesis of astrocytic tumors. In this study, the expression of LRIG1-3 was evaluated in 51 human ependymomas by immunohistochemistry. LRIG proteins were detected in all ependymomas analyzed, however, with a pronounced heterogeneity in expression and subcellular localization. Higher cytoplasmic immunoreactivity of LRIG1 correlated with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO Grade. LRIG1 displayed a stronger immunoreactivity in the cytoplasm and nuclei in spinal ependymomas than in the posterior fossa or supratentorial ependymomas, while perinuclear LRIG3 was more highly expressed in supratentorial than in infratentorial ependymomas. The indications that expression and subcellular localization of LRIG proteins could be pathogenetically associated with specific clinicopathological features of ependymoma tumors might be of importance in the carcinogeneses and tumor progression of human ependymomas.

  • 1268.
    Yi, Wei
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Inui, Shigeki
    Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Japan.
    Lei, Ting
    Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
    Itami, Satoshi
    Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Japan.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 12011In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 317, no 4, p. 504-512Article in journal (Refereed)
    Abstract [en]

    Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a recently discovered negative regulator of growth factor signaling. The LRIG1 integral membrane protein has been demonstrated to regulate various oncogenic receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR), by cell-autonomous mechanisms. Here, we investigated whether LRIG1 ectodomains were shed, and if LRIG1 could regulate cell proliferation and EGF signaling in a paracrine manner. Cells constitutively shed LRIG1 ectodomains in vitro, and shedding was modulated by known regulators of metalloproteases, including the ADAM17 specific inhibitor TAPI-2. Furthermore, shedding was enhanced by ectopic expression of Adam17. LRIG1 ectodomains appeared to be shed in vivo, as well, as demonstrated by immunoblotting of mouse and human tissue lysates. Ectopic expression of LRIG1 in lymphocytes suppressed EGF signaling in co-cultured fibroblastoid cells, demonstrating that shed LRIG1 ectodomains can function in a paracrine fashion. Purified LRIG1 ectodomains suppressed EGF signaling without any apparent downregulation of EGFR levels. Taken together, the results show that the LRIG1 ectodomain can be proteolytically shed and can function as a non-cell-autonomous regulator of growth factor signaling. Thus, LRIG1 or its ectodomain could have therapeutic potential in the treatment of growth factor receptor-dependent cancers.

  • 1269.
    Zackrisson, B
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Arevarn, M
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Optimized MLC-beam arrangements for tangential breast irradiation2000In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 54, no 3, p. 209-212Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Very large numbers of women are treated with tangential breast irradiation after breast-conserving surgery due to mammary carcinoma. The aim of this study was to improve a conventional treatment plan by modifying the dose intensity in the beams to reduce the absorbed dose outside the planning target volume (PTV) and to reduce the absorbed dose variation inside the PTV diotherapy of mammary carcinoma. Materials and methods: Treatment planning was performed both with conventional technique and with a simple intensity modulation technique for 12 consecutive patients. Results: In all cases a higher degree of dose conformity was obtained with the dose intensity modulation technique. The relative gain was found to be similar for all patients irrespective of the size of the target volume or the irradiated lung volume. Conclusion: Simple manual intensify modulation can be used to improve the dose distribution in tangential breast irradiation. With modern accelerators the increased time for this technique is less than 2 min per fraction. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

  • 1270.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Matching of electron beams for conformal therapy of target volumes at moderate depths1996In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 39, no 3, p. 261-270Article in journal (Refereed)
    Abstract [en]

    The basic requirements for conformal electron therapy are an accelerator with a wide range of energies and field shapes. The beams should be well characterised in a full 3-D dose planning system which has been verified for the geometries of the current application. Differences in the basic design of treatment units have been shown to have a large influence on beam quality and dosimetry. Modern equipment can deliver electron beams of good quality with a high degree of accuracy. A race-track microtron with minimised electron scattering and a multi-leaf collimator (MLC) for electron collimating will facilitate the isocentric technique as a general treatment technique for electrons. This will improve the possibility of performing combined electron field techniques in order to conform the dose distribution with no or minimal use of a bolus. Furthermore, the isocentric technique will facilitate multiple field arrangements that decrease the problems with distortion of the dose distribution due to inhomogeneities, etc. These situations are demonstrated by clinical examples where isocentric, matched electron fields for treatment of the nose, thyroid and thoracic wall have been used.

  • 1271.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brun, Eva
    Nyman, Jan
    Friesland, Signe
    Reizenstein, Johan
    Sjodin, Helena
    Ekberg, Lars
    Lödén, Britta
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ask, Anders
    Wickart-Johansson, Gun
    Lewin, Freddi
    Björk-Eriksson, Thomas
    Lundin, Erik
    Dalianis, Tina
    Wennerberg, Johan
    Johansson, Karl-Axel
    Nilsson, Per
    Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial2015In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 117, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

    Background and purpose: This report contains the mature five-year data from the Swedish ARTSCAN trial including information on the influence of p16 positivity (p16+) for oropharyngeal cancers. Material and methods: Patients with previously untreated squamous cell carcinoma without distant metastases of the oral cavity, oropharynx, larynx (except T1-2, NO glottic cancers) and hypopharynx were included. Patients were randomised between accelerated fractionation (AF) (1.1 Gy + 2 Gy per day, 5 days/week for 4.5 weeks, total dose 68 Gy) and conventional fractionation (CF) (2 Gy per day, 5 days/week for 7 weeks, total dose 68 Gy). Human papillomavirus (HPV)-associated p16-expression was assessed retrospectively in tumour tissues from patients with oropharyngeal carcinoma. Results: There was no significant difference in loco-regional control (LRC) between AF and CF (log-rank test p = 0.75). LRC at 5 years was 65.5% for AF and 64.9% for CF. Overall survival (OS) was similar in both arms (p = 0.99). The estimated cancer specific survival (CSS) at 5 years was 62.2% (AF) and 63.3% (CF) (p = 0.99). 206 specimens were analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients with p16+ tumours had a statistically significant better overall prognosis compared with p16 tumours. Conclusion: This update confirms the results of the 2-year report. We failed to identify a positive effect resulting from AF with regards to LRC, OS and CSS. The addition of information on the HPV-associated p16 overexpression did not explain this lack of effect.

  • 1272.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Kjellén, Elisabeth
    Skåne University Hospital, Lund and Malmö, Sweden.
    Johansson, Karl-Axel
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Modig, Hans
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brun, Eva
    Skåne University Hospital, Lund and Malmö, Sweden.
    Nyman, Jan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Friesland, Signe
    Karolinska University Hospital, Stockholm, Sweden.
    Reizenstein, Johan
    Örebro University Hospital, Örebro, Sweden.
    Sjödin, Helena
    Karolinska University Hospital, Stockholm, Sweden.
    Ekberg, Lars
    Skåne University Hospital, Lund and Malmö, Sweden.
    Lödén, Britta
    Karlstad Central Hospital, Karlstad, Sweden.
    Mercke, Claes
    Karolinska University Hospital, Stockholm, Sweden.
    Fernberg, Jan-Olof
    Karolinska University Hospital, Stockholm, Sweden.
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ask, Anders
    Skåne University Hospital, Lund and Malmö, Sweden.
    Persson, Essie
    Örebro University Hospital, Örebro, Sweden.
    Wickart-Johansson, Gun
    Karolinska University Hospital, Stockholm, Sweden.
    Lewin, Freddi
    Karolinska University Hospital, Stockholm, Sweden.
    Wittgren, Lena
    Skåne University Hospital, Lund and Malmö, Sweden.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björk-Eriksson, Thomas
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN study2011In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 100, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Studies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF.

    Materials and methods: Patients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1-T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. RESULTS: The study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III-IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3-T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects.

    Conclusion: Overall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.

     

  • 1273. Zakeri, K.
    et al.
    Rotolo, F.
    Lacas, B.
    Vitzthum, L. K.
    Le, Q-TX.
    Gregoire, V.
    Overgaard, J.
    Tobias, J.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Parmar, M. K.
    Burtness, B. A.
    Ghi, M. G.
    Sanguineti, G.
    O'Sullivan, B.
    Fortpied, C.
    Bourhis, J.
    Shen, H.
    Harris, J.
    Pignon, J-P
    Mell, L. K.
    Predictor of effectiveness of treatment intensification on overall survival in head and neck cancer (HNC)2018In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29Article in journal (Other academic)
  • 1274. Zamora-Ros, Raul
    et al.
    Alghamdi, Muath A.
    Cayssials, Valerie
    Franceschi, Silvia
    Almquist, Martin
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Hammer Bech, Bodil
    Overvad, Kim
    Tjonneland, Anne
    Petersen, Kristina E. N.
    Mancini, Francesca Romana
    Mahamat-Saleh, Yahya
    Bonnet, Fabrice
    Kuehn, Tilman
    Fortner, Renee T.
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Martimianaki, Georgia
    Masala, Giovanna
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Fasanelli, Francesca
    Skeie, Guri
    Braaten, Tonje
    Lasheras, Cristina
    Salamanca-Fernandez, Elena
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Manjer, Jonas
    Wallstrom, Peter
    Bueno-de-Mesquita, H. Bas
    Peeters, Petra H.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Schmidt, Julie A.
    Aune, Dagfinn
    Byrnes, Graham
    Scalbert, Augustin
    Agudo, Antonio
    Rinaldi, Sabina
    Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study2019In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 58, no 8, p. 3303-3312Article in journal (Refereed)
    Abstract [en]

    Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study.

    Methods: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires.

    Results: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97–1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95–1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95–1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81–0.99), but this association was based on a sub-analysis with a small number of cancer cases.

    Conclusions: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

  • 1275. Zamora-Ros, Raul
    et al.
    Barupal, Dinesh K.
    Rothwell, Joseph A.
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Aleksandrova, Krasimira
    Overvad, Kim
    Kyro, Cecilie
    Tjonneland, Anne
    Affret, Aurelie
    His, Mathilde
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Kuehn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Naska, Androniki
    Kritikou, Maria
    Saieva, Calogero
    Agnoli, Claudia
    de Magistris, Maria Santucci
    Tumino, Rosario
    Fasanelli, Francesca
    Weiderpass, Elisabete
    Skeie, Guri
    Merino, Susana
    Jakszyn, Paula
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Navarro, Carmen
    Ardanaz, Eva
    Sonestedt, Emily
    Ericson, Ulrika
    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.
    Bodén, Stina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Perez-Cornago, Aurora
    Wareham, Nicholas J.
    Khaw, Kay-Thee
    Freisling, Heinz
    Cross, Amanda J.
    Riboli, Elio
    Scalbert, Augustin
    Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 8, p. 1836-1844Article in journal (Refereed)
    Abstract [en]

    Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.

  • 1276. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Biessy, Carine
    Tjonneland, Anne
    Halkjaer, Jytte
    Fournier, Agnes
    Boutron-Ruault, Marie-Christine
    Mesrine, Sylvie
    Tikk, Kaja
    Fortner, Renee T.
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Papatesta, Eleni-Maria
    Masala, Giovanna
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Polidoro, Silvia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Weiderpass, Elisabete
    Lund, Eiliv
    Argueelles, Marcial
    Agudo, Antonio
    Molina-Montes, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Larranaga, Nerea
    Manjer, Jonas
    Almquist, Martin
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tsilidis, Konstantinos K.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Romieu, Isabelle
    Byrnes, Graham
    Gunter, Marc J.
    Riboli, Elio
    Franceschi, Silvia
    Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 5, p. 1218-1227Article in journal (Refereed)
    Abstract [en]

    Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for 9 vs. 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR=1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR=1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.

  • 1277. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Rostgaard-Hansen, Agnetha Linn
    Tjonneland, Anne
    Clavel-Chapelon, Francoise
    Mesrine, Sylvie
    Katzke, Verena A.
    Kuehn, Tilman
    Foerster, Jana
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Klinaki, Eleni
    Masala, Giovanna
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Mattiello, Amalia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Engeset, Dagrun
    Skeie, Guri
    Argueelles, Marcial
    Agudo, Antonio
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Chamosa, Saioa
    Almquist, Martin
    Tosovic, Ada
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Cross, Amanda J.
    Slimani, Nadia
    Byrnes, Graham
    Romieu, Isabelle
    Riboli, Elio
    Franceschi, Silvia
    Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

    Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4vs.Q1, 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4vs.Q1, 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI25 and with sugar intake in those with BMI<25. Moreover, inverse associations with starch and GI were observed in subjects with BMI<25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people. What's New? The role of lifestyle factors in the growing numbers of thyroid cancer remains unclear. Here, the authors uncover associations with high total energy intake and low consumption of polyunsaturated fatty acids in a large European cohort (EPIC). They further find positive associations with starch intake and glycemic index only in people with a body mass index equal or larger than 25, possibly implicating an altered insulin response in the etiology of this cancer.

  • 1278.
    Zborayova, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Blomqvist, L.
    Flygare, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Gebre-Medhin, M.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Söderkvist, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Early changes in multiparametric imaging parameters during radiotherapy of squamous carcinoma2019In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 132, p. 63-63Article in journal (Other academic)
  • 1279. Zein, Nabila
    et al.
    Aziz, Safa W.
    El-Sayed, Ashraf S.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Comparative cytotoxic and anticancer effect of Taxol derived from Aspergillus terreus and Taxus brevifolia2019In: Bioscience Research, ISSN 1811-9506, E-ISSN 2218-3973, Vol. 16, no 2, p. 1500-1509Article in journal (Refereed)
    Abstract [en]

    Taxol is a highly oxygenated diterpenoid of broad spectrum anticancer activity, due it unique specificity for binding with tubulin beta-subunits heterodimer of tumor cells, disrupting their mitotic division. Taxol has been commercially produced from Taxus brevifolia, however, its lower yield, accessibility and pricey are the current challenges for this technology, thus, exploring of fungi as alternative source of Taxol could opened new platforms for production of this drug. From our previous studies, Taxol has been produced by A. terreus with the same chemical structural identity with that from T. brevifolia. Thus, the objective of this study was to comparatively evaluate the cytotoxicity and anticancer activity of Aspergillus terreus Taxol (AT-Taxol) and commercial Taxus brevifolia Taxol (TB-Taxol) against Ehrlich ascites carcinoma in female Swiss albino mice via intraperitoneal injection. Taxol from both sources had the same cytotoxic biochemical patterns, as well as anticancer activity against Ehrlich ascites carcinoma. Positive control mice showed an increasing on the serum nitric oxide (NO) and lipid peroxidation (MDA) level accompanied by a decline in total antioxidant capacity (TAC) in addition to MMP9 upregulation and caspase-3 down regulation. Histopathologically, liver and kidney tissues showed some pathological features due to the oxidative stress induced by EAC. AT-Taxol and TB-Taxol gave the same potent antioxidant and anticancer properties by augmenting the antioxidant defense system through induction of apoptosis and protecting both liver and kidney against oxidative stress induced by Ehrlich ascites carcinoma.

  • 1280. Zeleniuch-Jacquotte, A
    et al.
    Shore, R E
    Afanasyeva, Y
    Lukanova, A
    Sieri, S
    Koenig, K L
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Krogh, V
    Liu, M
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Muti, P
    Arslan, A A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, P
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 9, p. 1458-1464Article in journal (Refereed)
    Abstract [en]

    Background: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.

    Methods: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.

    Results: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.

    Conclusion: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

  • 1281. Zeleniuch-Jacquotte, Anne
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Micheli, Andrea
    Koenig, Karen L
    Lenner, Per
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Muti, Paola
    Shore, Roy E
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Krogh, Vittorio
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Afanasyeva, Yelena
    Rinaldi, Sabina
    Arslan, Alan A
    Kaaks, Rudolf
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Adlercreutz, Herman
    Circulating enterolactone and risk of endometrial cancer2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, no 10, p. 2376-2381Article in journal (Refereed)
    Abstract [en]

    It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.

  • 1282. Zhao, Hongjuan
    et al.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Tibshirani, Robert
    Brooks, James D
    Gene expression profiling predicts survival in conventional renal cell carcinoma2006In: PLoS Med, ISSN 1549-1676, Vol. 3, no 1, p. e13-Article in journal (Refereed)
  • 1283. Zheng, S Lilly
    et al.
    Augustsson-Bälter, Katarina
    Chang, Baoli
    Hedelin, Maria
    Li, Liwu
    Adami, Hans-Olov
    Bensen, Jeanette
    Li, Ge
    Johnasson, Jan-Erik
    Turner, Aubrey R
    Adams, Tamara S
    Meyers, Deborah A
    Isaacs, William B
    Xu, Jianfeng
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the CAncer Prostate in Sweden Study2004In: Cancer Res, ISSN 0008-5472, Vol. 64, no 8, p. 2918-2922Article in journal (Refereed)
  • 1284. Zheng, S Lilly
    et al.
    Liu, Wennuan
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Dimitrov, Latchezar
    Bälter, Katarina
    Sun, Jielin
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Sun, Jishan
    Chang, Baoli
    Loza, Matthew
    Turner, Aubrey R
    Bleecker, Eugene R
    Meyers, Deborah A
    Carpten, John D
    Duggan, David
    Isaacs, William B
    Xu, Jianfeng
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    A comprehensive association study for genes in inflammation pathway provides support for their roles in prostate cancer risk in the CAPS study2006In: Prostate, ISSN 0270-4137, Vol. 66, no 14, p. 1556-1564Article in journal (Refereed)
  • 1285. Zuo, H.
    et al.
    Ueland, P. M.
    Midttun, O.
    Tell, G. S.
    Fanidi, A.
    Zheng, W.
    Shu, X.
    Xiang, Y.
    Wu, J.
    Prentice, R.
    Pettinger, M.
    Thomson, C. A.
    Giles, G. G.
    Hodge, A.
    Cai, Q.
    Blot, W. J.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stevens, V. L.
    McCullough, M. L.
    Weinstein, S. J.
    Albanes, D.
    Ziegler, R. G.
    Freedman, N. D.
    Caporaso, N. E.
    Langhammer, A.
    Hveem, K.
    Naess, M.
    Buring, J. E.
    Lee, I.
    Gaziano, J. M.
    Severi, G.
    Zhang, X.
    Stampfer, M. J.
    Han, J.
    Zeleniuch-Jacquotte, A.
    Marchand, L. L.
    Yuan, J.
    Wang, R.
    Koh, W.
    Gao, Y.
    Ericson, U.
    Visvanathan, K.
    Jones, M. R.
    Relton, C.
    Brennan, P.
    Ulvik, A.
    Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3)2019In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 30, no 3, p. 478-485Article in journal (Refereed)
    Abstract [en]

    Background: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known.

    Materials and methods: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models.

    Results: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3years of blood draw (OR: 1.73, 95% CI: 1.34-2.23).

    Conclusion: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

  • 1286. Årstrand, K
    et al.
    Kullman, A
    Andersson, Ronny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Kågedal, B
    Improved method for analysis of cysteinyldopa in human serum2004In: Scand J Clin Lab Invest, ISSN 0036-5513, Vol. 64, no 6, p. 559-564Article in journal (Refereed)
  • 1287.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Höyhtyä, Matti
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lindmark, Gudrun
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer2000In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, no 2B, p. 1085-1091Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We studied whether preoperative serum levels of free MMP-2, the MMP-2/TIMP-2 complex, and total amounts of MMP-9, TIMP-1 and TIMP-2 correlated to the tumor stage and prognosis in colorectal cancer.

    METHODS: Samples from 158 patients operated on for colorectal cancer (100 colon, 58 rectum) and samples from 80 healthy blood donors were analyzed using an ELISA technique. One hundred and thirty-three patients were resected for cure, (31, 61, and 41 in Dukes' stages A, B, and C, respectively). At follow-up in January 1998, 44 patients had died from their cancer after a median time 14 months (range 2-55). Fifteen patients died without tumor relapse. Ninety-nine patients were alive after, a median time of 46 months (range 17-68).

    RESULTS: Wide, overlapping ranges were observed for all factors both in the patients and in the control group. The patients as compared to the control group had significantly higher levels of free MMP-2 and total amounts of MMP-9, TIMP-1 and TIMP-2, whereas the level of the MMP-2/TIMP-2 complex was significantly lower. TIMP-1 was significantly higher in Dukes' D compared to Dukes' A-C cases; the other factors did not correlate to tumor stage. Elevated TIMP-2 levels (median cut-off limit), only, correlated to worse prognosis when analysed in all patients (p < 0.05). None of the factors (median cut-off limit) correlated to survival in Dukes' A-C patients; analyses based on the upper quartile cut-off limit demonstrated that elevated MMP-2 levels correlated to shorter survival time (p < 0.05).

    CONCLUSION: Serum analyses of free MMP-2 the MMP-2/TIMP-2 complex and total amounts of MMP-9, TIMP-1 and TIMP-2 are of limited value for tumor staging and prognosis in colorectal cancer.

  • 1288.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindmark, Gudrun
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Are lymph node micrometastases of any clinical significance in Dukes' stages A and B colorectal cancer?1998In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 41, no 10, p. 1244-1249Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer.

    METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody.

    RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases.

    CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.

  • 1289.
    Öhman, Andreas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Is visual assessment of breast density reliable in mammographic screening?2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 1290.
    Öster, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hedestig, Oliver
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mona
    Umeå University, Faculty of Medicine, Department of Nursing.
    Klingstedt, Nina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sharing experiences in a support group: men's talk during the radiotherapy period for prostate cancer2013In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 11, no 4, p. 331-339Article in journal (Refereed)
    Abstract [en]

    Objective: Prostate cancer, one of the most common cancers in men, is often treated with radiotherapy, which strains both physical and mental health. This study aimed to describe the experiences of men living with prostate cancer shared within conversational support groups during a course of radiotherapy. Method: Nine men participated in one of two groups that met six or seven times, led by a professional nurse. Qualitative content analysis was used to identify themes and subthemes in the recorded group conversations. Results: The analysis resulted in six themes: living with a changing body, being in the hands of others, learning to live with the disease, the importance of knowledge, everyday life support, and meeting in the support group. The men discussed a wide variety of bodily experiences and described support from healthcare professionals, relatives, friends, and the support group as crucial to their recovery. Significance of results: Meeting men in a similar situation, sharing experiences of living with the disease, and feeling allied to each other were important to the men in our study. The conversational support group provided the patient with prostate cancer a forum where sharing was made possible.

  • 1291.
    Öster, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Edberg Thyme, Karin
    Magnusson, Eva
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Åström, Sture
    Umeå University, Faculty of Medicine, Department of Nursing.
    Art therapy during radiotherapy – A five-year follow-up study with women diagnosed with breast cancer2014In: The arts in psychotherapy, ISSN 0197-4556, E-ISSN 1873-5878, Vol. 41, no 1, p. 36-40Article in journal (Refereed)
    Abstract [en]

    Follow-up studies on art therapy are lacking. In a randomised art therapy intervention study from 2001 to 2004 with women with breast cancer, results showed that patients benefitted from participating in art therapy for up to four months after the intervention. The aim of this study was to describe the coping resources and quality of life amongst women treated for breast cancer five to seven years after participating in individual art therapy during radiotherapy as compared to a control group. In 2009, thirty-seven women, 18 from the intervention group and 19 from the control group, answered questionnaires about their coping resources and quality of life. The results showed no significant difference between the groups regarding their coping resources or quality of life, except for an unexpected significantly lower score in the domain 'Social relations' in the study group as compared to baseline, at the time of the follow up. However, our study from 2001 to 2004 supports various positive effects of art therapy within six months of participation as compared to a control group. Consequently, attending art therapy during the treatment period for breast cancer can be of great importance to support health, coping and quality of life in a short-term perspective.

  • 1292.
    Öster, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Egberg Thyme, Karin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Magnusson, Eva
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Åström, Sture
    Umeå University, Faculty of Medicine, Department of Nursing.
    Art therapy during radiotherapy: a five-year follow-up study with women diagnosed with breast cancer2014In: The arts in psychotherapy, ISSN 0197-4556, E-ISSN 1873-5878, Vol. 41, no 1, p. 36-40Article in journal (Refereed)
    Abstract [en]

    Follow-up studies on art therapy are lacking. In a randomised art therapy intervention study from 2001-2004 with women with breast cancer, results showed that patients benefitted from participating in art therapy for up to at least four months after the intervention. The aim of this study was to describe the coping resources and quality of life amongst women treated for breast cancer five - seven years after participating in individual art therapy during radiotherapy as compared to a control group. In 2009, thirty-seven women, 18 from the intervention group and 19 from the control group, answered questionnaires about their coping resources and quality of life. The results showed no significant difference between the groups regarding their coping resources or quality of life, except for an unexpected significantly lower score in the domain ‘Social relations’ in the study group as compared to baseline, at the time of the follow up. However, our study from 2001–2004 supports various positive effects of art therapy within six months of participation as compared to a control group. Consequently, attending art therapy during the treatment period for breast cancer can be of great importance to support health, coping and quality of life in a short-term perspective.

  • 1293.
    Öster, Inger
    et al.
    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.
    Magnusson, Eva
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Women with breast cancer and gendered limits and boundaries: Art therapy as a safe space for enacting alternative subject positions2009In: The arts in psychotherapy, ISSN 0197-4556, E-ISSN 1873-5878, Vol. 36, no 1, p. 29-38Article in journal (Refereed)
    Abstract [en]

    This article takes its starting point from certain results from our randomized study on art therapy with women with breast cancer. Previous results from this study showed significant benefits on coping, quality of life, and symptoms for women who participated in an art therapy intervention. Analyses of interviews and diaries showed that especially women from the intervention group had distanced themselves from traditionally gendered understandings about cultural limits and boundaries. The aim of this study was to gain further knowledge about how women with breast cancer who participated in the art therapy intervention gave meaning to the gendered limits and boundaries in their daily lives, and to trace their trajectories, in therapy, towards helpful management of restraining boundaries. When analyzing the women's verbal reflections on the therapy sessions, we discerned five subject positions, defining them as follows: being someone who reacts to violation attempts; actively connecting body and self; actively locating oneself and moving forward; being in a position to see important connections throughout life; and being able to acknowledge and harbour conflicting emotions. The results of the study suggest that art therapy served as a tool that helped the women to get access to subject positions that enabled them to protect and strengthen their boundaries. This involved challenging dominating discourses and reacting against perceived boundary violations. Art therapy offered a personal, physical, and pictorial “safe space” with opportunities to deal with complex existential experiences and issues, and also make important connections throughout life. Looking back and summarizing important experiences acted as a way to prepare oneself for the future and moving forward.

  • 1294. Österborg, Anders
    et al.
    Brandberg, Yvonne
    Hedenus, Michael
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Impact of epoetin-beta on survival of patients with lymphoproliferative malignancies: long-term follow up of a large randomized study2005In: Br J Haematol, ISSN 0007-1048, Vol. 129, no 2, p. 206-209Article in journal (Refereed)
23242526 1251 - 1294 of 1294
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