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  • 101.
    Best, Myron
    et al.
    VU Medical Center, Amsterdam, Netherlands.
    Sol, Nik
    VU Medical Center, Amsterdam, Netherlands.
    Kooi, Irsan
    VU Medical Center, Amsterdam, Netherlands.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Westerman, Bart
    VU Medical Center, Amsterdam, Netherlands.
    Yistra, Bauke
    VU Medical Center, Amsterdam, Netherlands.
    Dorsman, Josephine
    VU Medical Center, Amsterdam, Netherlands.
    Smit, Egbert
    VU Medical Center, Amsterdam, Netherlands.
    Verheui, Henk
    VU Medical Center, Amsterdam, Netherlands.
    Reijneveld, Jaap
    VU Medical Center, Amsterdam, Netherlands.
    Tannous, Bakhos
    Massachusetts General Hospital, Boston, MA, USA.
    Wesseling, Pieter
    VU Medical Center, Amsterdam, Netherlands.
    Wurdinger, Thomas
    VU Medical Center, Amsterdam, Netherlands.
    Tumor-educated platelets allow for multiclass liquid biopsy-based diagnosis of cancer2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no Suppl. 15, article id LB-124Article in journal (Other academic)
  • 102. Best, Myron
    et al.
    Sol, Nik
    Kooi, Irsan
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Westerman, Bart
    Ylstra, Bauke
    Dorsman, Josephine
    Smit, Egbert F
    Verheul, Henk M W
    Reijneveld, Jaap C
    Tannous, Bakhos A
    Wesseling, Pieter
    Wurdinger, Thomas
    Allowance of tumor-educated platelets for multiclass liquid biopsy-based diagnosis of cancer2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15, suppl., article id 11058Article in journal (Other academic)
  • 103. Bethke, Lara
    et al.
    Murray, Anne
    Webb, Emily
    Schoemaker, Minouk
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Kosteljanetz, Michael
    Swerdlow, Anthony
    Houlston, Richard
    Comprehensive analysis of DNA repair gene variants and risk of meningioma2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 4, p. 270-276Article in journal (Refereed)
    Abstract [en]

    Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility.

    Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case–control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided.

    Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1–interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 × 10−6; P = .009 after adjusting for multiple testing).

    Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.

  • 104. Bethke, Lara
    et al.
    Sullivan, Kate
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Swerdlow, Anthony
    Houlston, Richard
    CASP8 D302H and meningioma risk: an analysis of five case-control series2009In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 273, no 2, p. 312-315Article in journal (Refereed)
    Abstract [en]

    Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.

  • 105. Bethke, Lara
    et al.
    Sullivan, Kate
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Swerdlow, Anthony
    Houlston, Richard
    The Common D302H Variant of CASP8 Is Associated with Risk of Glioma2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 4, p. 987-989Article in journal (Refereed)
    Abstract [en]

    Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.

  • 106. Bethke, Lara
    et al.
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Swerdlow, Anthony
    Houlston, Richard
    Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 5, p. 1195-1202Article in journal (Refereed)
    Abstract [en]

    Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.

  • 107. Bethke, Lara
    et al.
    Webb, Emily
    Murray, Anne
    Schoemaker, Minouk
    Johansen, Christoffer
    Collatz Christensen, Helle
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Swerdlow, Anthony
    Houlston, Richard
    Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma2008In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 17, no 6, p. 800-805Article in journal (Refereed)
    Abstract [en]

    Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case–control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case–control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14–1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.

  • 108.
    Bhattacharjee, Samsiddhi
    et al.
    Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, Maryland 20852, USA.
    Rajaraman, Preetha
    Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, Maryland 20852, USA.
    Jacobs, Kevin B
    Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 8717 Grovemont Circle, Gaithersburg, Maryland 20877, USA.
    Wheeler, William A
    Information Management Services, Rockville, MD 20852, USA.
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hartge, Patricia
    Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
    GliomaScan Consortium,
    GliomaScan Consortium investigators and affiliations are available in the Supplemental Data.
    Yeager, Meredith
    Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 8717 Grovemont Circle, Gaithersburg, Maryland 20877, USA.
    Chung, Charles C
    Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
    Chanock, Stephen J
    Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
    Chatterjee, Nilanjan
    Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Rockville, Maryland 20852, USA.
    A subset-based approach improves power and interpretation for the combined analysis of genetic association studies of heterogeneous traits2012In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 90, no 5, p. 821-835Article in journal (Refereed)
    Abstract [en]

    Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical approaches for meta-analysis or pooled analysis, however, might not be suitable for such analysis because individual variants are likely to be associated with only a subset of the traits or might demonstrate effects in different directions. We propose a method that exhaustively explores subsets of studies for the presence of true association signals that are in either the same direction or possibly opposite directions. An efficient approximation is used for rapid evaluation of p values. We present two illustrative applications, one for a meta-analysis of separate case-control studies of six distinct cancers and another for pooled analysis of a case-control study of glioma, a class of brain tumors that contains heterogeneous subtypes. Both the applications and additional simulation studies demonstrate that the proposed methods offer improved power and more interpretable results when compared to traditional methods for the analysis of heterogeneous traits. The proposed framework has applications beyond genetic association studies.

  • 109. Bijnsdorp, Irene V.
    et al.
    Hodzic, Jasmina
    Lagerweij, Tonny
    Westerman, Bart
    Krijgsman, Oscar
    Broeke, Jurjen
    Verweij, Frederik
    Nilsson, R. Jonas A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Department of Neurosurgery, VU University Medical Center, Amsterdam, The Netherlands.
    Rozendaal, Lawrence
    van Beusechem, Victor W.
    van Moorselaar, Jeroen A.
    Wurdinger, Thomas
    Geldof, Albert A.
    miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP1102016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 13, p. 16676-16687Article in journal (Refereed)
    Abstract [en]

    The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.

  • 110. Bisschop, Charlotte N. Steins
    et al.
    van Gils, Carla H.
    Emaus, Marleen J.
    Bueno-de-Mesquita, H. Bas
    Monninkhof, Evelyn M.
    Boeing, Heiner
    Aleksandrova, Krasmira
    Jenab, Mazda
    Norat, Teresa
    Riboli, Elio
    Boutron-Rualt, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Naccarati, Alessio
    Mattiello, Amalia
    Vicente Argueeles, Marcial
    Jose Sanchez, Maria
    Jose Tormo, Maria
    Ardanaz, Eva
    Dorronsoro, Miren
    Bonet, Catalina
    Khaw, Kay-Tee
    Key, Tim
    Trichopoulou, Antonia
    Orfanos, Philippos
    Naska, Androniki
    Kaaks, Rudolph R.
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pischon, Tobias
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jirstrom, Karin
    Ohlsson, Bodil
    Overvad, Kim
    Berentzen, Tina Landsvig
    Halkjaer, Jytte
    Tjonneland, Anne
    Weiderpass, Elisabete
    Skeie, Guri
    Braaten, Tonje
    Siersema, Peter D.
    Freisling, Heinz
    Ferrari, Pietro
    Peeters, Petra H. M.
    May, Anne M.
    Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study2014In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, no 1, p. 139-147Article in journal (Refereed)
    Abstract [en]

    Background: A moderate association exists between body mass index (BMI) and colorectal cancer. Less is known about the effect of weight change. Objective: We investigated the relation between BMI and weight change and subsequent colon and rectal cancer risk. Design: This was studied among 328,781 participants in the prospective European Prospective Investigation into Cancer Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating study (mean age: 50 y). Body weight was assessed at recruitment and on average 5 y later. Self-reported weight change (kg/y) was categorized in sex-specific quintiles, with quintiles 2 and 3 combined as the reference category (men: -0.6 to 0.3 kg/y; women: -0.4 to 0.4 kg/y). In the subsequent years, participants were followed for the occurrence of colon and rectal cancer (median period: 6.8 y). Multivariable Cox proportional hazards regression analyses were used to study the association. Results: A total of 1261 incident colon cancer and 747 rectal cancer cases were identified. ME at recruitment was statistically significantly associated with colon cancer risk in men (HR: 1.04; 95% CI: 1.02, 1.07). Moderate weight gain (quintile 4) in men increased risk further (HR: 1.32; 95% CI: 1.04, 1.68), but this relation did not show a clear trend. In women, BMI or weight gain was not related to subsequent risk of colon cancer. No statistically significant associations for weight loss and colon cancer or for BMI and weight changes and rectal cancer were found. Conclusions: BMI attained at adulthood was associated with colon cancer risk. Subsequent weight gain or loss was not related to colon or rectal cancer risk in men or women.

  • 111. Bjerkvig, Rolf
    et al.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. NorLux Neuro-Oncology Laboratory, Centre de Recherche Public Santé, 84, Val Fleuri, L-1526 Luxembourg.
    Miletic, Hrvoje
    Niclou, Simone P
    Cancer stem cells and angiogenesis2009In: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 19, no 5, p. 279-284Article, review/survey (Refereed)
    Abstract [en]

    Most cancers contain tumor cells that display stem cell-like characteristics. How and when such cells appear in tumors are not clear, but may involve both stochastic as well as hierarchical events Most. likely, tumor cells that display stem cell-like characteristics can undergo asymmetric cell division giving rise to tumor cells that trigger angiogenic programs. As normal stem cells the cancer stem-like cells seem to adapt to hypoxic environments and will use metabolic pathways that involve increased conversion of glucose to pyruvate and lactate, and a concomitant decrease in mitochondrial metabolism and mitochondrial mass. The molecular pathways responsible for inducing glycolysis are now being explored. These pathways seem to mediate multiple metabolic functions in cancer stem-like cells, leading to a highly migratory and angiogenesis-independent phenotype. Future challenges will be to identify and validate molecular targets involved in anaerobic metabolic pathways active in cancer stem-like cells and to determine how these pathways differ from regulatory pathways involved in normal stem cell function.

  • 112.
    Björ, Bodil
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Burström, Lage
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nathanaelsson, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Fifty-year-follow-up of mortality among a cohort of iron-ore miners in Sweden, with specific reference to myocardial infarction mortality2009In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 66, no 4, p. 264-268Article in journal (Refereed)
    Abstract [en]

    Objectives: This study investigates both general mortality and mortality from myocardial infarction among men employed in iron-ore mines in Sweden.

    Methods: The mortality of employees (surface and underground workers) at the iron-ore mines in Malmberget and Kiruna, Sweden was investigated. The study cohort comprised men who had been employed for at least 1 year between 1923 and 1996. The causes of death were obtained from the national cause of death register from 1952 to 2001. Indirect standardised mortality ratios (SMR) were calculated for four main causes. Mortality specifically from myocardial infarction was also analysed.

    Results: 4504 deaths in the cohort gave an SMR for total mortality of 1.05 (95% CI 1.02 to 1.09). Mortality was significantly higher for lung cancer (SMR 1.73, 95% CI 1.52 to 1.97). There was an increased risk of injuries and poisonings (SMR 1.34, 95% CI 1.24 to 1.46) and respiratory diseases (SMR 1.14, 95% CI 1.00 to 1.28). There were 1477 cases of myocardial infarction, resulting in an SMR of 1.12 (95% CI 1.07 to 1.18). SMR was higher (1.35, 95% CI 1.22 to 1.50) for men aged ≤60 years than for those >60 years of age (1.06, 95% CI 1.00 to 1.13).

    Conclusions: Mortality from myocardial infarction was higher than expected. There was also an increased risk of death from injuries and poisonings, lung cancer and respiratory diseases, as well as higher general mortality. Our findings support the results of previous studies that there is an association between working in the mining industry and adverse health outcomes.

  • 113.
    Björ, Bodil M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Burström, Lage
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nathanaelsson, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Tohr K F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Mortality from myocardial infarction in relation to exposure to vibration and dust among a cohort of iron-ore miners in Sweden2010In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 67, no 3, p. 154-158Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to investigate myocardial infarction mortality in relation to exposure to hand-arm vibration (HAV) and whole-body vibration (WBW) as well as exposure to dust among men employed in two Swedish iron-ore mines. METHODS: This study comprised employed men at two iron-ore mines in Sweden who had been employed for at least one year from 1923 up to 1996. The causes of death were obtained from the national cause of death register from 1952 to 2001. Myocardial infarction mortality was obtained by linking personal identification numbers to the national cause of death register. Poisson regression was used for risk estimations on exposure-response relation, and analyses were made on the two age groups 60 years. RESULTS: Relative risks for myocardial infarction mortality in relation to exposure were significantly increased for exposure (0/>0) to WBV (RR: 1.18, 95% CI 1.06-1.31) and dust (RR: 1.15, 95% CI 1.02-1.31), and the results indicated an exposure-response relation for WBV and dust separately. For 60 years and younger, exposure to HAV (0/>0) (RR: 1.34, 95% CI 1.03-1.74) and WBV (0/>0) (RR: 1.39, 95% CI 1.13-1.72) increased the risk of MI mortality. An exposure-response was found for HAV and WBV, as the medium and high exposed categories showed significantly increased risk estimates. None of the exposures significantly increased the risk in the group above 60 years. The increased risk estimates for exposure to WBV remained when adjusting for exposure to dust. CONCLUSIONS: The results for the working-age (

  • 114.
    Björ, Ove
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Edström, Clarence
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Long-term follow-up study of mortality and the incidence of cancer in a cohort of workers at a primary aluminum smelter in Sweden2008In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 34, no 6, p. 463-470Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Previous studies on mortality and the incidence of cancer among workers at primary aluminum smelters have produced conclusive results indicating an elevated risk of bladder cancer. An increased risk of lung cancer has also been reported several times. The objective of this study was to examine mortality and the incidence of cancer at a Swedish aluminum smelter when different neighboring reference populations were used to evaluate any relationships to the length of employment. METHODS: A historical cohort--comprised of 2264 male nonoffice workers employed from 1942 on and tracked up to the year 2000--was examined. With the use of three reference populations for mortality and four for cancer incidence, standardized mortality and incidence ratios were calculated, together with hazard ratios derived from Cox regression models. RESULTS: This study showed an excess risk of mortality due to chronic obstructive lung disease, mental disorders, and diseases of the digestive system among the short-term workers. An elevated risk of cancer was found for the lungs, central nervous system, and esophagus. The highest lung cancer risk was observed for the workers employed for > or = 10 years in the factory when they were compared with the reference group from northern Sweden (standardized incidence ratio 1.99, 95% confidence ratio 1.21-3.07). CONCLUSIONS: The results support previous studies that demonstrated an excess risk of lung cancer, but, in contrast to the results of most studies, cancer of the central nervous system was also elevated. This study did not, however, verify an association between this type of exposure and cancer of the urinary organs.

  • 115.
    Björ, Ove
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Sundsvall Hosp, Dept Occupat & Environm Med, Sundsvall, Sweden.
    A comparison between standard methods and structural nested modelling when bias from a healthy worker survivor effect is suspected: an iron-ore mining cohort study2015In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 72, no 7, p. 536-542Article in journal (Refereed)
    Abstract [en]

    Objectives Iron-ore miners are exposed to extremely dusty and physically arduous work environments. The demanding activities of mining select healthier workers with longer work histories (ie, the Healthy Worker Survivor Effect (HWSE)), and could have a reversing effect on the exposure-response association. The objective of this study was to evaluate an iron-ore mining cohort to determine whether the effect of respirable dust was confounded by the presence of an HWSE. Methods When an HWSE exists, standard modelling methods, such as Cox regression analysis, produce biased results. We compared results from g-estimation of accelerated failure-time modelling adjusted for HWSE with corresponding unadjusted Cox regression modelling results. Results For all-cause mortality when adjusting for the HWSE, cumulative exposure from respirable dust was associated with a 6% decrease of life expectancy if exposed >= 15 years, compared with never being exposed. Respirable dust continued to be associated with mortality after censoring outcomes known to be associated with dust when adjusting for the HWSE. In contrast, results based on Cox regression analysis did not support that an association was present. Conclusions The adjustment for the HWSE made a difference when estimating the risk of mortality from respirable dust. The results of this study, therefore, support the recommendation that standard methods of analysis should be complemented with structural modelling analysis techniques, such as g-estimation of accelerated failure-time modelling, to adjust for the HWSE.

  • 116.
    Björ, Ove
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Burström, Lage
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Is outdoor work associated with elevated rates of cerebrovascular disease mortality?: a cohort study based on iron-ore mining2016In: Journal of Occupational Medicine and Toxicology, ISSN 1745-6673, E-ISSN 1745-6673, Vol. 11, article id 40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A cohort study that examined iron ore mining found negative associations between cumulative working time employed underground and several outcomes, including mortality of cerebrovascular diseases. In this cohort study, and using the same group of miners, we examined whether work in an outdoor environment could explain elevated cerebrovascular disease rates.

    METHODS: This study was based on a Swedish iron ore mining cohort consisting of 13,000 workers. Poisson regression models were used to generate smoothed estimates of standardized mortality ratios and adjusted rate ratios, both models by cumulative exposure time in outdoor work.

    RESULTS: The adjusted rate ratio between employment classified as outdoor work ≥25 years and outdoor work 0-4 years was 1.62 (95 % CI 1.07-2.42). The subgroup underground work ≥15 years deviated most in occurrence of cerebrovascular disease mortality compared with the external reference population: SMR (0.70 (95 % CI 0.56-0.85)).

    CONCLUSIONS: Employment in outdoor environments was associated with elevated rates of cerebrovascular disease mortality. In contrast, work in tempered underground employment was associated with a protecting effect.

  • 117.
    Björ, Ove
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wahlström, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nilsson, Tohr
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Reduced mortality rates in a cohort of long-term underground iron-ore miners2013In: American Journal of Industrial Medicine, ISSN 0271-3586, E-ISSN 1097-0274, Vol. 56, no 5, p. 531-540Article in journal (Refereed)
    Abstract [en]

    Background Historically, working in iron-ore mines has been associated with an increased risk of lung cancer and silicosis. However, studies on other causes of mortality are inconsistent and in the case of cancer incidence, sparse. The aim of this study was to examine the association between iron-ore mining, mortality and cancer incidence.

    Methods A 54-year cohort study on iron-ore miners from mines in northern Sweden was carried out comprising 13,000 workers. Standardized rate ratios were calculated comparing the disease frequency, mortality, and cancer incidence with that of the general population of northern Sweden. Poisson regression was used to evaluate the association between the durations of employment and underground work, and outcome.

    Results Underground mining was associated with a significant decrease in adjusted mortality rate ratios for cerebrovascular and digestive system diseases, and stroke. For several outcomes, elevated standardized rate ratios were observed among blue-collar workers relative to the reference population. However, only the incidence of lung cancer increased with employment time underground (P<0.001).

    Conclusions Long-term iron-ore mining underground was associated with lower rates regarding several health outcomes. This is possibly explained by factors related to actual job activities, environmental exposure, or the selection of healthier workers for long-term underground employment.

    Am. J. Ind. Med. 56:531540, 2013. (c) 2013 Wiley Periodicals, Inc.

  • 118. Björeland, Anders
    et al.
    Blomquist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sätherberg, Anders
    Bergström, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Joint Center - samarbetsprojekt för optimal strålbehandling i närmiljö2004In: Läkartidningen, ISSN 0023-7205, Vol. 101, no 6, p. 472-475Article in journal (Refereed)
  • 119.
    Björkblom, Benny
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Späth, Florentin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    PRE-DIAGNOSTIC PLASMA METABOLITES LINKED TO FUTURE BRAIN TUMOR DEVELOPMENT2018In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, p. 288-289Article in journal (Other academic)
    Abstract [en]

    BACKGROUND: The Northern Sweden Health and Disease Study is a unique population-based biobank linked to the clinical data registries. The samples originate from over 133 000 individuals living in the northern part of Sweden, and primarily collected during health checkups from the age of 40 years. Our project aims to investigate alterations in metabolite signatures in blood plasma of healthy blood donors that later in life developed a tumor. Brain tumors, especially glioblastoma is associated with poor prognosis. To explore early events of metabolic reprograming linked to future diagnosis, we investigated alterations in metabolite concentrations in plasma collected several years before diagnosis with matched healthy controls. MATERIALS AND METHODS: In total 392 analytical samples (256 repeated timepoint and 136 single timepoint, case-control samples) were analyzed using GCTOFMS. Constrained randomization of run order was utilized to maximize information output and minimize the false discovery rate. By use of reference databases, we could with high confidence quantify and identify 150 plasma metabolites. We detected metabolites with significant alterations in concertation between pre-clinical glioma cases and healthy controls by the effect projection approach based on orthogonal partial least squares (OPLSEP). RESULTS AND CONCLUSIONS: For the repeated blood samples, we designed and applied a novel multivariate strategy for high resolution biomarker pattern discovery. We utilize the fact that we have available samples from two repeated time points prior to diagnosis for each future glioma case and their matched controls to construct a small design of experiment (DoE) of four samples for each match pair. The data for each individual DoE was evaluated by OPLS-EP to determine the effect of each individual metabolite in relation to control-case, time and their interaction. Finally, latent significance calculations by means of OPLS were used to extract and evaluate the correct latent biomarker and highlight true significance of individual metabolites. Our study presents an approach to minimize confounding effects due to systematic noise from sampling, the analytical method, as well as take into account personalized metabolic levels over time, enabling biomarker detection within a smaller sample group. We will present and discuss the latest results and biomarkers from this exploratory metabolomics study at the meeting

  • 120.
    Björkblom, Benny
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mörén, Lina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johannesen, Tom Borge
    langseth, Hilde
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Metabolomic screening of pre-diagnostic serum samples identifies association between alpha- and gamma-tocopherols and glioblastoma risk2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 24, p. 37043-37053Article in journal (Refereed)
    Abstract [en]

    Glioblastoma is associated with poor prognosis with a median survival of one year. High doses of ionizing radiation is the only established exogenous risk factor. To explore new potential biological risk factors for glioblastoma, we investigated alterations in metabolite concentrations in pre-diagnosed serum samples from glioblastoma patients diagnosed up to 22 years after sample collection, and undiseased controls. The study points out a latent biomarker for future glioblastoma consisting of nine metabolites (gamma-tocopherol, alpha-tocopherol, erythritol, erythronic acid, myo-inositol, cystine, 2-keto-L-gluconic acid, hypoxanthine and xanthine) involved in antioxidant metabolism. We detected significantly higher serum concentrations of alpha-tocopherol (p=0.0018) and gamma-tocopherol (p=0.0009) in future glioblastoma cases. Compared to their matched controls, the cases showed a significant average fold increase of alpha- and gamma-tocopherol levels: 1.2 for alpha-T (p=0.018) and 1.6 for gamma-T (p=0.003). These tocopherol levels were associated with a glioblastoma odds ratio of 1.7 (alpha-T, 95% CI: 1.0-3.0) and 2.1 (gamma-T, 95% CI: 1.2-3.8). Our exploratory metabolomics study detected elevated serum levels of a panel of molecules with antioxidant properties as well as oxidative stress generated compounds. Additional studies are necessary to confirm the association between the observed serum metabolite pattern and future glioblastoma development.

  • 121.
    Björklund, Emmelie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Blomqvist, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Joel, Hedlin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Persson, Emma
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fowler, Christopher
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Involvement of Fatty Acid Amide Hydrolase and Fatty Acid Binding Protein 5 in the Uptake of Anandamide by Cell Lines with Different Levels of Fatty Acid Amide Hydrolase Expression: A Pharmacological Study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e103479-Article in journal (Refereed)
    Abstract [en]

    Background:

    The endocannabinoid ligand anandamide (AEA) is removed from the extracellular space by a process ofcellular uptake followed by metabolism. In many cells, such as the RBL-2H3 cell line, inhibition of FAAH activity reduces theobserved uptake, indicating that the enzyme regulates uptake by controlling the intra- : extracellular AEA concentrationgradient. However, in other FAAH-expressing cells, no such effect is seen. It is not clear, however, whether these differencesare methodological in nature or due to properties of the cells themselves. In consequence, we have reinvestigated the roleof FAAH in gating the uptake of AEA.Methodology/Principal Findings: The effects of FAAH inhibition upon AEA uptake were investigated in four cell lines: AT1rat prostate cancer, RBL-2H3 rat basophilic leukaemia, rat C6 glioma and mouse P19 embryonic carcinoma cells. SemiquantitativePCR for the cells and for a rat brain lysate confirmed the expression of FAAH. No obvious expression of atranscript with the expected molecular weight of FLAT was seen. FAAH expression differed between cells, but all four couldaccumulate AEA in a manner inhibitable by the selective FAAH inhibitor URB597. However, there was a difference in thesensitivities seen in the reduction of uptake for a given degree of FAAH inhibition produced by a reversible FAAH inhibitor,with C6 cells being more sensitive than RBL-2H3 cells, despite rather similar expression levels and activities of FAAH. Thefour cell lines all expressed FABP5, and AEA uptake was reduced in the presence of the FABP5 inhibitor SB-FI-26, suggestingthat the different sensitivities to FAAH inhibition for C6 and RBL2H3 cells is not due to differences at the level of FABP-5.Conclusions/Significance: When assayed using the same methodology, different FAAH-expressing cells display differentsensitivities of uptake to FAAH inhibition.

  • 122. Bjørge, Tone
    et al.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden..
    Ghaderi, Sara
    Nagel, Gabriele
    Manjer, Jonas
    Tretli, Steinar
    Ulmer, Hanno
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rosendahl, Ann H
    Lang, Alois
    Stattin, Pär
    Stocks, Tanja
    Engeland, Anders
    BMI and weight changes and risk of obesity-related cancers: a pooled European cohort study.2019In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, article id dyz188Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Obesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers.

    METHODS: We pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972-2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models.

    RESULTS: During follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related.

    CONCLUSIONS: Adult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.

  • 123.
    Bjørge, Tone
    et al.
    Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
    Lukanova, Annekatrin
    Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tretli, Steinar
    Cancer Registry of Norway, Institute of Populationbased Cancer Research, Montebello, Oslo, Norway.
    Ulmer, Hanno
    Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
    Manjer, Jonas
    Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Selmer, Randi
    Norwegian Institute of Public Health, Oslo/Bergen, Norway.
    Nagel, Gabriele
    Institute of Empidemiology, Ulm Univesity, Ulm, Germany.
    Almquist, Martin
    Department of Surgery, Lund University Hospital, Lund University, Malmö, Sweden.
    Concin, Hans
    Agency for Preventive and Social Medicine, Bregenz, Austria.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Häggström, Christel
    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.
    Engeland, Anders
    Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
    Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project.2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 7, p. 1737-1745Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Few studies have assessed the metabolic syndrome (MetS) as an entity in relation to breast cancer risk, and results have been inconsistent. We aimed to examine the association between MetS factors (individually and combined) and risk of breast cancer incidence and mortality. METHODS: Two hundred ninety thousand women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, blood pressure, and levels of glucose, cholesterol, and triglycerides. Relative risks (RR) of breast cancer were estimated using Cox proportional hazards regression for each MetS factor in quintiles and for standardized levels (z-scores) and for a composite z-score for the MetS. RESULTS: There were 4,862 incident cases of breast cancer and 633 deaths from breast cancer identified. In women below age 50, there was a decreased risk of incident cancer for the MetS (per 1-unit increment of z-score; RR, 0.83; 95% confidence interval, 0.76-0.90) as well as for the individual factors (except for glucose). The lowest risks were seen among the heaviest women. In women above age 60, there was an increased risk of breast cancer mortality for the MetS (RR, 1.23; 95% confidence interval, 1.04-1.45) and for blood pressure and glucose. The strongest association with mortality was seen for increased glucose concentrations. CONCLUSIONS: The MetS was associated with a decreased risk of incident breast cancer in women below age 50 with high body mass index, and with an increased risk of breast cancer mortality in women above 60. IMPACT: Lifestyle interventions as recommended for cardiovascular disease prevention may be of value to prevent breast cancer mortality in postmenopausal women.

  • 124. Bjørge, Tone
    et al.
    Lukanova, Annekatrin
    Tretli, Steinar
    Manjer, Jonas
    Ulmer, Hanno
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Selmer, Randi
    Nagel, Gabriele
    Almquist, Martin
    Concin, Hans
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. null.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. null.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. null.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. null.
    Engeland, Anders
    null.
    Metabolic risk factors and ovarian cancer in the metabolic syndrome and cancer project2011In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 40, no 6, p. 1667-1677Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No studies have so far evaluated the impact of the metabolic syndrome (MetS) as an entity on ovarian cancer risk. The authors aimed to examine the association between factors in the MetS, individually and combined, and risk of ovarian cancer incidence and mortality. METHODS: Altogether, 290 000 women from Austria, Norway and Sweden were enrolled during 1974-2005, with measurements taken of height, weight, blood pressure and levels of glucose, cholesterol and triglycerides. Relative risks (RRs) of ovarian cancer were estimated using Cox regression for each MetS factor in quintiles and for standardized levels (z-scores), and for a composite z-score for the MetS. RRs were corrected for random error in measurements. RESULTS: During follow-up, 644 epithelial ovarian cancers and 388 deaths from ovarian cancer were identified. There was no overall association between MetS and ovarian cancer risk. Increasing levels of cholesterol [RR 1.52, 95% confidence interval (95% CI) 1.01-2.29, per 1-U increment of z-score] and blood pressure (RR 1.79, 95% CI 1.12-2.86) conferred, however, increased risks of mucinous and endometrioid tumours, respectively. In women below the age of 50 years, there was increased risk of ovarian cancer mortality for MetS (RR 1.52, 95% CI 1.00-2.30). Increasing levels of BMI (RR 1.17, 95% CI 1.01-1.37) conferred increased risk of ovarian cancer mortality in women above the age of 50 years. CONCLUSION: There was no overall association between MetS and ovarian cancer risk. However, increasing levels of cholesterol and blood pressure increased the risks of mucinous and endometrioid tumours, respectively. Increasing levels of BMI conferred an increased risk of ovarian cancer mortality in women above the age of 50 years.

  • 125. Bjørge, Tone
    et al.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lukanova, Annekatrin
    Tretli, Steinar
    Selmer, Randi
    Manjer, Jonas
    Rapp, Kilian
    Ulmer, Hanno
    Almquist, Martin
    Concin, Hans
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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.
    Engeland, Anders
    Metabolic syndrome and endometrial carcinoma2010In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 171, no 8, p. 892-902Article in journal (Refereed)
    Abstract [en]

    The authors examined the association between the metabolic syndrome and risk of incident endometrial and fatal uterine corpus cancer within a large prospective cohort study. Approximately 290,000 women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, systolic and diastolic blood pressure, and circulating levels of glucose, total cholesterol, and triglycerides. Relative risks were estimated using Cox proportional hazards regression. The metabolic syndrome was assessed as a composite z score, as the standardized sum of z scores for body mass index, blood pressure, glucose, cholesterol, and triglycerides. A total of 917 endometrial carcinomas and 129 fatal cancers were identified. Increased risks of incident endometrial carcinoma and fatal uterine corpus cancer were seen for the metabolic syndrome factors combined, as well as for individual factors (except for cholesterol). The relative risk of endometrial carcinoma for the metabolic syndrome was 1.37 (95% confidence interval: 1.28, 1.46) per 1-unit increment of z score. The positive associations between metabolic syndrome factors (both individually and combined) and endometrial carcinoma were confined to the heaviest women. The association between the metabolic syndrome and endometrial carcinoma risk seems to go beyond the risk conferred by obesity alone, particularly in women with a high body mass index.

  • 126. Blein, Sophie
    et al.
    Bardel, Claire
    Danjean, Vincent
    McGuffog, Lesley
    Healey, Sue
    Barrowdale, Daniel
    Lee, Andrew
    Dennis, Joe
    Kuchenbaecker, Karoline B.
    Soucy, Penny
    Terry, Mary Beth
    Chung, Wendy K.
    Goldgar, David E.
    Buys, Saundra S.
    Janavicius, Ramunas
    Tihomirova, Laima
    Tung, Nadine
    Dorfling, Cecilia M.
    van Rensburg, Elizabeth J.
    Neuhausen, Susan L.
    Ding, Yuan Chun
    Gerdes, Anne-Marie
    Ejlertsen, Bent
    Nielsen, Finn C.
    Hansen, Thomas V. O.
    Osorio, Ana
    Benitez, Javier
    Andres Conejero, Raquel
    Segota, Ena
    Weitzel, Jeffrey N.
    Thelander, Margo
    Peterlongo, Paolo
    Radice, Paolo
    Pensotti, Valeria
    Dolcetti, Riccardo
    Bonanni, Bernardo
    Peissel, Bernard
    Zaffaroni, Daniela
    Scuvera, Giulietta
    Manoukian, Siranoush
    Varesco, Liliana
    Capone, Gabriele L.
    Papi, Laura
    Ottini, Laura
    Yannoukakos, Drakoulis
    Konstantopoulou, Irene
    Garber, Judy
    Hamann, Ute
    Donaldson, Alan
    Brady, Angela
    Brewer, Carole
    Foo, Claire
    Evans, D. Gareth
    Frost, Debra
    Eccles, Diana
    Douglas, Fiona
    Cook, Jackie
    Adlard, Julian
    Barwell, Julian
    Walker, Lisa
    Izatt, Louise
    Side, Lucy E.
    Kennedy, M. John
    Tischkowitz, Marc
    Rogers, Mark T.
    Porteous, Mary E.
    Morrison, Patrick J.
    Platte, Radka
    Eeles, Ros
    Davidson, Rosemarie
    Hodgson, Shirley
    Cole, Trevor
    Godwin, Andrew K.
    Isaacs, Claudine
    Claes, Kathleen
    De Leeneer, Kim
    Meindl, Alfons
    Gehrig, Andrea
    Wappenschmidt, Barbara
    Sutter, Christian
    Engel, Christoph
    Niederacher, Dieter
    Steinemann, Doris
    Plendl, Hansjoerg
    Kast, Karin
    Rhiem, Kerstin
    Ditsch, Nina
    Arnold, Norbert
    Varon-Mateeva, Raymonda
    Schmutzler, Rita K.
    Preisler-Adams, Sabine
    Markov, Nadja Bogdanova
    Wang-Gohrke, Shan
    de Pauw, Antoine
    Lefol, Cedrick
    Lasset, Christine
    Leroux, Dominique
    Rouleau, Etienne
    Damiola, Francesca
    Dreyfus, Helene
    Barjhoux, Laure
    Golmard, Lisa
    Uhrhammer, Nancy
    Bonadona, Valerie
    Sornin, Valerie
    Bignon, Yves-Jean
    Carter, Jonathan
    Van Le, Linda
    Piedmonte, Marion
    DiSilvestro, Paul A.
    de la Hoya, Miguel
    Caldes, Trinidad
    Nevanlinna, Heli
    Aittomaki, Kristiina
    Jager, Agnes
    van den Ouweland, Ans M. W.
    Kets, Carolien M.
    Aalfs, Cora M.
    van Leeuwen, Flora E.
    Hogervorst, Frans B. L.
    Meijers-Heijboer, Hanne E. J.
    Oosterwijk, Jan C.
    van Roozendaal, Kees E. P.
    Rookus, Matti A.
    Devilee, Peter
    van der Luijt, Rob B.
    Olah, Edith
    Diez, Orland
    Teule, Alex
    Lazaro, Conxi
    Blanco, Ignacio
    Del Valle, Jesus
    Jakubowska, Anna
    Sukiennicki, Grzegorz
    Gronwald, Jacek
    Lubinski, Jan
    Durda, Katarzyna
    Jaworska-Bieniek, Katarzyna
    Agnarsson, Bjarni A.
    Maugard, Christine
    Amadori, Alberto
    Montagna, Marco
    Teixeira, Manuel R.
    Spurdle, Amanda B.
    Foulkes, William
    Olswold, Curtis
    Lindor, Noralane M.
    Pankratz, Vernon S.
    Szabo, Csilla I.
    Lincoln, Anne
    Jacobs, Lauren
    Corines, Marina
    Robson, Mark
    Vijai, Joseph
    Berger, Andreas
    Fink-Retter, Anneliese
    Singer, Christian F.
    Rappaport, Christine
    Kaulich, Daphne Geschwantler
    Pfeiler, Georg
    Tea, Muy-Kheng
    Greene, Mark H.
    Mai, Phuong L.
    Rennert, Gad
    Imyanitov, Evgeny N.
    Mulligan, Anna Marie
    Glendon, Gord
    Andrulis, Irene L.
    Tchatchou, Sandrine
    Toland, Amanda Ewart
    Pedersen, Inge Sokilde
    Thomassen, Mads
    Kruse, Torben A.
    Jensen, Uffe Birk
    Caligo, Maria A.
    Friedman, Eitan
    Zidan, Jamal
    Laitman, Yael
    Lindblom, Annika
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Arver, Brita
    Loman, Niklas
    Rosenquist, Richard
    Olopade, Olufunmilayo I.
    Nussbaum, Robert L.
    Ramus, Susan J.
    Nathanson, Katherine L.
    Domchek, Susan M.
    Rebbeck, Timothy R.
    Arun, Banu K.
    Mitchell, Gillian
    Karlan, Beth Y.
    Lester, Jenny
    Orsulic, Sandra
    Stoppa-Lyonnet, Dominique
    Thomas, Gilles
    Simard, Jacques
    Couch, Fergus J.
    Offit, Kenneth
    Easton, Douglas F.
    Chenevix-Trench, Georgia
    Antoniou, Antonis C.
    Mazoyer, Sylvie
    Phelan, Catherine M.
    Sinilnikova, Olga M.
    Cox, David G.
    An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers2015In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 17, article id 61Article in journal (Refereed)
    Abstract [en]

    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

  • 127.
    Blomquist, M
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, M G
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, B
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Multileaf collimation of electrons-clinical effects on electron energy modulation and mixed beam therapy depending on treatment head design2002In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 47, no 7, p. 1013-1024Article in journal (Refereed)
    Abstract [en]

    The aim Of this Study was to explore the possibilities of using multileaf-collimated electron beams for advanced radiation therapy with conventional scattering foil flattened beams. Monte Carlo simulations were performed with the aim to improve electron beam characteristics and enable isocentric multileaf collimation. The scattering foil positions, monitor chamber thickness, the MLC location and the amount of He in the treatment head were optimized for three common commercial accelerators. The performance of the three optimized treatment head designs was compared for different SSDs in air. at treatment depth in water and for some clinical cases. The effects of electron/photon beam matching including generalized random and static errors using Gaussian one-dimensional (1D) error distributions, and also electron energy modulation, were studied at treatment depth in beater, The modification of the treatment heads improved the electron beam characteristics and enabled the use of multileaf collimation in isocentric delivery of both electron and photon beams in a mixed beam IMRT procedure.

  • 128.
    Blomquist, M
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ma, C M
    Zackrisson, B
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Comments on 'X-ray energy choice for lung tumour irradiation depends on the density distribution of clonogenic cells'2003In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 48, no 8, p. L29-L30Article in journal (Refereed)
  • 129.
    Blomquist, M
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Li, J S
    Ma, C M
    Zackrisson, B
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Comparison between a conventional treatment energy and 50 MV photons for the treatment of lung tumours2002In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 47, no 6, p. 889-897Article in journal (Refereed)
    Abstract [en]

    Radiation therapy in the thoracic region is difficult due to the presence of many dose-limiting structures and the large density differences that affect the dose distribution. Conventional irradiation techniques use low-energy photon beams to avoid build-up effects superficially in the tumour and increased lateral scattering of the beams. For deep-seated tumours higher beam energies could have lung-sparing properties that would enable dose escalation. A comparison was made for a conventional low photon energy (6 MV) and 50 MV photons for the treatment of a lung tumour. A representative patient geometry was selected, consisting of a small tumour semi-enclosed in lung tissue. Treatment plans were designed using a commercial 3D-pencil beam treatment planning system. The treatment beams designed in the TPS were simulated with the Monte Carlo code EGS4/BEAM and the dose distribution in the phantom created from the patients CT-data was calculated using MCDOSE with identical beam geometry for both energies. The intrinsic difference between the two photon energies implies a sparing effect of lung that can be utilized for dose escalation. For a treatment with two beams the mean total dose to the tumour could be increased by 5.3% for 50 MV, corresponding to 3.2 Gy for a prescription dose of 60 Gy, with the same complication probability for the treated lung as for 6 MV. In conclusion, high-energy beams have qualities that can be taken advantage of for irradiation of lung tumours. Optimum solutions would probably require the use of both high- and low-energy beams.

  • 130.
    Blomquist, M
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Satherberg, A
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zackrisson, B
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Scanned intensity modulations for 50 MV photons1998In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 43, no 5, p. 1185-1197Article in journal (Refereed)
    Abstract [en]

    Optimization of the dose distributions by individual beam compensation is a useful tool in conformal radiation therapy. Intensity modulation by electromagnetic scanning of a narrow elementary beam allows fast dose delivery and causes little change in beam quality compared with other methods, especially for high energies such as 50 MV. Intensity modulated beams from the MM50 accelerator were measured and compared with calculations based on Monte Carlo simulations. Good agreement between measurements and calculations were found, typically within 1% for central dose profiles. The steepest wedge angle that was produced with the scanning beam technique was of 45 degrees or 3.5% cm(-1) for a 20 cm x 20 cm field, slightly varying with depth. The elementary 50 MV photon 'pencil beam' for a full range, high-z bremsstrahlung target, is a wide dose distribution at 10 cm depth in water which limits the modulation gradient and hence the complexity of the modulation by the scanning of a photon pencil beam only. Scanned wedge beam distributions were modelled in the treatment planning system and a pelvic treatment with three fields was used to illustrate a clinical application. The resulting dose volume data were compared for different radiation qualities but with similar beam portals. 'Energy modulation' by field matching with lower photon energies was performed to sharpen the penumbra towards organs at risk.

  • 131.
    Bodén, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Shivappa, Nitin
    Hébert, James R
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    The inflammatory potential of diet in determining cancer risk: a prospective investigation of two dietary pattern scores2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0214551Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Inflammation-related mechanisms may contribute to the link between diet and cancer. We sought to investigate the inflammatory impact of diet on cancer risk using the Dietary inflammatory index (DII) and an adapted Mediterranean diet score (MDS).

    METHODS: This population-based, prospective cohort study used self-reported dietary data from the Västerbotten Intervention Programme, including 100,881 participants, of whom 35,393 had repeated measures. Associations between dietary patterns and cancer risk were evaluated using Cox proportional hazards regression. We also used restricted cubic splines to test for potential non-linear associations.

    RESULTS: A total of 9,250 incident cancer cases were diagnosed during a median follow-up of 15 years. The two dietary patterns were moderately correlated to each other and had similar associations with cancer risk, predominantly lung cancer in men (DII per tertile decrease: Hazard ratio (HR) 0.81 (0.66-0.99), MDS per tertile increase: HR 0.86 (0.72-1.03)), and gastric cancer in men (DII: 0.73 (0.53-0.99), MDS: 0.73 (0.56-0.96)). Associations were, in general, found to be linear. We found no longitudinal association between 10-year change in diet and cancer risk.

    CONCLUSION: We confirm small, but consistent and statistically significant associations between a more anti-inflammatory or healthier diet and reduced risk of cancer, including a lower risk of lung and gastric cancer in men. The dietary indexes produced similar associations with respect to the risk of cancer.

  • 132.
    Bodén, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shivappa, Nitin
    Hebert, James R
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dietary inflammatory index and risk of first myocardial infarction: a prospective population-based study2017In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 16, article id 21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DII(TM)), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up.

    METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population.

    RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available.

    CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.

  • 133.
    Boman, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Endometrial carcinoma: steroid hormones and receptors in relation to proliferation1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The significance of the hormonal milieu for endometrial changes is as well-known as its link with endometrial carcinoma. Unopposed oestradiol treatment is shown to increase the incidence for this cancer. Obesity leads to elevated levels of oestrogens and is a risk factor for endometrial carcinoma. An association between high tumour proliferation and prognosis is a general feature of human cancer. Tumour growth can be expressed as proliferation rate and flow cytometry (FCM) is a sensitive and reproducable method to estimate S-phase fraction (SPF) and ploidy level. Both parameters have been shown to correlate with prognosis. Sex steroid hormone levels were analysed together with clinical parameters, SPF, and receptors in established endometrial carcinoma.

    The study consisted of postmenopausal women with endometrial adeno­carcinoma. H ormones were analysed in 127 patients, 99 were analysed for FCM and 60 for oestrogen and progesterone receptors. RIA technique was used for hormone assay of oestrone, oestradiol, progesterone, androstenedione and testosterone plasma levels. The receptors were analysed with an immunohistochemical method, and SPF and ploidy level by flow cytometry.

    A wide range of oestrogen concentrations was found. Some patients had levels comparable to fertile women. Strong correlations were found between body mass index, weight and depth of uterine cavity. No relations were found between receptors and SPF, apart from oestrogen- receptor positive tumours having a lower SPF when compared with receptor negative tumours. The influence of oestradiol on tumour proliferation expressed as SPF was ambiguous. SPF was increased with higher oestradiol levels in the group of peri-diploid, well-differentiated tumours, while a negative correlation was found for the peri-diploid, moderately differentiated tumours. The aneuploid and poorly differenti­ated tumours had a high SPF regardless of oestradiol concentration. The association between progesterone concentration and SPF was of a more general nature. Progesterone above a threshold level was related to a lower SPF in well-differentiated and moderately differentiated tumours. Thus endogenous progesterone seems to play a role in controlling the tumour’s proliferation activity, in contrast to oestradiol, that had a role which did not appear to relate to proliferation activity in any specific direction. The only stimulative association was seen in well-differentiated tumours, but SPF was still below the mean value for all diploid tumours.

  • 134. Bondy, Melissa
    et al.
    Bainbridge, Matthew
    Jhangiani, Shalini
    Jalali, Ali
    Plon, Sharon E.
    Armstrong, Georgina
    Bernstein, Jonine
    Claus, Elizabeth
    Davis, Faith
    Houlston, Richard
    Il'yasova, Dora
    Jenkins, Robert
    Johansen, Christoffer
    Lachance, Daniel
    Lai, Rose
    Lau, Ching
    Merrell, Ryan
    Olson, Sara
    Sadetzki, Siegal
    Schildkraut, Joellen
    Shete, Sanjay
    Barnholtz-Sloan, Jill
    Wrensch, Margaret
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gibbs, Richard A.
    POT1 GERMLINE MUTATIONS MAY EXPLAIN A SUBSET OF FAMILIAL GLIOMA: A REPORT FROM THE GLIOGENE CONSORTIUM2013In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 15, no Supplement: 3, p. 89-89Article in journal (Other academic)
  • 135. Bondy, Melissa L
    et al.
    Scheurer, Michael E
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Barnholtz-Sloan, Jill S
    Davis, Faith G
    Il'yasova, Dora
    Kruchko, Carol
    McCarthy, Bridget J
    Rajaraman, Preetha
    Schwartzbaum, Judith A
    Sadetzki, Siegal
    Schlehofer, Brigitte
    Tihan, Tarik
    Wiemels, Joseph L
    Wrensch, Margaret
    Buffler, Patricia A
    Brain tumor epidemiology: consensus from the Brain Tumor Epidemiology Consortium.2008In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 113, no 7 Suppl, p. 1953-1968Article in journal (Refereed)
    Abstract [en]

    Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the group's consensus on the current state of scientific findings, and they present a consensus on research priorities to identify which important areas the science should move to address.

  • 136.
    Bordás, Pál
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Evaluation of the effectiveness of mammography screening in Northern Sweden.2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Service screening with mammography was implemented in Northern Sweden between 1989 and 1998, covering 190,000 women aged 40-74 years constituting the target population in the area.

    The aim of this thesis was the evaluation of mammography screening in Northern Sweden with special focus on selected screening performance indicators and on the disease outcome.

    We analysed interval cancer (IC) incidence and episode sensitivity in the Norrbotten Mammography Screening Programme (NMSP) for the period 1989-2002. An overall IC rate at 1.1/1000 and IC rate ratio at 38% was found and epsiode sensitivity was estimated at 62-73%, in concert with reference values of the European guidelines.

    Radiological classification of the IC cases in three rounds of the NMSP showed that true, occult, missed and minimal signs IC, were present in 48%, 10%, 14% and 28% of the cases.

    We analysed early death from breast cancer (n=342) in Northern Sweden during the first five years of mammography service screening. Most fatal cases were advanced and incurable on diagnosis. In a few screen-detected cases with favourable prognostic factors the fatal outcome was unexpected.

    We estimated breast cancer survival by detection mode in 5120 women with breast cancer. We found a significantly favourable survival among IC cases compared to cases among uninvited.

    We studied breast cancer mortality in relation to mammography screening. Our findings indicated a long-term reduction of breast cancer mortality by 26-30% among women invited to screening and by 31-35% among women screened compared to not screened.

    We conclude from our evaluation of the mammography screening in Northern Sweden that women benefited from this public health intervention in form of improved survival and reduced mortality.

  • 137.
    Bordás, Pál
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    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.
    Cajander, Stefan
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Early breast cancer deaths in women aged 40-74 years diagnosed during the first 5 years of organised mammography service screening in north Sweden2004In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 13, no 4, p. 276-283Article in journal (Refereed)
  • 138.
    Bordás, Pál
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    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.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Interval cancer incidence and episode sensitivity in the Norrbotten mammography screening programme, Sweden2009In: Journal of Medical Screening, ISSN 0969-1413, E-ISSN 1475-5793, Vol. 16, no 1, p. 39-45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the interval cancer incidence, its determinants and the episode sensitivity in the Norrbotten Mammography Screening Programme (NMSP).

    SETTING: Since 1989, women aged 40-74 years (n = 55,000) have been invited to biennial screening by the NMSP, Norrbotten county, Sweden.

    METHODS: Data on 1047 invasive breast cancers from six screening rounds of the NMSP (1989-2002) were collected. We estimated the invasive interval cancer rates, rate ratios and the episode sensitivity using the detection and incidence methods. A linear Poisson-model was used to analyse association between interval cancer incidence and sensitivity.

    RESULTS: 768 screen-detected and 279 interval cancer cases were identified. The rate ratio of interval cancer decreased with age. The 50-59 year age group showed the highest rate ratio (RR = 0.52, 95% CI 0.41-0.65) and the 70-74 year age group the lowest (RR = 0.23, 95% CI 0.15-0.36). The rate ratios for the early (0-12 months) and late (13-24 months) interval cancers were similar (RR = 0.18, 95% CI 0.15-0.22 and 0.20, 95% CI 0.17-0.24). There was a significantly lower interval cancer incidence in the prevalence round as compared with the incidence rounds. According to the detection method the episode sensitivity increased with age from 57% in the age group 40-49 years to 84% in the age group 70-74 years. The corresponding figures for the incidence method were 50% and 77%, respectively.

    CONCLUSION: Our study showed an interval cancer incidence of 38% and the episode sensitivity of 62-73%, depending on the method of calculation. Our results are of clinically acceptable level and concert with the reference values of the European guidelines.

  • 139.
    Bordás, Pál
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    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.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Survival from invasive breast cancer among interval cases in the mammography screening programmes of northern Sweden2007In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 16, no 1, p. 47-54Article in journal (Refereed)
  • 140.
    Bordás, Pál
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Håkan
    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 Global Health.
    Péntek, Zoltán
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Radiological review of interval cancer in the Norrbotten mammography screening program, SwedenManuscript (preprint) (Other academic)
  • 141. Borena, Wegene
    et al.
    Edlinger, Michael
    Bjørge, Tone
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lindkvist, Björn
    Nagel, Gabriele
    Engeland, Anders
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
    Strohmaier, Susanne
    Manjer, Jonas
    Selmer, Randi
    Tretli, Steinar
    Concin, Hans
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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.
    Ulmer, Hanno
    A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, p. e89368-Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC). Methods: The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements. Results: During an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73). Conclusion: This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.

  • 142. Borena, Wegene
    et al.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Strohmaier, Susanne
    Nagel, Gabriele
    Bjørge, Tone
    Manjer, Jonas
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Selmer, Randi
    Almquist, Martin
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Engeland, Anders
    Tretli, Steinar
    Concin, Hans
    Strasak, Alexander
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ulmer, Hanno
    Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study2011In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 2, p. 291-299Article in journal (Refereed)
    Abstract [en]

    Data from our study provided evidence for a possible role of serum triglycerides in cancer development.

  • 143. Borena, Wegene
    et al.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Strohmaier, Susanne
    Strasak, Alexander
    Manjer, Jonas
    Johansen, Dorthe
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rapp, Kilian
    Concin, Hans
    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
    Long-term temporal trends in cardiovascular and metabolic risk factors2009In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 121, no 19-20, p. 623-630Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Metabolic factors such as obesity, hypertension, dyslipidemia and hyperglycemia have consistently been associated with increased risk of cardiovascular disease. There is also growing evidence that these factors are linked to cancer incidence and mortality. The aim of this study was to investigate long-term trends in major metabolic risk factors in three large cohorts. MATERIALS AND METHODS: Data from 239,602 individuals aged 25-64 years participating in health examinations between 1976 and 2005 were used to estimate prevalence and trends in five risk factors. RESULTS: Irrespective of geographic location, individual metabolic risk factors showed divergent trends across the observation period. Whereas obesity and hyperglycemia in men increased by a per decade ratio of 1.54 (95% CI: 1.42-1.66) and 1.62 (95% CI: 1.49-1.76), respectively, and in women by 1.48 (95% CI: 1.41-1.56) and 1.66 (95% CI: 1.57-1.75), hypertension decreased by 0.71 (95% CI: 0.68-0.74) in men and 0.83 (95% CI: 0.79-0.86) in women. Dyslipidemia increased from the 1970s to the 1980s but declined in the succeeding decade. A combination of three or more of these risk factors increased significantly in men by a ratio of 1.15 (95% CI: 1.08-1.22) per decade and in women by 1.20 (95% CI: 1.15-1.27). CONCLUSION: The study shows that individual metabolic risk factors followed divergent trends over the period of three decades even though the combination of three or more risk factors used as a proxy for the metabolic syndrome appeared to be stable over the last two of the decades. The two key components of the syndrome, namely BMI and glucose levels, increased significantly and deserve professional attention.

  • 144. Borena, Wegene
    et al.
    Strohmaier, Susanne
    Lukanova, Annekatrin
    Bjørge, Tone
    Lindkvist, Björn
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Edlinger, Michael
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Nagel, Gabriele
    Manjer, Jonas
    Engeland, Anders
    Selmer, Randi
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tretli, Steinar
    Concin, Hans
    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.
    Ulmer, Hanno
    Metabolic risk factors and primary liver cancer in a prospective study of 578,700 adults2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 1, p. 193-200Article in journal (Refereed)
    Abstract [en]

    Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not been investigated. The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z-score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z-score. RRs were corrected for random error in measurements. During an average follow-up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z-score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub-cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24-1.58), mid blood pressure 2.08 (0.95-4.73), blood glucose 2.13 (1.55-2.94) cholesterol 0.62 (0.51-0.76) and serum triglycerides 0.85 (0.65-1.10). The RR per one unit increment of the MetS z-score was 1.35 (1.12-1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.

  • 145. Borgå, Olof
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bjermo, Helena
    Lilienberg, Elsa
    Heldring, Nina
    Loman, Niklas
    Maximum Tolerated Dose and Pharmacokinetics of Paclitaxel Micellar in Patients with Recurrent Malignant Solid Tumours: A Dose-Escalation Study2019In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 36, no 5, p. 1150-1163Article in journal (Refereed)
    Abstract [en]

    Introduction: A water-soluble Cremophor EL-free formulation of paclitaxel, in which retinoic acid derivates solubilize paclitaxel by forming micelles (paclitaxel micellar), was studied for the first time in man to establish the maximum tolerated dose (MTD) and to characterize the pharmacokinetics (PK).

    Methods: This was an open-label, one-arm, dose-escalating study in patients with advanced solid malignant tumours, for which no standard therapy was available or had failed. Paclitaxel micellar was given as 1-h intravenous infusion every 21 days for 3 cycles, mainly without premedication. Plasma samples were collected during 24 h at the first cycle and paclitaxel concentrations were assayed by high-performance liquid chromatography. PK was evaluated using a two-compartment model.

    Results: Thirty-four patients received paclitaxel micellar at doses ranging between 90 and 275 mg/m2. MTD was established as 250 mg/m2. Fatigue and neuropathy were the most frequent dose-limiting toxicities. No hypersensitivity reactions were observed. PK of paclitaxel was evaluated in 25 data sets. Paclitaxel micellar had a rapid initial distribution phase, mean half-life 0.55 h, estimated to be completed 3 h after dosing and a mean terminal half-life of 8.8 h. Mean clearance was 13.4 L/h/m2 with fivefold interindividual variability. The residual areas after 10 h and 24 h were 15.7 ± 8.6% and 5.7 ± 3.9% of the area under the plasma concentration–time curve to infinite time (AUCinf), respectively.

    Conclusion: No new side effects unknown for paclitaxel were observed. Maximum plasma concentration (Cmax) and AUCinf showed a tendency to increase linearly with dose within the 150–275 mg/m2dose range. The possibility to administer paclitaxel micellar without steroid premedication makes it an attractive candidate for further studies in combination with immunotherapy.

    Trial Registration: EudraCT no: 2004-001821-54.

  • 146. Bosco, Cecilia
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Holmberg, Lars
    Nilsson, Per
    Gunnlaugsson, Adalsteinn
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Hemelrijck, Mieke
    Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events2017In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 97, no 5, p. 1026-1031Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa). Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age-and county-matched comparison cohort of PCa-free men (n = 46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression. Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis. Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.

  • 147. Bottomley, A.
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Taphoorn, M. J. B.
    Cloughesy, T.
    Wick, W.
    Mason, W.
    Saran, F.
    Nishikawa, R.
    Ravelo, A.
    Chinot, O. L.
    Health-related quality of life (HRQoL) in AVAglio, a randomized, placebo (P)-controlled phase III study of bevacizumab (B), temozolomide (T) and radiotherapy (RI) in patients (pts) with newly diagnosed glioblastoma (GBM)2013In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no Supplement 2, p. S780-S780, Meeting Abstract: 3316Article in journal (Other academic)
  • 148.
    Bovinder Ylitalo, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nordstrand, Annika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    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.
    Lerner, Ulf H.
    Umeå University, Faculty of Medicine, Department of Odontology. Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bone remodeling in relation to androgen receptor activity in prostate cancer bone metastases2018In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 16, p. 50-50Article in journal (Other academic)
  • 149.
    Bovinder Ylitalo, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Egevad, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, no 5, p. 776-787Article in journal (Refereed)
    Abstract [en]

    Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy.

    Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-naïve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription–polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.

    Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non–AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non–AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.

    Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.

  • 150.
    Bovinder Ylitalo, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    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.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Integrated DNA methylation and gene expression analysis of molecular heterogeneity in prostate cancer bone metastasisManuscript (preprint) (Other academic)
1234567 101 - 150 of 1278
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