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  • 1.
    Aasa, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Bengtsson, Victor
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Physiotherapy.
    Berglund, Lars
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Variability of lumbar spinal alignment among power- and weightlifters during the deadlift and barbell back squat2022In: Sports Biomechanics, ISSN 1476-3141, E-ISSN 1752-6116, Vol. 21, no 6, p. 707-717Article in journal (Refereed)
    Abstract [en]

    The aims of the study were to evaluate the relative and absolute variability of upper (T11-L2) and lower (L2-S2) lumbar spinal alignment in power- and weightlifters during the deadlift and back squat exercises, and to compare this alignment between the two lifting groups. Twenty-four competitive powerlifters (n = 14) and weightlifters (n = 10) performed three repetitions of the deadlift and the back squat exercises using a load equivalent to 70% of their respective one-repetition maximum. The main outcome measures were the three-dimensional lumbar spinal alignment for start position, minimum and maximum angle of their spinal alignment, and range of motion measured using inertial measurement units. Relative intra-trial reliability was calculated using the two-way random model intraclass correlation coefficient (ICC) and absolute reliability with minimal detectable change (MDC). The ICC ranged between 0.69 and 0.99 and the MDC between 1 degrees-8 degrees for the deadlift. Corresponding figures for the squat were 0.78-0.99 and 1 degrees-6 degrees. In all participants during both exercises, spinal adjustments were made in both thoracolumbar and lumbopelvic areas in all three dimensions. In conclusion, when performing three repetitions of the deadlift and the squat, lumbar spinal alignment of the lifters did not change much between repetitions and did not differ significantly between power- and weightlifters.

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  • 2. Abbas, Sascha
    et al.
    Linseisen, Jakob
    Rohrmann, Sabine
    Chang-Claude, Jenny
    Peeters, Petra H
    Engel, Pierre
    Brustad, Magritt
    Lund, Eiliv
    Skeie, Guri
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Kaaks, Rudolf
    Boeing, Heiner
    Buijsse, Brian
    Adarakis, George
    Ouranos, Vassilis
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Buckland, Genevieve
    Suárez, Marcial Vicente Argüelles
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Amiano, Pilar
    Manjer, Jonas
    Wirfält, Elisabet
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bueno-de-Mesquita, H B
    van Duijnhoven, Fränzel J B
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Fedirko, Veronika
    Romieu, Isabelle
    Gallo, Valentina
    Norat, Teresa
    Wark, Petra A
    Riboli, Elio
    Dietary intake of vitamin D and calcium and breast cancer risk in the European prospective investigation into cancer and nutrition2013In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 65, no 2, p. 178-187Article in journal (Refereed)
    Abstract [en]

    Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.

  • 3.
    AbdelMageed, Manar
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
    Ali, Haytham
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
    Ohlsson, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Lindmark, Gudrun
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome2019In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 20, no 22, article id 5793Article in journal (Refereed)
    Abstract [en]

    hemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

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  • 4.
    AbdelMageed, Manar
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Ismail, Hager
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Ohlsson, Lina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Lindmark, Gudrun
    Institution of Clinical Sciences, Lund University, Helsingborg, Sweden.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Clinical significance of stem cell biomarkers epcam, lgr5 and lgr4 mrna levels in lymph nodes of colon cancer patients2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 1, article id 403Article in journal (Refereed)
    Abstract [en]

    The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan‐Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA cop-ies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12‐year follow‐up (p = 0.022, p = 0.005 and p = 0.011, respec-tively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.

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  • 5.
    Abdel-Shafi, Seham
    et al.
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Nemr, Mona
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    Enan, Gamal
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    Osman, Ali
    Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sitohy, Mahmoud
    Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
    Isolation and characterization of antibacterial conglutinins from Lupine seeds2023In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 28, no 1, article id 35Article in journal (Refereed)
    Abstract [en]

    The main target of this work is to discover new protein fractions from natural resources with high antibacterial action. The 7S and 11S globulin fractions, as well as the basic subunit (BS), were isolated from lupine seeds (Lupinus termis), chemically characterized, and screened for antibacterial activity against seven pathogenic bacteria. SDS-PAGE revealed molecular weights ranging from 55 to 75 kDa for 7S globulin, 20–37 kD for 11S globulin, and 20 kD for the BS. 11S globulin and the BS migrated faster on Urea-PAGE toward the cathode compared to 7S globulin. FTIR and NMR showed different spectral patterns between the 7S and 11S globulins but similar ones between 11S globulin and the BS. The MICs of the BS were in the range of 0.05–2 μg/mL against Listeria monocytogenes, Klebsiella oxytoca, Proteus mirabilis, Staphylococcus aureus, Listeria ivanovii, Salmonella typhimurium, and Pseudomonas aeruginosa compared to higher values for 11S globulin. The BS surpassed 11S globulin in antibacterial action, while 7S globulin showed no effect. The MICs of 11S globulin and the BS represented only 5% and 2.5% of the specific antibiotic against L. monocytogenes, respectively. Scanning electron microscopy (SEM) demonstrated different signs of cellular deformation and decay in the protein-treated bacteria, probably due to interaction with the bacterial cell wall and membranes. 11S globulin and the BS can be nominated as effective food biopreservatives.

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  • 6.
    Abdel-Shafi, Seham
    et al.
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Serwy, Heba
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Zawahry, Yehia
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    Zaki, Maysaa
    Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sitohy, Mahmoud
    Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
    The Association between icaA and icaB Genes, Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Staphylococci spp.2022In: Antibiotics, ISSN 0066-4774, E-ISSN 2079-6382, Vol. 11, no 3, article id 389Article in journal (Refereed)
    Abstract [en]

    Sixty-six (66) Staphylococcus bacterial isolates were withdrawn from separate clinical samples of hospitalized patients with various clinical infections. Conventional bacteriological tests identified the species of all isolates, and standard microbiological techniques differentiated them into CoPS or CoNS. Their biofilm development was followed by an analysis via the MTP (microtiter tissue culture plates) technique, and we then investigated the presence/absence of icaA and icaB, which were qualified in the top-30 potent biofilm-forming isolates. Thirteen isolates (46.7%) showed the presence of one gene, six (20%) isolates exhibited the two genes, while ten (33.3%) had neither of them. The formation of staphylococci biofilms in the absence of ica genes may be related to the presence of other biofilm formation ica-independent mechanisms. CoPS was the most abundant species among the total population. S. aureus was the sole representative of CoPS, while S. epidermidis was the most abundant form of CoNS. Antibiotic resistance was developing against the most frequently used antimicrobial drugs, while vancomycin was the least-resisted drug. The totality of the strong and medium-strength film-forming isolates represented the majority proportion (80%) of the total investigated clinical samples. The biochemical pattern CoPS is associated with antibiotic resistance and biofilm formation and can be an alarming indicator of potential antibiotic resistance.

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  • 7. Abdukalikova, Anara
    et al.
    Kleyko, Denis
    Osipov, Evgeny
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Detection of Atrial Fibrillation From Short ECGs: Minimalistic Complexity Analysis for Feature-Based Classifiers2018In: 2018 Computing in Cardiology Conference (CinC), IEEE, 2018Conference paper (Refereed)
    Abstract [en]

    In order to facilitate data-driven solutions for early detection of atrial fibrillation (AF), the 2017 CinC conference challenge was devoted to automatic AF classification based on short ECG recordings. The proposed solutions concentrated on maximizing the classifiers F-1 score, whereas the complexity of the classifiers was not considered. However, we argue that this must be addressed as complexity places restrictions on the applicability of inexpensive devices for AF monitoring outside hospitals. Therefore, this study investigates the feasibility of complexity reduction by analyzing one of the solutions presented for the challenge.

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  • 8. Abdulla, Maysaa
    et al.
    Hollander, Peter
    Pandzic, Tatjana
    Mansouri, Larry
    Ednersson, Susanne Bram
    Andersson, Per-Ola
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Fors, Maja
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Petersen, Helga Munch
    Asmar, Fazila
    Gronbaek, Kirsten
    Enblad, Gunilla
    Cavelier, Lucia
    Rosenquist, Richard
    Amini, Rose-Marie
    Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma2020In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 95, no 1, p. 57-67Article in journal (Refereed)
    Abstract [en]

    The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.

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  • 9.
    Abdullah Nasir, Ahmad
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herdenberg, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ligand-specific regulation of transforming growth factor beta superfamily factors by leucine-rich repeats and immunoglobulin-like domains proteins2023In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 8, article id e0289726Article in journal (Refereed)
    Abstract [en]

    Leucine-rich repeats and immunoglobulin-like domains (LRIG) are transmembrane proteins shown to promote bone morphogenetic protein (BMP) signaling in Caenorhabditis elegans, Drosophila melanogaster, and mammals. BMPs comprise a subfamily of the transforming growth factor beta (TGFβ) superfamily, or TGFβ family, of ligands. In mammals, LRIG1 and LRIG3 promote BMP4 signaling. BMP6 signaling, but not BMP9 signaling, is also regulated by LRIG proteins, although the specific contributions of LRIG1, LRIG2, and LRIG3 have not been investigated, nor is it known whether other mammalian TGFβ family members are regulated by LRIG proteins. To address these questions, we took advantage of Lrig-null mouse embryonic fibroblasts (MEFs) with doxycycline-inducible LRIG1, LRIG2, and LRIG3 alleles, which were stimulated with ligands representing all the major TGFβ family subgroups. By analyzing the signal mediators pSmad1/5 and pSmad3, as well as the induction of Id1 expression, we showed that LRIG1 promoted BMP2, BMP4, and BMP6 signaling and suppressed GDF7 signaling; LRIG2 promoted BMP2 and BMP4 signaling; and LRIG3 promoted BMP2, BMP4, BMP6, and GDF7 signaling. BMP9 and BMP10 signaling was not regulated by individual LRIG proteins, however, it was enhanced in Lrig-null cells. LRIG proteins did not regulate TGFβ1-induced pSmad1/5 signaling, or GDF11- or TGFβ1-induced pSmad3 signaling. Taken together, our results show that some, but not all, TGFβ family ligands are regulated by LRIG proteins and that the three LRIG proteins display differential regulatory effects. LRIG proteins thereby provide regulatory means for the cell to further diversify the signaling outcomes generated by a limited number of TGFβ family ligands and receptors.

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  • 10.
    Abdullah Nasir, Ahmad
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Herdenberg, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Oncology Research Laboratory, NUS M31, Umeå, Sweden.
    Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 8585Article in journal (Refereed)
    Abstract [en]

    Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.

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  • 11. Abelsson, J
    et al.
    Merup, M
    Birgegård, G
    WeisBjerrum, O
    Brinch, L
    Brune, M
    Johansson, P
    Kauppila, M
    Lenhoff, S
    Liljeholm, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malm, C
    Remes, K
    Vindelöv, L
    Andréasson, B
    The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries.2012In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 47, no 3, p. 380-386Article in journal (Refereed)
    Abstract [en]

    Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.

  • 12. Abrahamsson, Niclas
    et al.
    Borjesson, Joey Lau
    Sundbom, Magnus
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, F. Anders
    Eriksson, Jan W.
    Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 13.
    Adjeiwaah, Mary
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Quality assurance for magnetic resonance imaging (MRI) in radiotherapy2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Magnetic resonance imaging (MRI) utilizes the magnetic properties of tissues to generate image-forming signals. MRI has exquisite soft-tissue contrast and since tumors are mainly soft-tissues, it offers improved delineation of the target volume and nearby organs at risk. The proposed Magnetic Resonance-only Radiotherapy (MR-only RT) work flow allows for the use of MRI as the sole imaging modality in the radiotherapy (RT) treatment planning of cancer. There are, however, issues with geometric distortions inherent with MR image acquisition processes. These distortions result from imperfections in the main magnetic field, nonlinear gradients, as well as field disturbances introduced by the imaged object. In this thesis, we quantified the effect of system related and patient-induced susceptibility geometric distortions on dose distributions for prostate as well as head and neck cancers. Methods to mitigate these distortions were also studied.

    In Study I, mean worst system related residual distortions of 3.19, 2.52 and 2.08 mm at bandwidths (BW) of 122, 244 and 488 Hz/pixel up to a radial distance of 25 cm from a 3T PET/MR scanner was measured with a large field of view (FoV) phantom. Subsequently, we estimated maximum shifts of 5.8, 2.9 and 1.5 mm due to patient-induced susceptibility distortions. VMAT-optimized treatment plans initially performed on distorted CT (dCT) images and recalculated on real CT datasets resulted in a dose difference of less than 0.5%.

     The magnetic susceptibility differences at tissue-metallic,-air and -bone interfaces result in local B0 magnetic field inhomogeneities. The distortion shifts caused by these field inhomogeneities can be reduced by shimming.  Study II aimed to investigate the use of shimming to improve the homogeneity of local  B0 magnetic field which will be beneficial for radiotherapy applications. A shimming simulation based on spherical harmonics modeling was developed. The spinal cord, an organ at risk is surrounded by bone and in close proximity to the lungs may have high susceptibility differences. In this region, mean pixel shifts caused by local B0 field inhomogeneities were reduced from 3.47±1.22 mm to 1.35±0.44 mm and 0.99±0.30 mm using first and second order shimming respectively. This was for a bandwidth of 122 Hz/pixel and an in-plane voxel size of 1×1 mm2.  Also examined in Study II as in Study I was the dosimetric effect of geometric distortions on 21 Head and Neck cancer treatment plans. The dose difference in D50 at the PTV between distorted CT and real CT plans was less than 1.0%.

    In conclusion, the effect of MR geometric distortions on dose plans was small. Generally, we found patient-induced susceptibility distortions were larger compared with residual system distortions at all delineated structures except the external contour. This information will be relevant when setting margins for treatment volumes and organs at risk.  

    The current practice of characterizing MR geometric distortions utilizing spatial accuracy phantoms alone may not be enough for an MR-only radiotherapy workflow. Therefore, measures to mitigate patient-induced susceptibility effects in clinical practice such as patient-specific correction algorithms are needed to complement existing distortion reduction methods such as high acquisition bandwidth and shimming.

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  • 14.
    Adjeiwaah, Mary
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Quality assurance for magnetic resonance imaging (MRI) in radiotherapy2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The use of Magnetic Resonance Imaging (MRI) in the radiotherapy (RT) treatment planning workflow is increasing. MRI offers superior soft-tissue contrast compared to Computed Tomography (CT) and therefore improves the accuracy in target volume definitions. There are, however concerns with inherent geometric distortions from system- (gradient nonlinearities and main magnetic field inhomogeneities) and patient-related sources (magnetic susceptibility effect and chemical shift). The lack of clearly defined quality assurance (QA) procedures has also raised questions on the ability of current QA protocols to detect common image quality degradations under radiotherapy settings. To fully implement and take advantage of the benefits of MRI in radiotherapy, these concerns need to be addressed.

    In Papers I and II, the dosimetric impact of MR distortions was investigated. Patient CTs (CT) were deformed with MR distortion vector fields (from the residual system distortions after correcting for gradient nonlinearities and patient-induced susceptibility distortions) to create distorted CT (dCT) images. Field parameters from volumetric modulated arc therapy (VMAT) treatment plans initially optimized on dCT data sets were transferred to CT data to compute new treatment plans. Data from 19 prostate and 21 head and neck patients were used for the treatment planning. The dCT and CT treatment plans were compared to determine the impact of distortions on dose distributions. No clinically relevant dose differences between distorted CT and original CT treatment plans were found. Mean dose differences were < 1.0% and < 0.5% at the planning target volume (PTV) for the head and neck, and prostate treatment plans, respectively. 

    Strategies to reduce geometric distortions were also evaluated in Papers I and II. Using the vendor-supplied gradient non-linearity correction algorithm reduced overall distortions to less than half of the original value. A high acquisition bandwidth of 488 Hz/pixel (Paper I) and 488 Hz/mm (Paper II) kept the mean geometric distortions at the delineated structures below 1 mm. Furthermore, a patient-specific active shimming method implemented in Paper II significantly reduced the number of voxels with distortion shifts > 2 mm from 15.4% to 2.0%.

    B0 maps from patient-induced magnetic field inhomogeneities obtained through direct measurements and by simulations that used MR-generated synthetic CT (sCT) data were compared in Paper III. The validation showed excellent agreement between the simulated and measured B0 maps.

    In Paper IV, the ability of current QA methods to detect common MR image quality degradations under radiotherapy settings were investigated. By evaluating key image quality parameters, the QA protocols were found to be sensitive to some of the introduced degradations. However, image quality issues such as those caused by RF coil failures could not be adequately detected.

    In conclusion, this work has shown the feasibility of using MRI data for radiotherapy treatment planning as distortions resulted in a dose difference of less than 1% between distorted and undistorted images. The simulation software can be used to produce accurate B0 maps, which could then be used as the basis for the effective correction of patient-induced field inhomogeneity distortions and for the QA verification of sCT data. Furthermore, the analysis of the strengths and weaknesses in current QA tools for MRI in RT contribute to finding better methods to efficiently identify image quality errors.

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  • 15.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Joakim H.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Dosimetric Impact of MRI Distortions: A Study on Head and Neck Cancers2019In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 103, no 4, p. 994-1003Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the effect of magnetic resonance (MR) imaging (MRI) geometric distortions on head and neck radiation therapy treatment planning (RTP) for an MRI-only RTP. We also assessed the potential benefits of patient-specific shimming to reduce the magnitude of MR distortions for a 3-T scanner.

    Methods and Materials: Using an in-house Matlab algorithm, shimming within entire imaging volumes and user-defined regions of interest were simulated. We deformed 21 patient computed tomography (CT) images with MR distortion fields (gradient nonlinearity and patient-induced susceptibility effects) to create distorted CT (dCT) images using bandwidths of 122 and 488 Hz/mm at 3 T. Field parameters from volumetric modulated arc therapy plans initially optimized on dCT data sets were transferred to CT data to compute a new plan. Both plans were compared to determine the impact of distortions on dose distributions.

    Results: Shimming across entire patient volumes decreased the percentage of voxels with distortions of more than 2 mm from 15.4% to 2.0%. Using the user-defined region of interest (ROI) shimming strategy, (here the Planning target volume (PTV) was the chosen ROI volume) led to increased geometric for volumes outside the PTV, as such voxels within the spinal cord with geometric shifts above 2 mm increased from 11.5% to 32.3%. The worst phantom-measured residual system distortions after 3-dimensional gradient nonlinearity correction within a radial distance of 200 mm from the isocenter was 2.17 mm. For all patients, voxels with distortion shifts of more than 2 mm resulting from patient-induced susceptibility effects were 15.4% and 0.0% using bandwidths of 122 Hz/mm and 488 Hz/mm at 3 T. Dose differences between dCT and CT treatment plans in D-50 at the planning target volume were 0.4% +/- 0.6% and 0.3% +/- 0.5% at 122 and 488 Hz/mm, respectively.

    Conclusions: The overall effect of MRI geometric distortions on data used for RTP was minimal. Shimming over entire imaging volumes decreased distortions, but user-defined subvolume shimming introduced significant errors in nearby organs and should probably be avoided.

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  • 16.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Jonsson, Joakim H.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Medical Radiation Physics, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Quantifying the Effect of 3T Magnetic Resonance Imaging Residual System Distortions and Patient-Induced Susceptibility Distortions on Radiation Therapy Treatment Planning for Prostate Cancer2018In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 100, no 2, p. 317-324Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of magnetic resonance system- and patient-induced susceptibility distortions from a 3T scanner on dose distributions for prostate cancers.

    Methods and Materials: Combined displacement fields from the residual system and patient-induced susceptibility distortions were used to distort 17 prostate patient CT images. VMAT dose plans were initially optimized on distorted CT images and the plan parameters transferred to the original patient CT images to calculate a new dose distribution.

    Results: Maximum residual mean distortions of 3.19 mm at a radial distance of 25 cm and maximum mean patient-induced susceptibility shifts of 5.8 mm were found using the lowest bandwidth of 122 Hz per pixel. There was a dose difference of <0.5% between distorted and undistorted treatment plans. The 90% confidence intervals of the mean difference between the dCT and CT treatment plans were all within an equivalence interval of (−0.5, 0.5) for all investigated plan quality measures.

    Conclusions: Patient-induced susceptibility distortions at high field strengths in closed bore magnetic resonance scanners are larger than residual system distortions after using vendor-supplied 3-dimensional correction for the delineated regions studied. However, errors in dose due to disturbed patient outline and shifts caused by patient-induced susceptibility effects are below 0.5%.

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  • 17.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Quality Assurance for MRI in Radiotherapy: Sensitivity Analysis of Current MethodsManuscript (preprint) (Other academic)
  • 18.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Sensitivity analysis of different quality assurance methods for magnetic resonance imaging in radiotherapy2020In: Physics and Imaging in Radiation Oncology, E-ISSN 2405-6316, Vol. 13, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Background and purpose: There are currently no standard quality assurance (QA) methods for magnetic resonance imaging (MRI) in radiotherapy (RT). This work was aimed at evaluating the ability of two QA protocols to detect common events that affect quality of MR images under RT settings.

    Materials and methods: The American College of Radiology (ACR) MRI QA phantom was repeatedly scanned using a flexible coil and action limits for key image quality parameters were derived. Using an exploratory survey, issues that reduce MR image quality were identified. The most commonly occurring events were introduced as provocations to produce MR images with degraded quality. From these images, detection sensitivities of the ACR MRI QA protocol and a commercial geometric accuracy phantom were determined.

    Results: Machine-specific action limits for key image quality parameters set at mean&#xB1;3&#x3C3;" role="presentation" style="box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative;">mean±3σ were comparable with the ACR acceptable values. For the geometric accuracy phantom, provocations from uncorrected gradient nonlinearity effects and a piece of metal in the bore of the scanner resulted in worst distortions of 22.2 mm and 3.4 mm, respectively. The ACR phantom was sensitive to uncorrected signal variations, electric interference and a piece of metal in the bore of the scanner but could not adequately detect individual coil element failures.

    Conclusions: The ACR MRI QA phantom combined with the large field-of-view commercial geometric accuracy phantom were generally sensitive in identifying some common MR image quality issues. The two protocols when combined may provide a tool to monitor the performance of MRI systems in the radiotherapy environment.

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  • 19.
    Adjeiwaah, Mary
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lundman, Josef A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bylund, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Technical Note: Comparison between simulated and measured B0 field maps of head and neck MRIManuscript (preprint) (Other academic)
  • 20. Adolfsson, Jan
    et al.
    Garmo, Hans
    Varenhorst, Eberhard
    Ahlgren, Göran
    Ahlstrand, Christer
    Andrén, Ove
    Bill-Axelson, Anna
    Bratt, Ola
    Damber, Jan-Erik
    Hellström, Karin
    Hellström, Magnus
    Holmberg, Erik
    Holmberg, Lars
    Hugosson, Jonas
    Johansson, Jan-Erik
    Petterson, Bill
    Törnblom, Magnus
    Widmark, Anders
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005.2007In: Scand J Urol Nephrol, ISSN 0036-5599, Vol. 41, p. 456-477Article in journal (Refereed)
  • 21.
    Adrian, Gabriel
    et al.
    Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden; Division of Oncology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
    Carlsson, Henrik
    Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden; Division of Oncology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
    Kjellén, Elisabeth
    Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden.
    Sjövall, Johanna
    Department of Otorhinolaryngology –Head and Neck Surgery, Skåne University Hospital, Lund University, Lund, Sweden.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden; Department of Clinical Sciences, Medical Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden.
    Gebre-Medhin, Maria
    Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden.
    Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy2022In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 17, no 1, article id 107Article in journal (Refereed)
    Abstract [en]

    Background: The prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT). Methods: Five hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume. Results: The volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume. Conclusions: Outcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.

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  • 22. Adrian, Gabriel
    et al.
    Gebre-Medhin, Maria
    Kjellen, Elisabeth
    Wieslander, Elinore
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Altered fractionation diminishes importance of tumor volume in oropharyngeal cancer: Subgroup analysis of ARTSCAN-trial2020In: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 42, no 8, p. 2099-2105Article in journal (Refereed)
    Abstract [en]

    Background: A large tumor volume negatively impacts the outcome of radiation therapy (RT). Altered fractionation (AF) can improve local control (LC) compared with conventional fractionation (CF). The aim of the present study was to investigate if response to AF differs with tumor volume in oropharyngeal cancer.

    Methods: Three hundred and twenty four patients with oropharyngeal cancer treated in a randomized, phase III trial comparing CF (2 Gy/d, 5 d/wk, 7 weeks, total dose 68 Gy) to AF (1.1 Gy + 2 Gy/d, 5 d/wk, 4.5 weeks, total dose 68 Gy) were analyzed.

    Results: Tumor volume had less impact on LC for patients treated with AF. There was an interaction between tumor volume and fractionation schedule (P = .039). This differential response was in favor of CF for small tumors and of AF for large tumors.

    Conclusion: AF diminishes the importance of tumor volume for local tumor control in oropharyngeal cancer.

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  • 23.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Flygare, Carolina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Remes, Jussi
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eriksson, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Bäckström, David C.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Reliability and validity of visual analysis of [18F]FE-PE2I PET/CT in early Parkinsonian disease2023In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 44, no 5, p. 397-406Article in journal (Refereed)
    Abstract [en]

    Objective: [18F]FE-PE2I (FE-PE2I) is a new radiotracer for dopamine transporter (DAT) imaging with PET. The aim of this study was to evaluate the visual interpretation of FE-PE2I images for the diagnosis of idiopathic Parkinsonian syndrome (IPS). The inter-rater variability, sensitivity, specificity, and diagnostic accuracy for visual interpretation of striatal FE-PE2I compared to [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) was evaluated.

    Methods: Thirty patients with newly onset parkinsonism and 32 healthy controls with both an FE-PE2I and FP-CIT were included in the study. Four patients had normal DAT imaging, of which three did not fulfil the IPS criteria at the clinical reassessment after 2 years. Six raters evaluated the DAT images blinded to the clinical diagnosis, interpreting the image as being ‘normal’ or ‘pathological’, and assessed the degree of DAT-reduction in the caudate and putamen. The inter-rater agreement was assessed with intra-class correlation and Cronbach’s α. For calculation of sensitivity and specificity, DAT images were defined as correctly classified if categorized as normal or pathological by ≥4/6 raters.

    Results: The overall agreement in visual evaluation of the FE-PE2I- and FP-CIT images was high for the IPS patients (α = 0.960 and 0.898, respectively), but lower in healthy controls (FE-PE2I: α = 0.693, FP-CIT: α = 0.657). Visual interpretation gave high sensitivity (both 0.96) but lower specificity (FE-PE2I: 0.86, FP-CIT: 0.63) with an accuracy of 90% for FE-PE2I and 77% for FP-CIT.

    Conclusion: Visual evaluation of FE-PE2I PET imaging demonstrates high reliability and diagnostic accuracy for IPS.

  • 24.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Barkander, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Pelegrina-Hidalgo, Noelia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Gerhardt, Greg A
    Virel, Ana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Noradrenaline is crucial for the substantia nigra dopaminergic cell maintenance2019In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 131, article id 104551Article in journal (Refereed)
    Abstract [en]

    In Parkinson's disease, degeneration of substantia nigra dopaminergic neurons is accompanied by damage on other neuronal systems. A severe denervation is for example seen in the locus coerulean noradrenergic system. Little is known about the relation between noradrenergic and dopaminergic degeneration, and the effects of noradrenergic denervation on the function of the dopaminergic neurons of substantia nigra are not fully understood. In this study, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) was injected in rats, whereafter behavior, striatal KCl-evoked dopamine and glutamate releases, and immunohistochemistry were monitored at 3 days, 3 months, and 6 months. Quantification of dopamine-beta-hydroxylase-immunoreactive nerve fiber density in the cortex revealed a tendency towards nerve fiber regeneration at 6 months. To sustain a stable noradrenergic denervation throughout the experimental timeline, the animals in the 6-month time point received an additional DSP4 injection (2 months after the first injection). Behavioral examinations utilizing rotarod revealed that DSP4 reduced the time spent on the rotarod at 3 but not at 6 months. KCl-evoked dopamine release was significantly increased at 3 days and 3 months, while the concentrations were normalized at 6 months. DSP4 treatment prolonged both time for onset and reuptake of dopamine release over time. The dopamine degeneration was confirmed by unbiased stereology, demonstrating significant loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Furthermore, striatal glutamate release was decreased after DSP4. In regards of neuroinflammation, reactive microglia were found over the substantia nigra after DSP4 treatment. In conclusion, long-term noradrenergic denervation reduces the number of dopaminergic neurons in the substantia nigra and affects the functionality of the nigrostriatal system. Thus, locus coeruleus is important for maintenance of nigral dopaminergic neurons.

  • 25.
    Aglago, Elom K.
    et al.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Fedirko, Veronika
    Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, TX, Houston, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States.
    Hughes, David J.
    Cancer Biology and Therapeutics Group (CBT), Conway Institute, School of Biomolecular and Biomedical Science (SBBS), University College Dublin, Dublin, Ireland.
    Fournier, Agnes
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
    Jakszyn, Paula
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
    Freisling, Heinz
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Overvad, Kim
    Department of Public Health, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Section of Environmental Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Kyrø, Cecilie
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Boutron-Ruault, Marie-Christine
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
    Rothwell, Joseph A.
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
    Severi, Gianluca
    Centre de Recherche en Epidémiologie et Santé des Populations, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Institut Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, Florence, Italy.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer research Center (DKFZ), Heidelberg, Germany.
    Srour, Bernard
    Division of Cancer Epidemiology, German Cancer research Center (DKFZ), Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
    Wittenbecher, Clemens
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States; German Center for Diabetes Research (DZD), Neuherberg, Germany.
    Palli, Domenico
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, ISPRO, Florence, Italy.
    Sieri, Sabina
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian, Milano, Italy.
    Pasanisi, Fabrizio
    Internal Medicine and Clinical Nutrition Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy.
    Tumino, Rosario
    Hyblean Association for Epidemiological Research, AIRE-ONLUS, Ragusa, Italy.
    Ricceri, Fulvio
    Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Unit of Epidemiology, Regional Health Service, TO, Grugliasco, Italy.
    Bueno-de-Mesquita, Bas
    Former senior scientist, Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven, Netherlands.
    Derksen, Jeroen W. G.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Skeie, Guri
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Jensen, Torill Enget
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Lukic, Marko
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Amiano, Pilar
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Spain; Biodonostia Health Research Institute, Epidemiology and Public Health Area, San Sebastián, Spain.
    Colorado-Yohar, Sandra
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
    Barricarte, Aurelio
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Ericson, Ulrika
    Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Papier, Keren
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Knuppel, Anika
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Casagrande, Corinne
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Huybrechts, Inge
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Heath, Alicia K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
    Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study2023In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 128, p. 1529-1540Article in journal (Refereed)
    Abstract [en]

    Background: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.

    Methods: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.

    Results: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).

    Conclusions: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

  • 26. Aglago, Elom K.
    et al.
    Huybrechts, Inge
    Murphy, Neil
    Casagrande, Corinne
    Nicolas, Genevieve
    Pischon, Tobias
    Fedirko, Veronika
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Fournier, Agnès
    Katzke, Verena
    Kühn, Tilman
    Olsen, Anja
    Tjønneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Lasheras, Cristina
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Huerta, José Maria
    Ardanaz, Eva
    Perez-Cornago, Aurora
    Trichopoulou, Antonia
    Karakatsani, Anna
    Martimianaki, Georgia
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    May, Anne
    Derksen, Jeroen W. G.
    Hellstrand, Sophie
    Ohlsson, Bodil
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Skeie, Guri
    Brustad, Magritt
    Weiderpass, Elisabete
    Cross, Amanda J.
    Ward, Heather
    Riboli, Elio
    Norat, Teresa
    Chajes, Veronique
    Gunter, Marc J.
    Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort2020In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, p. 654-666Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

    RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026).

    CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

  • 27.
    Aglago, Elom K.
    et al.
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Kim, Andre
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Qu, Conghui
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Evangelou, Marina
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Ren, Yu
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
    Morrison, John
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Albanes, Demetrius
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, Liberia.
    Arndt, Volker
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Barry, Elizabeth L.
    Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
    Baurley, James W.
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Berndt, Sonja I.
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, Liberia.
    Bien, Stephanie A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Bishop, D Timothy
    Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
    Bouras, Emmanouil
    Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Brenner, Hermann
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Buchanan, Daniel D.
    Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, VIC, Parkville, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, VIC, Parkville, Australia; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, VIC, Parkville, Australia.
    Budiarto, Arif
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
    Carreras-Torres, Robert
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.
    Casey, Graham
    Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Cenggoro, Tjeng Wawan
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Chan, Andrew T.
    Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Chang-Claude, Jenny
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
    Chen, Xuechen
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
    Conti, David V.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Devall, Matthew
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Diez-Obrero, Virginia
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
    Dimou, Niki
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Drew, David
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States.
    Figueiredo, Jane C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, CA, Los Angeles, United States.
    Gallinger, Steven
    Lunenfeld Tanenbaum Research Institute, University of Toronto, Mount Sinai Hospital, ON, Toronto, Canada.
    Giles, Graham G.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Clayton, Australia.
    Gruber, Stephen B.
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center.
    Gsur, Andrea
    Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Hampel, Heather
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hidaka, Akihisa
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Harrison, Tabitha A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Hoffmeister, Michael
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Huyghe, Jeroen R.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Jenkins, Mark A.
    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
    Jordahl, Kristina
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Joshi, Amit D.
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States.
    Kawaguchi, Eric S.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Keku, Temitope O.
    Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United States.
    Kundaje, Anshul
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Larsson, Susanna C.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Marchand, Loic Le
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lewinger, Juan Pablo
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Li, Li
    Department of Family Medicine, University of Virginia, VA, Charlottesville, United States.
    Lynch, Brigid M.
    Cancer Epidemiology Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
    Mahesworo, Bharuno
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Mandic, Marko
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
    Obón-Santacana, Mireia
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Moreno, Victor
    ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
    Murphy, Neil
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Nan, Hongmei
    Department of Epidemiology, Richard M. Fairbanks School of Public Health, IN, Indianapolis, United States; IU Melvin and Bren Simon Cancer Center, Indiana University, IN, Indianapolis, United States.
    Nassir, Rami
    Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia.
    Newcomb, Polly A.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Ogino, Shuji
    Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, Boston, United States.
    Ose, Jennifer
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Pai, Rish K.
    Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, AZ, Scottsdale, United States.
    Palmer, Julie R.
    Department of Medicine, Boston University School of Medicine, Slone Epidemiology Center, Boston University, MA, Boston, United States.
    Papadimitriou, Nikos
    Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Pardamean, Bens
    Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
    Peoples, Anita R.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    Platz, Elizabeth A.
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
    Prentice, Ross L.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Rennert, Gad
    Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
    Ruiz-Narvaez, Edward
    Department of Nutritional Sciences, University of Michigan School of Public Health, MI, Ann Arbor, United States.
    Sakoda, Lori C.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Division of Research, Kaiser Permanente Northern California, CA, Oakland, United States.
    Scacheri, Peter C.
    Department of Genetics and Genome Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Schmit, Stephanie L.
    Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States.
    Schoen, Robert E.
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Shcherbina, Anna
    Department of Genetics, Stanford University, CA, Stanford, United States; Department of Computer Science, Stanford University, CA, Stanford, United States.
    Slattery, Martha L.
    Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States.
    Stern, Mariana C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Su, Yu-Ru
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Tangen, Catherine M.
    SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Thibodeau, Stephen N.
    Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, Rochester, United States.
    Thomas, Duncan C.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Tian, Yu
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China.
    Ulrich, Cornelia M.
    Huntsman Cancer Institute, UT, Salt Lake City, United States; Department of Population Health Sciences, University of Utah, UT, Salt Lake City, United States.
    van Duijnhoven, Franzel Jb
    Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Visvanathan, Kala
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, Liberia.
    Vodicka, Pavel
    Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
    Wang, Jun
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    White, Emily
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Woods, Michael O.
    Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
    Wu, Anna H.
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Zemlianskaia, Natalia
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Hsu, Li
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Gauderman, W James
    Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington School of Public Health, WA, Seattle, United States.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
    Campbell, Peter T.
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States.
    A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk2023In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 83, no 15, p. 2572-2583Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.

    SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

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  • 28. Aglago, Elom K.
    et al.
    Mayén, Ana-Lucia
    Knaze, Viktoria
    Freisling, Heinz
    Fedirko, Veronika
    Hughes, David J.
    Jiao, Li
    Eriksen, Anne Kirstine
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Rothwell, Joseph A.
    Severi, Gianluca
    Kaaks, Rudolf
    Katzke, Verena
    Schulze, Matthias B.
    Birukov, Anna
    Palli, Domenico
    Sieri, Sabina
    Santucci de Magistris, Maria
    Tumino, Rosario
    Ricceri, Fulvio
    Bueno-de-Mesquita, Bas
    Derksen, Jeroen W. G.
    Skeie, Guri
    Gram, Inger Torhild
    Sandanger, Torkjel
    Quirós, J. Ramón
    Luján-Barroso, Leila
    Sánchez, Maria-Jose
    Amiano, Pilar
    Chirlaque, María-Dolores
    Gurrea, Aurelio Barricarte
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Manjer, Jonas
    Perez-Cornago, Aurora
    Weiderpass, Elisabete
    Gunter, Marc J.
    Heath, Alicia K.
    Schalkwijk, Casper G.
    Jenab, Mazda
    Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study2021In: Nutrients, E-ISSN 2072-6643, Vol. 13, no 9, article id 3132Article in journal (Refereed)
    Abstract [en]

    Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

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  • 29. Aglago, Elom K.
    et al.
    Rinaldi, Sabina
    Freisling, Heinz
    Jiao, Li
    Hughes, David J.
    Fedirko, Veronika
    Schalkwijk, Casper G.
    Weiderpass, Elisabete
    Dahm, Christina C.
    Overvad, Kim
    Eriksen, Anne Kirstine
    Kyrø, Cecilie
    Boutron-Ruault, Marie-Christine
    Rothwell, Joseph A.
    Severi, Gianluca
    Katzke, Verena
    Kühn, Tilman
    Schulze, Matthias B.
    Aleksandrova, Krasimira
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Naccarati, Alessio
    Bueno-de-Mesquita, Bas
    van Gils, Carla H.
    Sandanger, Torkjel M.
    Gram, Inger T.
    Skeie, Guri
    Quirós, J. Ramón
    Jakszyn, Paula
    Sánchez, Maria-Jose
    Amiano, Pilar
    Huerta, José María
    Ardanaz, Eva
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Odontology.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Perez-Cornago, Aurora
    Mayén, Ana-Lucia
    Cordova, Reynalda
    Gunter, Marc J.
    Vineis, Paolo
    Cross, Amanda J.
    Riboli, Elio
    Jenab, Mazda
    Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort2021In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, no 1, p. 182-192Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.

    METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.

    RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).

    CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.

    IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

  • 30.
    Aglund, Kristina
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Rauvala, Marita
    Puistola, Ulla
    Ångström, Tord
    Umeå University, Faculty of Medicine, Medical Biosciences.
    Turpeenniemi-Hujanen, Taina
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Stendahl, Ulf
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage2004In: Gynecol Oncol, ISSN 0090-8258, Vol. 94, no 3, p. 699-704Article in journal (Refereed)
  • 31. Agudo, Antonio
    et al.
    Cayssials, Valerie
    Bonet, Catalina
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Affret, Aurélie
    Fagherazzi, Guy
    Katzke, Verena
    Schübel, Ruth
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Ricceri, Fulvio
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Peeters, Petra H.
    Weiderpass, Elisabete
    Skeie, Guri
    Nøst, Theresa H.
    Lasheras, Cristina
    Rodríguez-Barranco, Miguel
    Amiano, Pilar
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Ohlsson, Bodil
    Dias, Joana A.
    Nilsson, Lena M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Myte, Robin
    Khaw, Kay-Tee
    Perez-Cornago, Aurora
    Gunter, Marc
    Huybrechts, Inge
    Cross, Amanda J.
    Tsilidis, Kostas
    Riboli, Elio
    Jakszyn, Paula
    Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2018In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 107, no 4, p. 607-616Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.

  • 32. Ahlqvist-Rastad, Jane
    et al.
    Albertsson, Maria
    Bergh, Jonas
    Birgegård, Gunnar
    Johansson, Peter
    Jonsson, Bertil
    Kjellén, Elisabeth
    Påhlman, Sven
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Österborg, Anders
    Erythropoietin therapy and cancer related anaemia: updated Swedish recommendations.2007In: Med Oncol, ISSN 1357-0560, Vol. 24, no 3, p. 267-272Article in journal (Refereed)
  • 33. Ahlén Bergman, Emma
    et al.
    Hartana, Ciputra Adijaya
    Johansson, Markus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Sundsvall Hospital, Sundsvall, Sweden..
    Linton, Ludvig B
    Berglund, Sofia
    Hyllienmark, Martin
    Lundgren, Christian
    Holmström, Benny
    Palmqvist, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgery, Urology Section, Östersund County Hospital, Östersund, Sweden.
    Hansson, Johan
    Alamdari, Farhood
    Huge, Ylva
    Aljabery, Firas
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Winerdal, Malin E
    Krantz, David
    Zirakzadeh, A. Ali
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Unit of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Marits, Per
    Sjöholm, Louise K
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Winqvist, Ola
    Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients2018In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 102Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.

    RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.

    CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.

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  • 34.
    Ahmed, Maghfoor
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Antibiotikaanvändning före diagnos och överlevnad vidkolorektalcancer stadium IV.2022Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 35.
    Akhtari, Mohammad Mehdi
    Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    3D Structural similarity check between CT and SCT2014Independent thesis Advanced level (degree of Master (Two Years)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of the current work was to develop and test a method for comparing the geometrical representation of a patient using computed tomography (CT), and CT like images derived from magnetic resonance images (MRI). It would be beneficial to use MRI alone for both target delineation and treatment planning to save time and costs. This was first investigated in Umea university Hospital by introducing substitute computed tomography (SCT) obtained from MRI images and which can be used as CT equivalent information. The data that is used in this report are from five patients with intracranial tumors; A MATLAB code has been developed to compare DDRs based on s-CT data with CT based DRR’s for these five patients.

  • 36. Aksnessaether, Bjorg Y.
    et al.
    Myklebus, Tor Age
    Solberg, Arne
    Klepp, Olbjorn H.
    Skovlund, Eva
    Hoff, Solveig Roth
    Fossa, Sophie D.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lund, Jo-Asmund
    In Reply to Sari et al2020In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 107, no 2, p. 388-389Article in journal (Refereed)
  • 37. Aksnessaether, Bjorg Y.
    et al.
    Myklebust, Tor Age
    Solberg, Arne
    Klepp, Olbjorn H.
    Skovlund, Eva
    Hoff, Solveig Roth
    Fossa, Sophie D.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lund, Jo-Asmund
    Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial2020In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 106, no 4, p. 706-714Article in journal (Refereed)
    Abstract [en]

    Background: Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death.

    Methods and Materials: The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC.

    Results: Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65).

    Conclusions: Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.

  • 38.
    Aksu, Fatih
    et al.
    Humanitas University, Department of Biomedical Sciences, Milan, Italy.
    Gelardi, Fabrizia
    Humanitas University, Department of Biomedical Sciences, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy.
    Chiti, Arturo
    Humanitas University, Department of Biomedical Sciences, Milan, Italy; IRCCS Humanitas Research Hospital, Milan, Italy.
    Soda, Paolo
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Humanitas University, Department of Biomedical Sciences, Milan, Italy; Campus Bio-Medico University of Rome, Research Unit of Computer Systems and Bioinformatics, Rome, Italy.
    Early Experiences on using Triplet Networks for Histological Subtype Classification in Non-Small Cell Lung Cancer2023In: 2023 IEEE 36th International Symposium on Computer-Based Medical Systems (CBMS): Proceedings / [ed] João Rafael Almeida; Myra Spiliopoulou; Jose Alberto Benitez Andrades; Giuseppe Placidi; Alejandro Rodríguez González; Rosa Sicilia; Bridget Kane, IEEE, 2023, p. 832-837Conference paper (Refereed)
    Abstract [en]

    Lung cancer has the highest mortality rate among tumours and an accurate pathological assessment is crucial to deliver personalized treatments to patients. The gold standard for pathological assessment requires invasive procedures, which are not always possible and might cause clinical complications. Therefore, in the last years, efforts have been directed towards the development of machine and deep learning approaches for virtual biopsy, which leverage routinely collected CT scans. However, in many cases, the available datasets are limited in size, an issue that limits the training of any model. In this paper, we investigate if triplet networks can cope with this limitation: they are a class of neural networks that uses the same weights while working in tandem on three different input vectors to minimize the loss function. In particular, on a dataset including 87 CT scans collected from patients suffering from non-small cell lung cancer, we experimentally compare triplet networks against plain deep networks when performing histological subtype classification. The results show that the former outperforms the latter in almost all experiments.

  • 39. Alakurtti, Kati
    et al.
    Johansson, Jarkko J.
    Joutsa, Juho
    Laine, Matti
    Backman, Lars
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rinne, Juha O.
    Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding: study with [C-11]raclopride and high-resolution PET2015In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 35, no 7, p. 1199-1205Article in journal (Refereed)
    Abstract [en]

    We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.

  • 40.
    Alamdari, Farhood Iranparvar
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry. Klinisk kemi.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
    Angiogenesis and other markers for prediction of survival in metastatic renal cell carcinoma.2007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 1, p. 5-9Article in journal (Refereed)
  • 41.
    Ala-Prinkkilä, Aleksi
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Explorativ analys av motorisk aktivitet under sömn på3-åriga barn2022Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 42.
    Albano, Amanda
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Gustavsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Echocardio-variability - Low and high frequency beat-to-beat variability in echocardiographic signals2013In: Computing in Cardiology 2013, 2013, p. 767-770, article id 6713490Conference paper (Refereed)
    Abstract [en]

    Measurement signals originating from the cardiovascular system are known to comprise oscillating components and beat-to-beat variability, e.g., heart-rate variability and blood pressure variability. In clinical echocardiographic procedures, typically only a few cardiac cycles are acquired. This pilot study analyses the beat-to-beat variability of echocardiographic variables (echocardio-variability) in minute long acquisitions. 

  • 43. Aleksandrova, Krasimira
    et al.
    Chuang, Shu-Chun
    Boeing, Heiner
    Zuo, Hui
    Tell, Grethe S
    Pischon, Tobias
    Jenab, Mazda
    Bueno-de-Mesquita, Bas
    Vollset, Stein Emil
    Midttun, Øivind
    Ueland, Per Magne
    Fedirko, Veronika
    Johansson, Mattias
    Weiderpass, Elisabete
    Severi, Gianluca
    Racine, Antoine
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Kühn, Tilman
    Tjønneland, Anne
    Overvad, Kim
    Quirós, J Ramón
    Jakszyn, Paula
    Sánchez, María-José
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Travis, Ruth C
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Panico, Salvatore
    May, Anne M
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kong, So Yeon J
    Freisling, Heinz
    Gunter, Marc J
    Lu, Yunxia
    Cross, Amanda J
    Riboli, Elio
    Vineis, Paolo
    A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk2015In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, no 4, article id djv010Article in journal (Refereed)
    Abstract [en]

    Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

  • 44. Aleksandrova, Krasimira
    et al.
    Jenab, Mazda
    Bueno-de-Mesquita, H. Bas
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    van Duijnhoven, Franzel J. B.
    Jansen, Eugene
    Rinaldi, Sabina
    Romieu, Isabelle
    Ferrari, Pietro
    Murphy, Neil
    Gunter, Marc J.
    Riboli, Elio
    Westhpal, Sabine
    Overvad, Kim
    Tjonneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Trichopoulou, Antonia
    Bamia, Christina
    Orfanos, Philippos
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Duell, Eric J.
    Molina-Montes, Esther
    Ramon Quiros, J.
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Pischon, Tobias
    Boeing, Heiner
    Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)2014In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, no 4, p. 261-275Article in journal (Refereed)
    Abstract [en]

    A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.

  • 45. Aleksandrova, Krasimira
    et al.
    Jenab, Mazda
    Leitzmann, Michael
    Bueno-de-Mesquita, Bas
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Rinaldi, Sabina
    Freisling, Heinz
    Carayol, Marion
    Pischon, Tobias
    Drogan, Dagmar
    Weiderpass, Elisabete
    Jakszyn, Paula
    Overvad, Kim
    Dahm, Christina C.
    Tjonneland, Anne
    Bouton-Ruault, Marie-Christine
    Kuehn, Tilman
    Peppa, Eleni
    Valanou, Elissavet
    La Vecchia, Carlo
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Agnoli, Claudia
    Tumino, Rosario
    May, Anne
    van Vulpen, Jonna
    Borch, Kristin Benjaminsen
    Oyeyemi, Sunday Oluwafemi
    Ramon Quiros, J.
    Bonet, Catalina
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Navarro, Carmen
    Barricarte, Aurelio
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Assi, Nada
    Ward, Heather A.
    Aune, Dagfinn
    Riboli, Elio
    Boeing, Heiner
    Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort2017In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, no 6, p. 1823-1835Article in journal (Refereed)
    Abstract [en]

    There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand<yen>91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.

  • 46. Aleksandrova, Krasimira
    et al.
    Pischon, Tobias
    Jenab, Mazda
    Bueno-de-Mesquita, H Bas
    Fedirko, Veronika
    Norat, Teresa
    Romaguera, Dora
    Knüppel, Sven
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Kaaks, Rudolf
    Li, Kuanrong
    Tjønneland, Anne
    Overvad, Kim
    Quirós, José Ramón
    Buckland, Genevieve
    Sánchez, María José
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Bradbury, Kathryn E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Siersema, Peter D
    Peeters, Petra HM
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ericson, Ulrika
    Ohlsson, Bodil
    Weiderpass, Elisabete
    Skeie, Guri
    Borch, Kristin
    Rinaldi, Sabina
    Romieu, Isabelle
    Kong, Joyce
    Gunter, Marc J
    Ward, Heather A
    Riboli, Elio
    Boeing, Heiner
    Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study2014In: BMC Medicine, E-ISSN 1741-7015, Vol. 12, no 1, p. 168-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

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  • 47. Aleksandrova, Krasimira
    et al.
    Reichmann, Robin
    Kaaks, Rudolf
    Jenab, Mazda
    Bueno-de-Mesquita, H. Bas
    Dahm, Christina C.
    Eriksen, Anne Kirstine
    Tjonneland, Anne
    Artaud, Fanny
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Husing, Anika
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Panico, Salvatore
    Masala, Giovanna
    Grioni, Sara
    Sacerdote, Carlotta
    Tumino, Rosario
    Elias, Sjoerd G.
    May, Anne M.
    Borch, Kristin B.
    Sandanger, Torkjel M.
    Skeie, Guri
    Sanchez, Maria-Jose
    Huerta, Jose Maria
    Sala, Nuria
    Gurrea, Aurelio Barricarte
    Quiros, Jose Ramon
    Amiano, Pilar
    Berntsson, Jonna
    Drake, Isabel
    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).
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Key, Tim
    Weiderpass, Elisabete
    Aglago, Elom K.
    Cross, Amanda J.
    Tsilidis, Konstantinos K.
    Riboli, Elio
    Gunter, Marc J.
    Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score2021In: BMC Medicine, E-ISSN 1741-7015, Vol. 19, no 1, article id 1Article in journal (Refereed)
    Abstract [en]

    Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population.

    Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed.

    Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)).

    Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.

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  • 48.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Handheld ECG in analysis of arrhythmia and heart rate variability in children with Fontan circulation2014In: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 47, no 3, p. 374-382Article in journal (Refereed)
    Abstract [en]

    Background: Our aim was to evaluate the intermittent use of a handheld ECG system for detecting silent arrhythmias and cardiac autonomic dysfunction in children with univentricular hearts. Methods: Twenty-seven patients performed intermittent ECG recordings with handheld devices during a 14-day period. A manual arrhythmia analysis was performed. We analyzed heart rate variability (HRV) using scatter plots of all interbeat intervals (Poincare plots) from the total observation period. Reference values of HRV indices were determined from Holter-ECGs in 41 healthy children. Results: One asymptomatic patient had frequent ventricular extra systoles. Another patient had episodes with supraventricular tachycardia (with concomitant palpitations). Seven patients showed reduced HRV. Conclusions: Asymptomatic arrhythmia was detected in one patient. The proposed method for pooling of intermittent recordings from handheld or similar devices may be used for detection of arrhythmias as well as for cardiac autonomic dysfunction.

  • 49.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Strömvall-Larsson, Eva
    Division of Cardiology, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Berggren, Håkan
    Division of Cardiothoracic Surgery, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Hanseus, Katarina
    Department of Paediatrics, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Johansson, Sune
    Paediatric Cardiac Surgical Unit, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Heart rate variability in children with fontan circulation: lateral tunnel and extracardiac conduit2012In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 33, no 2, p. 307-315Article in journal (Refereed)
    Abstract [en]

    The technique in Fontan surgery has developed from the lateral tunnel (LT) toward the extracardiac conduit (EC) used to reduce long-term complications such as atrial arrhythmia and sinus node dysfunction. Heart rate variability (HRV) examines cardiac nervous activity controlling the sinus node. This study aimed to investigate HRV in a cohort of children with univentricular hearts, focusing on the relation between HRV and surgical procedure. For 112 children with Fontan circulation, HRV was analyzed using power spectral analysis. Spectral power was determined in three regions: very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) regions. Patients were compared with 66 healthy controls subject. Patients with LT were compared with patients who had EC. The children with Fontan circulation showed a significantly reduced HRV including total power (P < 0.0001), VLF (P < 0.0001), LF (P < 0.0001), and HF (P = 0.001) compared with the control subjects. The LT and EC patients did not differ significantly. Reduced HRV was found in both the LT and EC patients. In terms of HRV reduction, EC was not superior to LT.

  • 50.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sunnegårdh, Jan
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Hanséus, Katarina
    Department of Clinical Sciences Lund, Children Heart Center, Skåne University Hospital, Lund University, Lund, Sweden.
    Strömvall Larsson, Eva
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Nygren, Anders
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Dalén, Magnus
    Department of Molecular Medicine and Surgery, Department of Cardiac Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Berggren, Håkan
    Department of Pediatric Cardiac Surgery, Children's Heart Center, The Queen Silvia Children's Hospital, Gothenburg , Sweden.
    Johansson Ramgren, Jens
    Department of Pediatric Cardiac Surgery, Children´s Heart Center, Skånes University Hospital Lund, Sweden.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Pacemaker treatment after Fontan surgery: a Swedish national study2019In: Congenital Heart Disease, ISSN 1747-079X, E-ISSN 1747-0803, Vol. 14, no 4, p. 582-589Article in journal (Refereed)
    Abstract [en]

    Objective: Fontan surgery is performed in children with univentricular heart defects. Previous data regarding permanent pacemaker implantation frequency and indications in Fontan patients are limited and conflicting. We examined the prevalence of and risk factors for pacemaker treatment in a consecutive national cohort of patients after Fontan surgery in Sweden.

    Methods: We retrospectively reviewed all Swedish patients who underwent Fontan surgery from 1982 to 2017 (n = 599).

    Results: After a mean follow‐up of 12.2 years, 13% (78/599) of the patients with Fontan circulation had received pacemakers. Patients operated with the extracardiac conduit (EC) type of total cavopulmonary connection had a significantly lower prevalence of pacemaker implantation (6%) than patients with lateral tunnel (LT; 17%). Mortality did not differ between patients with (8%) and without pacemaker (5%). The most common pacemaker indication was sinus node dysfunction (SND) (64%). Pacemaker implantation due to SND was less common among patients with EC. Pacemaker implantation was significantly more common in patients with mitral atresia (MA; 44%), double outlet right ventricle (DORV; 24%) and double inlet left ventricle (DILV; 20%). In contrast, patients with pulmonary atresia with intact ventricular septum and hypoplastic left heart syndrome were significantly less likely to receive a pacemaker (3% and 6%, respectively).

    Conclusions: Thirteen percent of Fontan patients received a permanent pacemaker, most frequently due to SND. EC was associated with a significantly lower prevalence of pacemaker than LT. Permanent pacemaker was more common in patients with MA, DORV, and DILV.

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