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  • 1651.
    Zachariadis, V
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Gauffin, F
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Kuchinskaya, E
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Heyman, M
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Schoumans, J
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Blennow, E
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Gustafsson, B
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Barbany, G
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Ehrencrona, H
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Cavelier, L
    Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Palmqvist, L
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lönnerholm, G
    Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden.
    Nordenskjöld, M
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Johansson, B
    Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordgren, A
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial2011In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 25, no 4, p. 622-628Article in journal (Refereed)
    Abstract [en]

    The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses-in a three-step manner-using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

  • 1652. Zachariadis, V.
    et al.
    Schoumans, J.
    Ofverholm, I.
    Barbany, G.
    Halvardsson, E.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Johansson, B.
    Nordenskjold, M.
    Nordgren, A.
    Detecting dic(9;20)(p13.2;p11.2)-positive B-cell precursor acute lymphoblastic leukemia in a clinical setting using fluorescence in situ hybridization2014In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 28, no 1, p. 196-198Article in journal (Refereed)
  • 1653.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Biological effects of high energy radiation and ultra high dose rates1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Recently a powerful electron accelerator, 50 MeV race-track microtron, has been taken into clinical use. This gives the opportunity to treat patients with higher x-ray and electron energies than before. Furthermore, treatments can be performed were the entire fractional dose can be delivered in parts of a second.

    The relative biological effectiveness (RBE) of high energy photons (up to 50 MV) was studied in vitro and in vivo. Oxygen enhancement ratio (OER) of 50 MV photons and RBE of 50 MeV electrons were investigated in vitro. Single-fraction experiments, in vitro, using V-79 Chinese hamster fibroblasts showed an RBE for 50 MV x-rays of approximately 1.1 at surviving fraction 0.01, with reference to the response to 4 MV x- rays. No significant difference in OER could be demonstrated. Fractionation experiments were carried out to establish the RBE at the clinically relevant dose level, 2 Gy. The RBE calculated for the 2 Gy/fraction experiments was 1.17. The RBEs for 20 MV x-rays and 50 MeV electrons were equal to one. In order to investigate the validity of these results, the jejunal crypt microcolony assay in mice was used to determine the RBE of 50 MV x-rays. The RBE for 50 MV x-rays in this case was estimated to be 1.06 at crypt surviving fraction 0.1. Photonuclear processes are proposed as one possible explanation to the higher RBE for 50 MV x-rays.

    Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. With the aim of investigating whether a difference in effect between irradiation at high dose rates and at conventional dose rates could be verified, pulsed 50 MeV electrons from a clinical accelerator were used for experiments with ultra high dose rates (mean dose rate: 3.8 x 10^ Gy/s) in comparison to conventional (mean dose rate: 9.6 x 10"^ Gy/s). V-79 cells were irradiated in vitro under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed for ultra high dose rates compared to conventional dose rates.

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data are dependent on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. This study shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes at the intracellular level.

  • 1654.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Radiobiological Cell-survival Models: a Methodological Overview1992In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 31, no 4, p. 433-441Article in journal (Refereed)
    Abstract [en]

    A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The, choice of cell survival and dose-response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data depend on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. The present overview shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes and repair processes at the intracellular level.

  • 1655.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Johansson, B.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östbergh, Peter
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Relative Biological Effectiveness and Oxygen Enhancement Ratio of 50 MV X-rays1989In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 28, no 4, p. 529-535Article in journal (Refereed)
  • 1656.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östbergh, Peter
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Relative Biological Effectiveness of High-energy Photons (up tO 50-MV) and Electrons (50-MeV)1991In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 128, no 2, p. 192-196Article in journal (Refereed)
  • 1657.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Relative biological effectiveness of 50-MV X-rays on jejunal crypt survival in vivo1992In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 132, no 1, p. 112-114Article in journal (Refereed)
    Abstract [en]

    Earlier in vitro studies of relative biological effectiveness (RBE) of 50-MV X rays show an RBE of approximately 1.1 compared to 4 MV. No difference in RBE has been found for 20-MV X rays or 50-MeV electrons. The higher RBE for 50 MV can be explained to some extent by the small high linear energy transfer contribution from photonuclear reactions at high X-ray energies. To investigate the validity of the results in vitro, a study of the RBE of 50-MV X rays has been performed in vivo using the jejunal crypt microcolony assay in mice. The reference radiation used in this case was 20-MV X rays. The results confirm the earlier in vitro studies. The RBE for 50-MV X rays was estimated to be 1.06, calculated as the ratio between the slopes of the response curves.

  • 1658.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kjellén, Elisabeth
    Söderström, Karin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brun, Eva
    Nyman, Jan
    Friesland, Signe
    Reizenstein, Johan
    Sjodin, Helena
    Ekberg, Lars
    Lödén, Britta
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ask, Anders
    Wickart-Johansson, Gun
    Lewin, Freddi
    Björk-Eriksson, Thomas
    Lundin, Erik
    Dalianis, Tina
    Wennerberg, Johan
    Johansson, Karl-Axel
    Nilsson, Per
    Mature results from a Swedish comparison study of conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial2015In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 117, no 1, p. 99-105Article in journal (Refereed)
    Abstract [en]

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

  • 1659.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nilsson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Kjellén, Elisabeth
    Skåne University Hospital, Lund and Malmö, Sweden.
    Johansson, Karl-Axel
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Modig, Hans
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brun, Eva
    Skåne University Hospital, Lund and Malmö, Sweden.
    Nyman, Jan
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Friesland, Signe
    Karolinska University Hospital, Stockholm, Sweden.
    Reizenstein, Johan
    Örebro University Hospital, Örebro, Sweden.
    Sjödin, Helena
    Karolinska University Hospital, Stockholm, Sweden.
    Ekberg, Lars
    Skåne University Hospital, Lund and Malmö, Sweden.
    Lödén, Britta
    Karlstad Central Hospital, Karlstad, Sweden.
    Mercke, Claes
    Karolinska University Hospital, Stockholm, Sweden.
    Fernberg, Jan-Olof
    Karolinska University Hospital, Stockholm, Sweden.
    Franzén, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ask, Anders
    Skåne University Hospital, Lund and Malmö, Sweden.
    Persson, Essie
    Örebro University Hospital, Örebro, Sweden.
    Wickart-Johansson, Gun
    Karolinska University Hospital, Stockholm, Sweden.
    Lewin, Freddi
    Karolinska University Hospital, Stockholm, Sweden.
    Wittgren, Lena
    Skåne University Hospital, Lund and Malmö, Sweden.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björk-Eriksson, Thomas
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN study2011In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 100, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

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

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

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

     

  • 1660.
    Zackrisson, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation biology.
    Nyström, U. Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Östbergh, Peter
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Biological Response, in vitro, to Pulsed High-dose Rate Electrons from a Clinical Accelerator1991In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 30, no 6, p. 747-751Article in journal (Refereed)
    Abstract [en]

    Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. The aim of this study was to establish whether a difference between irradiation at high dose rates and at more conventional dose rates could be verified. Pulsed 50 MeV electrons from a clinical accelerator were used both for the high dose rate experiments (mean dose rate: 3.8 x 10(2) Gy/s) and the reference experiments (mean dose rate: 9.6 x 10(-2) Gy/s). In this study V-79 cells were irradiated in vitro. The experiments were carried out under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed at the different dose rates investigated.

  • 1661. Zainuddin, Norafiza
    et al.
    Kanduri, Meena
    Berglund, Mattias
    Lindell, Monica
    Amini, Rose-Marie
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sundström, Christer
    Enblad, Gunilla
    Rosenquist, Richard
    Quantitative evaluation of p16(INK4a) promoter methylation using pyrosequencing in de novo diffuse large B-cell lymphoma2011In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 35, no 4, p. 438-443Article in journal (Refereed)
    Abstract [en]

    The p16INK4a tumor suppressor gene can be inactivated by a variety of events including promoter hypermethylation. In diffuse large B-cell lymphoma (DLBCL), p16INK4a methylation has been associated with advanced disease stage and higher IPI. The prognostic impact of p16INK4a methylation in DLBCL remains unclear; however, it has been suggested to correlate with inferior outcome. To further investigate the clinical impact of p16INK4a methylation in DLBCL, promoter methylation of this gene was assessed quantitatively by pyrosequencing. Forty-two of 113 (37%) DLBCL patients with methylation level above 5% were categorized as methylated and subsequently divided into low, intermediate and high methylation categories. Overall, no association was shown between the extent of p16INK4a methylation and patients' clinical characteristics, except disease stage (P=0.049). Moreover, we could not reveal any impact of p16INK4a methylation on lymphoma-specific survival. Although >25% of p16INK4a methylation correlated with a better progression-free survival (P=0.048) in patients <65 years old, the significance of this finding, if any, needs to be further investigated. In conclusion, our finding questions the role of p16INK4a promoter methylation as a negative prognostic factor in DLBCL.

  • 1662. Zakeri, K.
    et al.
    Rotolo, F.
    Lacas, B.
    Vitzthum, L. K.
    Le, Q-TX.
    Gregoire, V.
    Overgaard, J.
    Tobias, J.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Parmar, M. K.
    Burtness, B. A.
    Ghi, M. G.
    Sanguineti, G.
    O'Sullivan, B.
    Fortpied, C.
    Bourhis, J.
    Shen, H.
    Harris, J.
    Pignon, J-P
    Mell, L. K.
    Predictor of effectiveness of treatment intensification on overall survival in head and neck cancer (HNC)2018In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29Article in journal (Other academic)
  • 1663. Zalewski, K.
    et al.
    Lindemann, K.
    Halaska, M.
    Zapardiel, I.
    Laky, R.
    Chereau, E.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Polterauer, S.
    Suhin, V.
    Dursun, P.
    A CALL FOR NEW COMMUNICATION CHANNELS FOR EUROPEAN GYNAECOLOGICAL ONCOLOGY TRAINEES: A SURVEY AMONG MEMBERS OF THE EUROPEAN NETWORK OF YOUNG GYNAECOLOGICAL ONCOLOGISTS2016In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 26, p. 598-599Article in journal (Refereed)
  • 1664. Zamora-Ros, R.
    et al.
    Knaze, V.
    Lujan-Barroso, L.
    Kuhnle, G. G. C.
    Mulligan, A. A.
    Touillaud, M.
    Slimani, N.
    Romieu, I.
    Powell, N.
    Tumino, R.
    Peeters, P. H. M.
    de Magistris, M. S.
    Ricceri, F.
    Sonestedt, E.
    Drake, I.
    Hjartaker, A.
    Skie, G.
    Mouw, T.
    Wark, P. A.
    Romaguera, D.
    Bueno-de-Mesquita, H. B.
    Ros, M.
    Molina, E.
    Sieri, S.
    Quiros, J. R.
    Huerta, J. M.
    Tjonneland, A.
    Halkjaer, J.
    Masala, G.
    Teucher, B.
    Kaas, R.
    Travis, R. C.
    Dilis, V.
    Benetou, V.
    Trichopoulou, A.
    Amiano, P.
    Ardanaz, E.
    Boeing, H.
    Foerster, J.
    Clavel-Chapelon, F.
    Fagherazzi, G.
    Perquier, F.
    Johansson, Gerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Cassidy, A.
    Overvad, K.
    Gonzalez, C. A.
    Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort2012In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, no 8, p. 932-941Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36 037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

  • 1665. Zamora-Ros, R
    et al.
    Sacerdote, C
    Ricceri, F
    Weiderpass, E
    Roswall, N
    Buckland, G
    St-Jules, D E
    Overvad, K
    Kyrø, C
    Fagherazzi, G
    Kvaskoff, M
    Severi, G
    Chang-Claude, J
    Kaaks, R
    Nöthlings, U
    Trichopoulou, A
    Naska, A
    Trichopoulos, D
    Palli, D
    Grioni, S
    Mattiello, A
    Tumino, R
    Gram, I T
    Engeset, D
    Huerta, J M
    Molina-Montes, E
    Argüelles, M
    Amiano, P
    Ardanaz, E
    Ericson, U
    Lindkvist, B
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Kiemeney, L A
    Ros, M
    Bueno-de-Mesquita, H B
    Peeters, P H M
    Khaw, K-T
    Wareham, N J
    Knaze, V
    Romieu, I
    Scalbert, A
    Brennan, P
    Wark, P
    Vineis, P
    Riboli, E
    González, C A
    Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2014In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, no 9, p. 1870-1880Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

  • 1666. Zamora-Ros, Raul
    et al.
    Barupal, Dinesh K.
    Rothwell, Joseph A.
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Aleksandrova, Krasimira
    Overvad, Kim
    Kyro, Cecilie
    Tjonneland, Anne
    Affret, Aurelie
    His, Mathilde
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Kuehn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Naska, Androniki
    Kritikou, Maria
    Saieva, Calogero
    Agnoli, Claudia
    de Magistris, Maria Santucci
    Tumino, Rosario
    Fasanelli, Francesca
    Weiderpass, Elisabete
    Skeie, Guri
    Merino, Susana
    Jakszyn, Paula
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Navarro, Carmen
    Ardanaz, Eva
    Sonestedt, Emily
    Ericson, Ulrika
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Bodén, Stina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Perez-Cornago, Aurora
    Wareham, Nicholas J.
    Khaw, Kay-Thee
    Freisling, Heinz
    Cross, Amanda J.
    Riboli, Elio
    Scalbert, Augustin
    Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 8, p. 1836-1844Article in journal (Refereed)
    Abstract [en]

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

  • 1667. Zamora-Ros, Raul
    et al.
    Beraud, Virginie
    Franceschi, Silvia
    Cayssials, Valerie
    Tsilidis, Konstantinos K.
    Boutron-Ruault, Marie-Christine
    Weiderpass, Elisabete
    Overvad, Kim
    Tjonneland, Anne
    Eriksen, Anne K.
    Bonnet, Fabrice
    Affret, Aurelie
    Katzke, Verena
    Kuehn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Valanou, Elisavet
    Karakatsani, Anna
    Masala, Giovanna
    Grioni, Sara
    de Magistris, Maria Santucci
    Tumino, Rosario
    Ricceri, Fulvio
    Skeie, Guri
    Parr, Christine L.
    Merino, Susana
    Salamanca-Fernandez, Elena
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Amiano, Pilar
    Almquist, Martin
    Drake, Isabel
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bueno-de-Mesquita, H. B(as)
    Peeters, Petra H.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Schmidt, Julie A.
    Perez-Cornago, Aurora
    Aune, Dagfinn
    Riboli, Elio
    Slimani, Nadia
    Scalbert, Augustin
    Romieu, Isabelle
    Agudo, Antonio
    Rinaldi, Sabina
    Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 3, p. 449-459Article in journal (Refereed)
    Abstract [en]

    Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p-trend=0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend=0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend=0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend=0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.

  • 1668. Zamora-Ros, Raul
    et al.
    Cayssials, Valerie
    Franceschi, Silvia
    Kyrø, Cecilie
    Weiderpass, Elisabete
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Truong, Thérèse
    Mancini, Francesca Romana
    Katzke, Verena
    Kühn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Karakatsani, Anna
    Martimianaki, Georgia
    Palli, Domenico
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Lasheras, Cristina
    Rodríguez-Barranco, Miguel
    Amiano, Pilar
    Colorado-Yohar, Sandra M.
    Ardanaz, Eva
    Almquist, Martin
    Ericson, Ulrika
    Bueno-de-Mesquita, H. Bas
    Vermeulen, Roel
    Schmidt, Julie A.
    Byrnes, Graham
    Scalbert, Augustin
    Agudo, Antonio
    Rinaldi, Sabina
    Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed)
    Abstract [en]

    Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI >= 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.

  • 1669. Zamora-Ros, Raul
    et al.
    Cayssials, Valerie
    Jenab, Mazda
    Rothwell, Joseph A.
    Fedirko, Veronika
    Aleksandrova, Krasimira
    Tjønneland, Anne
    Kyrø, Cecilie
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Mahamat-Saleh, Yahya
    Kaaks, Rudolf
    Kühn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Valanou, Elissavet
    Vasilopoulou, Effie
    Masala, Giovanna
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Weiderpass, Elisabete
    Lukic, Marko
    Sandanger, Torkjel M.
    Lasheras, Cristina
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Navarro, Carmen
    Ardanaz, Eva
    Sonestedt, Emily
    Ohlsson, Bodil
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Bueno-de-Mesquita, Bas
    Peeters, Petra H.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Bradbury, Kathryn
    Freisling, Heinz
    Romieu, Isabelle
    Cross, Amanda J.
    Vineis, Paolo
    Scalbert, Augustin
    Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2018In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 33, no 11, p. 1063-1075Article in journal (Refereed)
    Abstract [en]

    Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2 = 1.06, 95% CI 0.99–1.14) or in men (HRlog2 = 0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2 = 0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HRlog2 = 1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.

  • 1670. Zamora-Ros, Raul
    et al.
    Fedirko, Veronika
    Trichopoulou, Antonia
    González, Carlos A
    Bamia, Christina
    Trepo, Elisabeth
    Nöthlings, Ute
    Duarte-Salles, Talita
    Serafini, Mauro
    Bredsdorff, Lea
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Fagherazzi, Guy
    Perquier, Florence
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Lukanova, Annekatrin
    Floegel, Anna
    Boeing, Heiner
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Saieva, Calogero
    Agnoli, Claudia
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Bas Bueno-de-Mesquita, H
    Peeters, Petra H M
    Weiderpass, Elisabete
    Engeset, Dagrun
    Skeie, Guri
    Vicente Argüelles, Marcial
    Molina-Montes, Esther
    Dorronsoro, Miren
    José Tormo, María
    Ardanaz, Eva
    Ericson, Ulrika
    Sonestedt, Emily
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Landberg, Rikard
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Crowe, Francesca L
    Riboli, Elio
    Jenab, Mazda
    Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 10, p. 2429-2443Article in journal (Refereed)
    Abstract [en]

    Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case-control subset. During a mean follow-up of 11-years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR = 0.65, 95% CI: 0.40-1.04; ptrend  = 0.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HR = 0.62, 95% CI: 0.39-0.99; ptrend  = 0.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31-0.81; ptrend  = 0.001; TRAP: HR 0.49, 95% CI: 0.31-0.79; ptrend  = 0.002), but statistical significance was lost after exclusion of the first 2 years of follow-up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk.

  • 1671. Zamora-Ros, Raul
    et al.
    Luján-Barroso, Leila
    Bueno-de-Mesquita, H Bas
    Dik, Vincent K
    Boeing, Heiner
    Steffen, Annika
    Tjønneland, Anne
    Olsen, Anja
    Bech, Bodil Hammer
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Fagherazzi, Guy
    Kuhn, Tilman
    Katzke, Verena
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Tumino, Rosario
    Panico, Salvatore
    Vineis, Paolo
    Grioni, Sara
    Palli, Domenico
    Weiderpass, Elisabete
    Skeie, Guri
    Huerta, José María
    Sánchez, María-José
    Argüelles, Marcial
    Amiano, Pilar
    Ardanaz, Eva
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Björn
    Wallström, Peter
    Peeters, Petra H M
    Key, Timothy J
    Khaw, Kay-Thee
    Wareham, Nicholas J
    Freisling, Heinz
    Stepien, Magdalena
    Ferrari, Pietro
    Gunter, Marc J
    Murphy, Neil
    Riboli, Elio
    González, Carlos A
    Tea and coffee consumption and risk of esophageal cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC) study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 6, p. 1470-1479Article in journal (Refereed)
    Abstract [en]

    Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; P-trend=0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; P-trend=0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; P-trend=0.011). However, no statistically significant findings were observed using the continuous variable (per 100mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.

  • 1672. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Biessy, Carine
    Tjonneland, Anne
    Halkjaer, Jytte
    Fournier, Agnes
    Boutron-Ruault, Marie-Christine
    Mesrine, Sylvie
    Tikk, Kaja
    Fortner, Renee T.
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Papatesta, Eleni-Maria
    Masala, Giovanna
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Polidoro, Silvia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Weiderpass, Elisabete
    Lund, Eiliv
    Argueelles, Marcial
    Agudo, Antonio
    Molina-Montes, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Larranaga, Nerea
    Manjer, Jonas
    Almquist, Martin
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tsilidis, Konstantinos K.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Romieu, Isabelle
    Byrnes, Graham
    Gunter, Marc J.
    Riboli, Elio
    Franceschi, Silvia
    Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 5, p. 1218-1227Article in journal (Refereed)
    Abstract [en]

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

  • 1673. Zamora-Ros, Raul
    et al.
    Rinaldi, Sabina
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Rostgaard-Hansen, Agnetha Linn
    Tjonneland, Anne
    Clavel-Chapelon, Francoise
    Mesrine, Sylvie
    Katzke, Verena A.
    Kuehn, Tilman
    Foerster, Jana
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Klinaki, Eleni
    Masala, Giovanna
    Sieri, Sabina
    Ricceri, Fulvio
    Tumino, Rosario
    Mattiello, Amalia
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H. B(as)
    Engeset, Dagrun
    Skeie, Guri
    Argueelles, Marcial
    Agudo, Antonio
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Chamosa, Saioa
    Almquist, Martin
    Tosovic, Ada
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schmidt, Julie A.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Cross, Amanda J.
    Slimani, Nadia
    Byrnes, Graham
    Romieu, Isabelle
    Riboli, Elio
    Franceschi, Silvia
    Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

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

  • 1674.
    Zang, Guangxiang
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Mu, Yabing
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Gao, Linlin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landström, Maréne
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    PKC sigma facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model2019In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 38, no 22, p. 4215-4231Article in journal (Refereed)
    Abstract [en]

    Prostate cancer disseminates primarily into the adjacent lymph nodes, which is related to a poor outcome. Atypical protein kinase C ζ (PKCζ) is highly expressed in aggressive prostate cancer and correlates with Gleason score, clinical stage, and poor prognosis. Here, we report the molecular mechanisms of PKCζ in lymphatic metastasis during prostate cancer progression. Using zinc-finger nuclease technology or PKCζ shRNA lentiviral particles, and orthotopic mouse xenografts, we show that PKCζ-knockout or knockdown from aggressive prostate cancer (PC3 and PC3U) cells, decreasesd tumor growth and lymphatic metastasis in vivo. Intriguingly, PKCζ-knockout or knockdown impaired the activation of AKT, ERK, and NF-κB signaling in prostate cancer cells, thereby impairing the expression of lymphangiogenic factors and macrophage recruitment, resulting in aberrant lymphangiogenesis. Moreover, PKCζ regulated the expression of hyaluronan synthase enzymes, which is important for hyaluronan-mediated lymphatic drainage and tumor dissemination. Thus, PKCζ plays a crucial oncogenic role in the lymphatic metastasis of prostate cancer and is predicted to be a novel therapeutic target for prostate cancer.

  • 1675. Zeleniuch-Jacquotte, A
    et al.
    Shore, R E
    Afanasyeva, Y
    Lukanova, A
    Sieri, S
    Koenig, K L
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Krogh, V
    Liu, M
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Muti, P
    Arslan, A A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, P
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 9, p. 1458-1464Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 1676. Zhang, Mingfeng
    et al.
    Wang, Zhaoming
    Obazee, Ofure
    Jia, Jinping
    Childs, Erica J.
    Hoskins, Jason
    Figlioli, Gisella
    Mocci, Evelina
    Collins, Irene
    Chung, Charles C.
    Hautman, Christopher
    Arslan, Alan A.
    Beane-Freeman, Laura
    Bracci, Paige M.
    Buring, Julie
    Duell, Eric J.
    Gallinger, Steven
    Giles, Graham G.
    Goodman, Gary E.
    Goodman, Phyllis J.
    Kamineni, Aruna
    Kolonel, Laurence N.
    Kulke, Matthew H.
    Malats, Nuria
    Olson, Sara H.
    Sesso, Howard D.
    Visvanathan, Kala
    White, Emily
    Zheng, Wei
    Abnet, Christian C.
    Albanes, Demetrius
    Andreotti, Gabriella
    Brais, Lauren
    Bueno-de-Mesquita, H. Bas
    Basso, Daniela
    Berndt, Sonja I.
    Boutron-Ruault, Marie-Christine
    Bijlsma, Maarten F.
    Brenner, Hermann
    Burdette, Laurie
    Campa, Daniele
    Caporaso, Neil E.
    Capurso, Gabriele
    Cavestro, Giulia Martina
    Cotterchio, Michelle
    Costello, Eithne
    Elena, Joanne
    Boggi, Ugo
    Gaziano, J. Michael
    Gazouli, Maria
    Giovannucci, Edward L.
    Goggins, Michael
    Gross, Myron
    Haiman, Christopher A.
    Hassan, Manal
    Helzlsouer, Kathy J.
    Hu, Nan
    Hunter, David J.
    Iskierka-Jazdzewska, Elzbieta
    Jenab, Mazda
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay-Tee
    Klein, Eric A.
    Kogevinas, Manolis
    Krogh, Vittorio
    Kupcinskas, Juozas
    Kurtz, Robert C.
    Landi, Maria T.
    Landi, Stefano
    Le Marchand, Loic
    Mambrini, Andrea
    Mannisto, Satu
    Milne, Roger L.
    Neale, Rachel E.
    Oberg, Ann L.
    Panico, Salvatore
    Patel, Alpa V.
    Peeters, Petra H. M.
    Peters, Ulrike
    Pezzilli, Raffaele
    Porta, Miquel
    Purdue, Mark
    Ramon Quiros, J.
    Riboli, Elio
    Rothman, Nathaniel
    Scarpa, Aldo
    Scelo, Ghislaine
    Shu, Xiao-Ou
    Silverman, Debra T.
    Soucek, Pavel
    Strobel, Oliver
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Malecka-Panas, Ewa
    Taylor, Philip R.
    Tavano, Francesca
    Travis, Ruth C.
    Thornquist, Mark
    Tjonneland, Anne
    Tobias, Geoffrey S.
    Trichopoulos, Dimitrios
    Vashist, Yogesh
    Vodicka, Pavel
    Wactawski-Wende, Jean
    Wentzensen, Nicolas
    Yu, Herbert
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Kooperberg, Charles
    Risch, Harvey A.
    Jacobs, Eric J.
    Li, Donghui
    Fuchs, Charles
    Hoover, Robert
    Hartge, Patricia
    Chanock, Stephen J.
    Petersen, Gloria M.
    Stolzenberg-Solomon, Rachael S.
    Wolpin, Brian M.
    Kraft, Peter
    Klein, Alison P.
    Canzian, Federico
    Amundadottir, Laufey T.
    Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.212016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 41, p. 66328-66343Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

  • 1677. Zhang, Xiangwei
    et al.
    Wang, Yang
    Li, Cheng
    Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jiang, Yuanzhu
    Ma, Guoyuan
    Wang, Guanghui
    Dong, Wei
    Sang, Shaowei
    Du, Jiajun
    The prognostic value of tumor length to resectable esophageal squamous cell carcinoma: a retrospective study2017In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 5, article id e2943Article in journal (Refereed)
    Abstract [en]

    Background: The current TNM classification system does not consider tumor length for patients with esophageal carcinoma (EC). This study explored the effect of tumor length, in addition to tumor depth and lymph node involvement, on survival in patients with esophageal squamous cell carcinoma (ESCC).

    Methods: A total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study. Pathological details were collected, which included tumor type, TNM stage, differentiation. Other collected information were: the types of esophageal resection, ABO blood group, family history and demographic and lifestyle factors. A time-dependent receiver operating characteristic (ROC) curve and a regression tree for survival were used to identify the cut-off point of tumor length, which was 3 cm. Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC.

    Results & Discussion: The 1-, 3-, 5-year overall survival rates were found to be 82.5%, 55.6%, and 35.1%, respectively. Patients who had larger tumor length (>3 cm) had a higher risk for death than the rest patients. From the univariate Cox proportional hazards regression model, the overall survival rate was significantly influenced by the depth of the tumor and lymph node involvement (either as dummy or continuous variables), Sex, and tumor length. Using these four variables in the multivariate Cox proportional hazard regression model, we found that the overall survival was significantly influenced by all variables except Sex. Therefore, in addition to the depth of the tumor and lymph node involvement (as either dummy or continuous variables), the tumor length is also an independent prognostic factor for ESCC. The overall survival rate was higher in a group with smaller tumor length (≤3 cm) than those patients with larger tumor length (>3 cm), no matter what the tumor stage was.

    Conclusion: The tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy. The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.

  • 1678. Zhang, Xiangwei
    et al.
    Wang, Yang
    Qu, Pengfei
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Zhao, Linping
    Zhang, Lin
    Sang, Shaowei
    The Prognostic Value of Tumor Length for Cause-Specific Mortality in Resectable Esophageal Cancer.2018In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 106, no 4, p. 1038-1046Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The current esophageal cancer AJCC-TNM staging system may not capture the full prognostic implications of the primary tumor. A study is needed to explore the prognostic value of tumor size on esophageal cancer-specific mortality.

    METHODS: Patients who underwent surgical resection for non-metastatic esophageal cancer were selected from the Surveillance, Epidemiology and End Results Program database (United States, 1988 - 2014). Using statistics methods - maximally selected rank and two hazard models (Cox model and Fine-Gray model) - the optimum cutoff point for tumor length in each T classification was estimated and the prognostic value of tumor size on esophageal cancer-specific mortality was analyzed.

    RESULTS: 4,447 patients were identified. The median tumor size was significantly correlated with T classification, with the correlation coefficient of 0.43 (p < 0.001). Patients in the T1-T3 classifications who had larger tumor size showed a larger probability of cancer-specific mortality. The multivariate Cox model showed that tumor size was significantly associated with an increase in cancer-specific mortality in T1 (2.15, 95% CI [1.72, 2.69]) and T2 (1.31, 95% CI [1.06, 1.62]), but marginally significantly in T3 (1.12, 95% CI [1.00, 1.27]) and insignificantly in T4 classification (p > 0.1). Similar results were found using the multivariate Fine-Gray model.

    CONCLUSIONS: We have found that combining T classification with tumor size can increase the precision in identifying the high-risk groups in T1-T2 classification. Based on esophageal cancer-specific mortality our study is the first to explore the prognostic cutoff point of tumor size by T classification.

  • 1679. Zheng, Jiaojiao
    et al.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Santoni, Giola
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Xie, Shao-Hua
    Lagergren, Jesper
    Prediabetes and diabetes in relation to risk of gastric adenocarcinoma2019In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, no 12, p. 1147-1152Article in journal (Refereed)
    Abstract [en]

    Background: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear.

    Methods: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level.

    Results: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79–1.44), diabetes (HR 0.77, 95% CI 0.46–1.29) or any of these exposures (HR 0.96, 95% CI 0.73–1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma.

    Conclusions: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

  • 1680. Zhu, Ying
    et al.
    Wei, Yongyue
    Zhang, Ruyang
    Dong, Xuesi
    Shen, Sipeng
    Zhao, Yang
    Bai, Jianling
    Albanes, Demetrius
    Caporaso, Neil E.
    Landi, Maria Teresa
    Zhu, Bin
    Chanock, Stephen J.
    Gu, Fangyi
    Lam, Stephen
    Tsao, Ming-Sound
    Shepherd, Frances A.
    Tardon, Adonina
    Fernandez-Somoano, Ana
    Fernandez-Tardon, Guillermo
    Chen, Chu
    Barnett, Matthew J.
    Doherty, Jennifer
    Bojesen, Stig E.
    Johansson, Mattias
    Brennan, Paul
    Mckay, James D.
    Carreras-Torres, Robert
    Muley, Thomas
    Risch, Angela
    Wichmann, Heunz-Erich
    Bickeboeller, Heike
    Rosenberger, Albert
    Rennert, Gad
    Saliba, Walid
    Arnold, Susanne M.
    Field, John K.
    Davies, Michael P. A.
    Marcus, Michael W.
    Wu, Xifeng
    Ye, Yuanqing
    Le Marchand, Loic
    Wilkens, Lynne R.
    Melander, Olle
    Manjer, Jonas
    Brunnstrom, Hans
    Hung, Rayjean J.
    Liu, Geoffrey
    Brhane, Yonathan
    Kachuri, Linda
    Andrew, Angeline S.
    Duell, Eric J.
    Kiemeney, Lambertus A.
    van der Heijden, Erik H. F. M.
    Haugen, Aage
    Zienolddiny, Shanbeh
    Skaug, Vidar
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Woll, Penella J.
    Cox, Angela
    Taylor, Fiona
    Teare, Dawn M.
    Lazarus, Philip
    Schabath, Matthew B.
    Aldrich, Melinda C.
    Houlston, Richard S.
    McLaughlin, John
    Stevens, Victoria L.
    Shen, Hongbing
    Hu, Zhibin
    Dai, Juncheng
    Amos, Christopher I.
    Han, Younghun
    Zhu, Dakai
    Goodman, Gary E.
    Chen, Feng
    Christiani, David C.
    Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis2019In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 5, p. 935-942Article in journal (Refereed)
    Abstract [en]

    Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall nonsmall cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

  • 1681. Zirakzadeh, A. Ali
    et al.
    Marits, Per
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winqvist, Ola
    Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies2013In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 190, no 11, p. 5847-5855Article in journal (Refereed)
    Abstract [en]

    B lymphocytes contribute to immune surveillance, by tumor-specific Abs and Ag presentation to T lymphocytes, but are insufficiently studied in humans. In this article, we report a flow cytometric investigation of B lymphocyte subpopulations in blood, lymph nodes (LNs), and malignant tissues from 20 patients operated on because of advanced solid tumors. The CD19(+) compartment in peripheral blood was essentially unaltered in patients, as compared with healthy control subjects. In metastatic LNs, signs of B lymphocyte activation were observed, as evidenced by increased proportions of plasmablasts and CD86-expressing cells. In tumor-infiltrating B lymphocytes (TIL-B), both switched memory cells and plasmablasts were expanded, as compared with nonmalignant epithelium. Moreover, pronounced skewing of Ig lambda/Ig kappa ratio was evident among TIL-Bs. By spectratype analysis on IgH, we confirmed a monoclonal expansion of the Vh7 family in TIL-B, also present in a tumor-associated LN. Sequencing the clonally expanded Vh7 revealed signs of somatic hypermutation. In conclusion, B lymphocytes in cancer patients exhibit signs of activation in tumor-associated tissues, likely induced by recognition of tumor Ags. Increased numbers of switched memory cells and plasmablasts in combination with clonal expansion and signs of somatic hypermutation suggest a CD4(+) T lymphocyte-dependent antitumoral response, which may be exploited for immunotherapy.

  • 1682. Zolochevska, Olga
    et al.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Comeaux, Brennen
    Emrick, Todd
    Figueiredo, Marxa L
    Novel antitumor strategies using cytokine PEDF for prostate cancer therapy2012In: Current Angiogenesis, ISSN 2211-5528 (print), 2211-5536 (online), Vol. 1, no 4, p. 277-298Article in journal (Refereed)
    Abstract [en]

    Prostate cancer is the most common solid tumor affecting men in the United States and Western Europe. Currently, therapeutic options remain limited and novel therapies are needed that can provide low toxicity and high therapeutic index. One promising new agent is a potent inhibitor of angiogenesis with anti-metastatic activities, the pigment epithelium- derived factor (PEDF). Some additional functions of PEDF that augment its promise as a new therapeutic include its pro-apoptosis (tumor cells and tumor-associated endothelial cells) and potential pro-immunogenic (cytotoxic macrophages) activities. We will discuss findings by several groups using PEDF as an efficient therapeutic following many delivery strategies including gene, protein, peptide, or cell-based therapy. PEDF also has potential to serve as a proteomics biomarker for prostate cancer progression, as downregulated levels could help predict metastatic potential of tumors. We will provide an overview of the potential and promise for achieving translation of PEDF therapeutics for the treatment of advanced prostate cancer.

  • 1683. Zovko, Ana
    et al.
    Yektaei-Karin, Elham
    Salamon, Daniel
    Nilsson, Anders
    Wallvik, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Stenke, Leif
    Montelukast, a cysteinyl leukotriene receptor antagonist, inhibits the growth of chronic myeloid leukemia cells through apoptosis2018In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 40, no 2, p. 902-908Article in journal (Refereed)
    Abstract [en]

    The clinical outcome for patients with chronic myeloid leukemia (CML) has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs). However, their curative potential appears limited, probably as a consequence of TKI-resistant leukemic stem cells (LSCs) that persist as a result of aberrant pathways independent of the well-established oncoprotein Bcr-Abl. One such pathway involves signaling through leukotrienes (LTs), bioactive compounds that have been suggested to play a role in several other malignancies. Cysteinyl LT1 receptor (CysLT1R) has been reported to be overexpressed in a number of solid cancers, and blocking of this receptor with the antagonist montelukast (treatment approved for bronchial asthma) has resulted in the killing of cancer cells. We recently demonstrated that montelukast, alone or in combination with imatinib, can effectively reduce the growth of CML cells, while normal bone marrow cells were left unaffected. Herein, we further investigated the importance of CysLT1R for the survival of CML cells and the mechanisms by which montelukast induces cell death. Knockdown of the CysLT1R of K562 cells with siRNA reduced their growth by 25%. Montelukast had no effect on these cells, while it killed more than 50% of CysLT1R-expressing cells. Growth inhibition exerted by imatinib was unaffected by CysLT1R status. Montelukast-induced killing of K562/JURL-MK1 CML cells was paralleled by Bax overexpression, cytochrome c release, PARP-1 cleavage, and caspase-3 activation, an event further increased in a setting where montelukast was added to imatinib. Wnt/-catenin signaling was activated by CysLT1R and we observed that montelukast could induce proteins in this pathway, a finding of relevance for LSC survival. Thus, montelukast, employed at in vivo-like concentrations, induces the killing of CML cells through apoptotic pathways and may provide an additional, novel therapeutic possibility in CML.

  • 1684. Zuo, H.
    et al.
    Ueland, P. M.
    Midttun, O.
    Tell, G. S.
    Fanidi, A.
    Zheng, W.
    Shu, X.
    Xiang, Y.
    Wu, J.
    Prentice, R.
    Pettinger, M.
    Thomson, C. A.
    Giles, G. G.
    Hodge, A.
    Cai, Q.
    Blot, W. J.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stevens, V. L.
    McCullough, M. L.
    Weinstein, S. J.
    Albanes, D.
    Ziegler, R. G.
    Freedman, N. D.
    Caporaso, N. E.
    Langhammer, A.
    Hveem, K.
    Naess, M.
    Buring, J. E.
    Lee, I.
    Gaziano, J. M.
    Severi, G.
    Zhang, X.
    Stampfer, M. J.
    Han, J.
    Zeleniuch-Jacquotte, A.
    Marchand, L. L.
    Yuan, J.
    Wang, R.
    Koh, W.
    Gao, Y.
    Ericson, U.
    Visvanathan, K.
    Jones, M. R.
    Relton, C.
    Brennan, P.
    Ulvik, A.
    Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3)2019In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 30, no 3, p. 478-485Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 1685. Zuo, Hui
    et al.
    Ueland, Per Magne
    Midttun, Øivind
    Vollset, Stein E
    Tell, Grethe S
    Theofylaktopoulou, Despoina
    Travis, Ruth C
    Boutron-Ruault, Marie-Christine
    Fournier, Agnes
    Severi, Gianluca
    Kvaskoff, Marina
    Boeing, Heiner
    Bergmann, Manuela
    Fortner, Renée Turzanski
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Kotanidou, Anastasia
    Lagiou, Pagona
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Bueno-de-Mesquita, H B As
    Peeters, Petra H
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Agudo, Antonio
    Quirós Garcia, Jose Ramón
    Larrañaga, Nerea
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Chuang, Shu-Chun
    Gallo, Valentina
    Brennan, Paul
    Johansson, Mattias
    Ulvik, Arve
    Results from the European Prospective Investigation into Cancer and Nutrition Link Vitamin B6 Catabolism and Lung Cancer Risk2018In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 1, p. 302-308Article in journal (Refereed)
    Abstract [en]

    Circulating pyridoxal-5′-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose–response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27–1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.

  • 1686.
    Ångstrom-Brännström, Charlotte
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Engvall, G.
    Mullaney, T.
    Nilsson, K.
    Wickart-Johansson, G.
    Svärd, A. M.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Facilitating Radiotherapy for Children: Technique, Design and Professional Care in Synergy, a Multicenter Intervention Study2016In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, p. S213-S213Article in journal (Other academic)
  • 1687.
    Ångström-Brännström, Charlotte
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Engvall, Gunn
    Mullaney, Tara
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Nilsson, Kristina
    Wickart-Johansson, Gun
    Svärd, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindh, Viveca
    Umeå University, Faculty of Medicine, Department of Nursing.
    Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0141086Article in journal (Refereed)
    Abstract [en]

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multi-center study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.

  • 1688.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Prognostic factors in colorectal cancer: aspects of tumour dissemination2002Doctoral thesis, comprehensive summary (Other academic)
  • 1689.
    Öberg, Åke
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindmark, Gudrun
    Department of Surgery, Helsingborgs Lasarett, Lund University, Helsingborg, Sweden.
    Israelsson, Anne CE
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Sten G
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise KC
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 111, no 1, p. 101-110Article in journal (Refereed)
    Abstract [en]

    The purpose of our study was to develop specific, sensitive, objective assays for early detection of disseminated tumour cells in patients with colorectal cancer (CRC). Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as markers because they are selectively expressed in epithelial cells with maintained expression in CRC. Real-time quantitative RT-PCR assays with RNA copy standards were constructed. Regional lymph nodes were collected from patients with CRC (n = 51) and benign intestinal disease (n = 10). Results were compared to routine histopathology and anti-CEA immunohistochemistry. Lymph node levels of CEA and CK20 mRNA correlated strongly (p < 0.0001, r = 0.8). Lymph nodes from non-CRC patients had <0.01 CEA and <0.001 CK20 mRNA copies/18S rRNA unit. Lymph nodes from 3/6 Dukes' A, 17/26 Dukes' B, 10/10 Dukes' C and 7/9 Dukes' D patients had CEA mRNA levels above cut-off. Corresponding figures for CK20 mRNA were 3/6, 10/26, 9/10 and 5/9, respectively. CEA mRNA levels varied from 0.001 to 100 copies/18S rRNA unit in Dukes' A and B, and 50% of the Dukes' B patients had CEA mRNA levels within the range of Dukes' C patients. Three Dukes' B patients have died from CRC or developed distant metastases. All 3 had high CEA and CK20 mRNA levels. Determination of mRNA was superior to immunohistochemistry in showing CEA expression in lymph nodes. The present qRT-PCR assay for CEA mRNA seems to be a superior tool to identify individuals with disseminated tumour cells. Future extended studies will establish the clinically most relevant cut-off level.

  • 1690.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Cold Spring Harbor Laboratory and Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724.
    Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer2017In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 3, p. 579-596Article in journal (Refereed)
    Abstract [en]

    Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of a-smooth muscle actin (alpha SMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated aSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.

  • 1691.
    Öhlund, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, article id 154Article in journal (Refereed)
    Abstract [en]

    Background: Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized.

    Methods: The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule.

    Results: We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis.

    Conclusion: We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.

  • 1692.
    Öster, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hedestig, Oliver
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Mona
    Umeå University, Faculty of Medicine, Department of Nursing.
    Klingstedt, Nina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sharing experiences in a support group: men's talk during the radiotherapy period for prostate cancer2013In: Palliative & Supportive Care, ISSN 1478-9515, E-ISSN 1478-9523, Vol. 11, no 4, p. 331-339Article in journal (Refereed)
    Abstract [en]

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

31323334 1651 - 1692 of 1692
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