50 results on '"Ehrnström, R."'
Search Results
2. Artificial Intelligence for automated Gleason Grading in prostate cancer biopsies
- Author
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Marginean, F-E., primary, Krzyzanowska, A., additional, Arvidsson, I., additional, Simoulis, A., additional, Sjöblom, E., additional, Lundström, C., additional, Overgaard, N.C., additional, Ehrnström, R., additional, Åström, K., additional, Heyden, A., additional, and Bjartell, A., additional
- Published
- 2019
- Full Text
- View/download PDF
3. Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
- Author
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Buckland, G, Ros, M, Roswall, N, Bueno-De-Mesquita, H, Travier, N, Tjonneland, A, Kiemeney, L, Sacerdote, C, Tumino, R, Ljungberg, B, Gram, I, Weiderpass, E, Skeie, G, Malm, J, Ehrnström, R, Chang-Claude, J, Mattiello, A, Agnoli, C, Peeters, P, Boutron-Ruault, M, Fagherazzi, G, Clavel-Chapelon, F, Nilsson, L, Amiano, P, and Trichopoulou, A
- Abstract
There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. © 2013 UICC.
- Published
- 2016
4. 544 - Artificial Intelligence for automated Gleason Grading in prostate cancer biopsies
- Author
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Marginean, F-E., Krzyzanowska, A., Arvidsson, I., Simoulis, A., Sjöblom, E., Lundström, C., Overgaard, N.C., Ehrnström, R., Åström, K., Heyden, A., and Bjartell, A.
- Published
- 2019
- Full Text
- View/download PDF
5. Aberrant DNA methylation of cancer-associatedgenes in gastric cancer in the European Prospective Investigation into Cancer andNutrition (EPIC-EURGAST)
- Author
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Balassiano K, Lima S, Jenab M, Overvad K, Tjonneland A, Boutron Ruault MC, Clavel Chapelon F, Canzian F, Kaaks R, Boeing H, Meidtner K, Trichopoulou A, Laglou P, Vineis P, Palli D, Grioni S, Tumino R, Lund E, Bueno de Mesquita HB, Numans ME, Peeters PH, Ramon Quirós J, Sánchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Hallmans G, Stenling R, Ehrnström R, Regner S, Allen NE, Travis RC, Khaw KT, Offerhaus GJ, Sala N, Riboli E, Hainaut P, Scoazec JY, Sylla BS, Gonzalez CA, Herceg Z., PANICO, SALVATORE, Balassiano, K, Lima, S, Jenab, M, Overvad, K, Tjonneland, A, Boutron Ruault, Mc, Clavel Chapelon, F, Canzian, F, Kaaks, R, Boeing, H, Meidtner, K, Trichopoulou, A, Laglou, P, Vineis, P, Panico, Salvatore, Palli, D, Grioni, S, Tumino, R, Lund, E, Bueno de Mesquita, Hb, Numans, Me, Peeters, Ph, Ramon Quirós, J, Sánchez, Mj, Navarro, C, Ardanaz, E, Dorronsoro, M, Hallmans, G, Stenling, R, Ehrnström, R, Regner, S, Allen, Ne, Travis, Rc, Khaw, Kt, Offerhaus, Gj, Sala, N, Riboli, E, Hainaut, P, Scoazec, Jy, Sylla, B, Gonzalez, Ca, and Herceg, Z.
- Published
- 2011
6. Variety in vegetable and fruit consumption and risk of bladder cancer in theEuropean Prospective Investigation into Cancer and Nutrition
- Author
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Büchner FL, Bueno de Mesquita HB, Ros MM, Kampman E, Egevad L, Overvad K, Tjønneland A, Roswall N, Clavel Chapelon F, Boutron Ruault MC, Touillaud M, Kaaks R, Chang Claude J, Boeing H, Weikert S, Trichopoulou A, Naska A, Benetou V, Palli D, Sieri S, Vineis P, Tumino R, van Duijnhoven FJ, Peeters PH, van Gils CH, Lund E, Gram IT, Sánchez MJ, Jakszyn P, Larrañaga N, Ardanaz E, Navarro C, Rodríguez L, Manjer J, Ehrnström R, Hallmans G, Ljungberg B, Key TJ, Allen NE, Khaw KT, Wareham N, Slimani N, Jenab M, Boffetta P, Kiemeney LA, Riboli E., PANICO, SALVATORE, Büchner, Fl, Bueno de Mesquita, Hb, Ros, Mm, Kampman, E, Egevad, L, Overvad, K, Tjønneland, A, Roswall, N, Clavel Chapelon, F, Boutron Ruault, Mc, Touillaud, M, Kaaks, R, Chang Claude, J, Boeing, H, Weikert, S, Trichopoulou, A, Naska, A, Benetou, V, Palli, D, Sieri, S, Vineis, P, Tumino, R, Panico, Salvatore, van Duijnhoven, Fj, Peeters, Ph, van Gils, Ch, Lund, E, Gram, It, Sánchez, Mj, Jakszyn, P, Larrañaga, N, Ardanaz, E, Navarro, C, Rodríguez, L, Manjer, J, Ehrnström, R, Hallmans, G, Ljungberg, B, Key, Tj, Allen, Ne, Khaw, Kt, Wareham, N, Slimani, N, Jenab, M, Boffetta, P, Kiemeney, La, and Riboli, E.
- Published
- 2011
7. Fruit and vegetable intake and the risk of gastric adenocarcinoma: A reanalysis of the european prospective investigation into cancer and nutrition (EPIC-EURGAST) study after a longer follow-up
- Author
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Gonzalez, C.A. Lujan-Barroso, L. Bueno-De-Mesquita, H.B. Jenab, M. Duell, E.J. Agudo, A. Tjønneland, A. Boutron-Ruault, M.C. Clavel-Chapelon, F. Touillaud, M. Teucher, B. Kaaks, R. Boeing, H. Steffen, A. Trichopoulou, A. Roukos, D. Karapetyan, T. Palli, D. Tagliabue, G. Mattiello, A. Tumino, R. Ricceri, F. Siersema, P.D. Numans, M.E. Peeters, P.P.H. Parr, C.L. Skeie, G. Lund, E. Quirõs, J.R. Sánchez-Cantalejo, E. Navarro, C. Barricarte, A. Dorronsoro, M. Ehrnström, R. Regner, S. Khaw, K.-T. Wareham, N. Key, T.J. Crowe, F.L. Blaker, H. Romieu, I. Riboli, E.
- Subjects
food and beverages - Abstract
In a previous European prospective investigation into cancer and nutrition (EPIC) analysis, we found an inverse association between total intake of vegetables, onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of fruit and vegetables (F&V), based on a longer follow-up and twice the number of GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11 years of follow-up. Information on diet and lifestyle was collected at baseline. A calibration study in a subsample was used to correct for dietary measurement errors. When comparing the highest vs. lowest quintile of intake, we found an inverse association between total intake of V&F and GC risk [hazard ratio (HR) 0.77; 95% confidence interval (CI) 0.57-1.04; p for trend 0.02], between fresh fruit and risk of the diffuse type (HR 0.59; 95% CI 0.36-0.97; p for trend 0.03) and an inverse association between citrus fruit and risk of cardia cancer (HR 0.61; 95% CI 0.38-1.00, p for trend 0.01). Although calibration revealed somewhat stronger inverse associations, none of the risks reached statistical significance. There was no association between total or specific vegetables intake and GC risk. The inverse association between fresh fruit and citrus fruits and risk of GC seems to be restricted to smokers and the Northern European countries. Fresh fruit and citrus fruit consumption may protect against diffuse and cardia GC, respectively. Copyright © 2012 UICC.
- Published
- 2012
8. Variety in vegetable and fruit consumption and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition
- Author
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Büchner, F.L. Bueno-De-Mesquita, H.B. Ros, M.M. Kampman, E. Egevad, L. Overvad, K. Tjãnneland, A. Roswall, N. Clavel-Chapelon, F. Boutron-Ruault, M.-C. Touillaud, M. Kaaks, R. Chang-Claude, J. Boeing, H. Weikert, S. Trichopoulou, A. Naska, A. Benetou, V. Palli, D. Sieri, S. Vineis, P. Tumino, R. Panico, S. Van Duijnhoven, F.J.B. Peeters, P.H.M. Van Gils, C.H. Lund, E. Gram, I.T. Sánchez, M.-J. Jakszyn, P. Larrañaga, N. Ardanaz, E. Navarro, C. Rodríguez, L. Manjer, J. Ehrnström, R. Hallmans, G. Ljungberg, B. Key, T.J. Allen, N.E. Khaw, K.-T. Wareham, N. Slimani, N. Jenab, M. Boffetta, P. Kiemeney, L.A.L.M. Riboli, E.
- Abstract
Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk. © 2010 UICC.
- Published
- 2011
9. Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- Author
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Jakszyn, P. González, C.A. Luján-Barroso, L. Ros, M.M. Bueno-de-Mesquita, H.B. Roswall, N. Tjønneland, A.M. Büchner, F.L. Egevad, L. Overvad, K. Raaschou-Nielsen, O. Clavel-Chapelon, F. Boutron-Ruault, M.-C. Touillaud, M.S. Chang-Claude, J. Allen, N.E. Kiemeney, L.A. Key, T.J. Kaaks, R. Boeing, H. Weikert, S. Trichopoulou, A. Oikonomou, E. Zylis, D. Palli, D. Berrino, F. Vineis, P. Tumino, R. Mattiello, A. Peeters, P.H.M. Parr, C.L. Gram, I.T. Skeie, G. Sánchez, M.-J. Larrañaga, N. Ardanaz, E. Navarro, C. Rodríguez, L. Ulmert, D. Ehrnström, R. Hallmans, G. Ljungberg, B. Roddam, A.W. Bingham, S.A. Khaw, K.-T. Slimani, N. Boffetta, P.A. Jenab, M. Mouw, T. Michaud, D.S. Riboli, E.
- Abstract
Background: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI. Results: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99-1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92-1.30 and HR: 0.98; 95% CI: 0.92-1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99-1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk). Conclusions: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk. ©2011 AACR.
- Published
- 2011
10. Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
- Author
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Buckland, G, Ros, M M, Roswall, N, Bueno-de-Mesquita, H B, Travier, N, Tjonneland, A, Kiemeney, L A, Sacerdote, C, Tumino, R, Ljungberg, Börje, Gram, I T, Weiderpass, E, Skeie, G, Malm, J, Ehrnström, R, Chang-Claude, J, Mattiello, A, Agnoli, C, Peeters, P H, Boutron-Ruault, M C, Fagherazzi, G, Clavel-Chapelon, F, Nilsson, Lena Maria, Amiano, P, Trichopoulou, A, Oikonomou, E, Tsiotas, K, Sánchez, M J, Overvad, K, Quirós, J R, Chirlaque, M D, Barricarte, A, Key, T J, Allen, N E, Khaw, K T, Wareham, N, Riboli, E, Kaaks, R, Boeing, H, Palli, D, Romieu, I, Romaguera, D, Gonzalez, C A, Buckland, G, Ros, M M, Roswall, N, Bueno-de-Mesquita, H B, Travier, N, Tjonneland, A, Kiemeney, L A, Sacerdote, C, Tumino, R, Ljungberg, Börje, Gram, I T, Weiderpass, E, Skeie, G, Malm, J, Ehrnström, R, Chang-Claude, J, Mattiello, A, Agnoli, C, Peeters, P H, Boutron-Ruault, M C, Fagherazzi, G, Clavel-Chapelon, F, Nilsson, Lena Maria, Amiano, P, Trichopoulou, A, Oikonomou, E, Tsiotas, K, Sánchez, M J, Overvad, K, Quirós, J R, Chirlaque, M D, Barricarte, A, Key, T J, Allen, N E, Khaw, K T, Wareham, N, Riboli, E, Kaaks, R, Boeing, H, Palli, D, Romieu, I, Romaguera, D, and Gonzalez, C A
- Abstract
There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.
- Published
- 2014
- Full Text
- View/download PDF
11. Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
- Author
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Buckland, G., primary, Ros, M.M., additional, Roswall, N., additional, Bueno-de-Mesquita, H.B., additional, Travier, N., additional, Tjonneland, A., additional, Kiemeney, L.A., additional, Sacerdote, C., additional, Tumino, R., additional, Ljungberg, B., additional, Gram, I.T., additional, Weiderpass, E., additional, Skeie, G., additional, Malm, J., additional, Ehrnström, R., additional, Chang-Claude, J., additional, Mattiello, A., additional, Agnoli, C., additional, Peeters, P.H., additional, Boutron-Ruault, M.C., additional, Fagherazzi, G., additional, Clavel-Chapelon, F., additional, Nilsson, L.M., additional, Amiano, P., additional, Trichopoulou, A., additional, Oikonomou, E., additional, Tsiotas, K., additional, Sánchez, M.J., additional, Overvad, K., additional, Quirós, J.R., additional, Chirlaque, M.D, additional, Barricarte, A., additional, Key, T.J., additional, Allen, N.E., additional, Khaw, K.T., additional, Wareham, N., additional, Riboli, E., additional, Kaaks, R., additional, Boeing, H., additional, Palli, D., additional, Romieu, I., additional, Romaguera, D., additional, and Gonzalez, C.A., additional
- Published
- 2013
- Full Text
- View/download PDF
12. 1050 NATION-WIDE POPULATION-BASED STUDY ON 15-YEAR MORTALITY IN PROSTATE CANCER ACCORDING TO RISK CATEGORIES IN THE NATIONAL PROSTATE CANCER REGISTER (NPCR) OF SWEDEN
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Stattin, P., primary, Sandin, F., additional, Ahlgren, G., additional, Bratt, O., additional, Damber, J.E., additional, Hugosson, J., additional, Pettersson, B., additional, Robinson, D., additional, Törnblom, M., additional, Karlsson, S., additional, Andrén, O., additional, Bill-Axelson, A., additional, Widmark, A., additional, Egevad, L., additional, Ehrnström, R., additional, Adolfsson, J., additional, Lambe, M., additional, and Johansson, J.E., additional
- Published
- 2011
- Full Text
- View/download PDF
13. THE IDENTIFICATION OF A NOVEL STROMAL STEM/PROGENITOR CELL PHENOTYPE IN THE HUMAN ADULT PROSTATE
- Author
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Ceder, J., primary, Jansson, L., additional, Ehrnström, R., additional, Rönnstrand, L., additional, and Abrahamsson, P.A., additional
- Published
- 2008
- Full Text
- View/download PDF
14. 511 CD117, A NOVEL CANDIDATE MARKER FOR HUMAN PROSTATE EPITHELIAL STEM CELLS
- Author
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Hansson, J., primary, Ivarsson, L., additional, Ehrnström, R., additional, Helczynski, L., additional, and Abrahamsson, P.A., additional
- Published
- 2007
- Full Text
- View/download PDF
15. EXPRESSION OF PROGENITOR CELL MARKERS IN PROLIFERATING BASAL CELLS OF HUMAN PROSTATIC EXPLANT CULTURES
- Author
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Hansson, J., primary, Ivarsson, L., additional, Ehrnström, R., additional, Helczynski, L., additional, Bjartell, A., additional, and Abrahamsson, P.A., additional
- Published
- 2006
- Full Text
- View/download PDF
16. 92 THE IDENTIFICATION OF A NOVEL STROMAL STEM/PROGENITOR CELL PHENOTYPE IN THE HUMAN ADULT PROSTATE
- Author
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Ceder, J., Jansson, L., Ehrnström, R., Rönnstrand, L., and Abrahamsson, P.A.
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- 2008
- Full Text
- View/download PDF
17. Variety in vegetable and fruit consumption and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition
- Author
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Marina Touillaud, Rudolf Kaaks, Antonia Trichopoulou, Inger T. Gram, Roy Ehrnström, Nina Roswall, Paula Jakszyn, Ellen Kampman, Kay-Tee Khaw, Elio Riboli, H. Bas Bueno-de-Mesquita, Nerea Larrañaga, Marie-Christine Boutron-Ruault, Eva Ardanaz, Carmen Navarro, Kim Overvad, Eiliv Lund, Naomi E. Allen, Carla H. van Gils, Timothy J. Key, Laudina Rodríguez, Martine M. Ros, Paolo Vineis, María José Sánchez, Vicky Benetou, Lambertus A. Kiemeney, Sabina Sieri, Françoise Clavel-Chapelon, A. Naska, Frederike L. Büchner, Rosario Tumino, Lars Egevad, Nicholas J. Wareham, Mazda Jenab, Heiner Boeing, Jonas Manjer, Nadia Slimani, Anne Tjønneland, Petra H.M. Peeters, Fränzel J.B. Van Duijnhoven, Börje Ljungberg, Paolo Boffetta, Steffen Weikert, Domenico Palli, Jenny Chang-Claude, Salvatore Panico, Göran Hallmans, Büchner, F.L., Bueno-De-Mesquita, H.B., Ros, M.M., Kampman, E., Egevad, L., Overvad, K., Tjãnneland, A., Roswall, N., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Touillaud, M., Kaaks, R., Chang-Claude, J., Boeing, H., Weikert, S., Trichopoulou, A., Naska, A., Benetou, V., Palli, D., Sieri, S., Vineis, P., Tumino, R., Panico, S., Van Duijnhoven, F.J.B., Peeters, P.H.M., Van Gils, C.H., Lund, E., Gram, I.T., Sánchez, M.-J., Jakszyn, P., Larrañaga, N., Ardanaz, E., Navarro, C., Rodríguez, L., Manjer, J., Ehrnström, R., Hallmans, G., Ljungberg, B., Key, T.J., Allen, N.E., Khaw, K.-T., Wareham, N., Slimani, N., Jenab, M., Boffetta, P., Kiemeney, L.A.L.M., and Riboli, E.
- Subjects
Male ,Cancer Research ,validity ,Nutrition and Disease ,Colorectal cancer ,pharyngeal cancer ,Food group ,0302 clinical medicine ,Risk Factors ,diet diversity ,Voeding en Ziekte ,Vegetables ,vegetable ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,bladder ,risk ,2. Zero hunger ,Hazard ratio ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Europe ,Oncology ,030220 oncology & carcinogenesis ,food groups ,Female ,colon-cancer ,medicine.medical_specialty ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Translational research [ONCOL 3] ,Environmental health ,medicine ,cancer ,Humans ,consumption ,Risk factor ,Life Style ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,VLAG ,Gynecology ,Bladder cancer ,business.industry ,cigarette-smoking ,questionnaire ,colorectal-cancer ,Cancer ,medicine.disease ,Diet ,Urinary Bladder Neoplasms ,Fruit ,business - Abstract
Contains fulltext : 97508.pdf (Publisher’s version ) (Closed access) Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk.
- Published
- 2011
18. Fluid intake and the risk of urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- Author
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Miren Dorronsoro, Antonia Trichopoulou, Laudina Rodríguez, Françoise Clavel-Chapelon, Nadia Slimani, Jonas Manjer, Lars Egevad, Georgia Stasinopulou, Elio Riboli, Esther Molina, Nina Roswall, Philippos Orfanos, Inger T. Gram, Maria Dolores Chirlaque, Petra H.M. Peeters, Kim Overvad, Vittorio Krogh, Naomi E. Allen, Martine M. Ros, Ellen Kampman, Amalia Mattiello, Börje Ljungberg, Rosario Tumino, Fränzel J.B. Van Duijnhoven, Frederike L. Büchner, Paolo Boffetta, Nicholas J. Wareham, Anne Tjønneland, Lambertus A. Kiemeney, Steffen Weikert, Heiner Boeing, Katja K.H. Aben, Paolo Vineis, Aurelio Barricarte, Kay-Tee Khaw, Calogero Saieva, Jenny Chang-Claude, Carlos González, Dominique S. Michaud, Eiliv Lund, Roy Ehrnström, H. Bas Bueno-de-Mesquita, Rudolf Kaaks, Andrew W. Roddam, Ros, M.M., Bas Bueno-De-Mesquita, H.B., Büchner, F.L., Aben, K.K.H., Kampman, E., Egevad, L., Overvad, K., Tjãnneland, A., Roswall, N., Clavel-Chapelon, F., Kaaks, R., Chang-Claude, J., Boeing, H., Weikert, S., Trichopoulou, A., Orfanos, P., Stasinopulou, G., Saieva, C., Krogh, V., Vineis, P., Tumino, R., Mattiello, A., Peeters, P.H.M., Van Duijnhoven, F.J.B., Lund, E., Gram, I.T., Chirlaque, M.D., Barricarte, A., Rodríguez, L., Molina, E., Gonzalez, C., Dorronsoro, M., Manjer, J., Ehrnström, R., Ljungberg, B., Allen, N.E., Roddam, A.W., Khaw, K.-T., Wareham, N., Boffetta, P., Slimani, N., Michaud, D.S., Kiemeney, L.A.L.M., and Riboli, E.
- Subjects
Male ,Cancer Research ,Nutrition and Disease ,urothelial ,food frequency questionnaire ,Aetiology, screening and detection [ONCOL 5] ,carcinoma ,Cohort Studies ,0302 clinical medicine ,Risk Factors ,Voeding en Ziekte ,Epidemiology ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,risk ,Cancer ,disinfection by-products ,Hazard ratio ,Middle Aged ,Prognosis ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Europe ,Prospective ,Oncology ,030220 oncology & carcinogenesis ,Female ,epidemiology ,Fluid ,bladder-cancer ,intake ,Cohort study ,Adult ,medicine.medical_specialty ,life-style ,coffee ,drinking-water ,Drinking ,European ,Beverages ,lower urinary-tract ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,consumption ,Risk factor ,Aged ,VLAG ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Nutrition ,Gynecology ,Investigation ,business.industry ,Proportional hazards model ,Feeding Behavior ,relative validity ,Urinary Bladder Neoplasms ,Fluid Therapy ,business ,EPIC ,Relative validity ,Follow-Up Studies - Abstract
Contains fulltext : 97923.pdf (Publisher’s version ) (Closed access) Results from previous studies investigating the association between fluid intake and urothelial cell carcinomas (UCC) are inconsistent. We evaluated this association among 233,236 subjects in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had adequate baseline information on water and total fluid intake. During a mean follow-up of 9.3 years, 513 first primary UCC occurred. At recruitment, habitual fluid intake was assessed by a food frequency questionnaire. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for energy intake, smoking status, duration of smoking and lifetime intensity of smoking. When using the lowest tertile of intake as reference, total fluid intake was not associated with risk of all UCC (HR 1.12; 95%CI 0.86-1.45, p-trend = 0.42) or with risk of prognostically high-risk UCC (HR 1.28; 95%CI 0.85-1.93, p-trend = 0.27) or prognostically low-risk UCC (HR 0.93; 95%CI 0.65-1.33, p-trend = 0.74). No associations were observed between risk of UCC and intake of water, coffee, tea and herbal tea and milk and other dairy beverages. For prognostically low-risk UCC suggestions of an inverse association with alcoholic beverages and of a positive association with soft drinks were seen. Increased risks were found for all UCC and prognostically low-risk UCC with higher intake of fruit and vegetable juices. In conclusion, total usual fluid intake is not associated with UCC risk in EPIC. The relationships observed for some fluids may be due to chance, but further investigation of the role of all types of fluid is warranted.
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- 2011
19. Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Amalia Mattiello, Anne Tjønneland, Leila Lujan-Barroso, Marina Touillaud, Kim Overvad, Roy Ehrnström, Rudolf Kaaks, H. Bas Bueno-de-Mesquita, Ole Raaschou-Nielsen, Traci Mouw, Frederike L. Büchner, Petra H.M. Peeters, Laudina Rodríguez, Martine M. Ros, Domenico Palli, Eva Ardanaz, Guri Skeie, David Ulmert, Nina Roswall, Jenny Chang-Claude, Carlos A. González, Elio Riboli, Timothy J. Key, Naomi E. Allen, Franco Berrino, Andrew W. Roddam, Lars Egevad, Dominique S. Michaud, Börje Ljungberg, Nerea Larrañaga, Carmen Navarro, Paolo Boffetta, Mazda Jenab, Nadia Slimani, Sheila Bingham, Steffen Weikert, Göran Hallmans, Heiner Boeing, María José Sánchez, Antonia Trichopoulou, Inger T. Gram, Paula Jakszyn, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Paolo Vineis, Christine L. Parr, Lambertus A. Kiemeney, Dimosthenis Zylis, Kay-Tee Khaw, Rosario Tumino, Eleni Oikonomou, Jakszyn, P., González, C.A., Luján-Barroso, L., Ros, M.M., Bueno-de-Mesquita, H.B., Roswall, N., Tjønneland, A.M., Büchner, F.L., Egevad, L., Overvad, K., Raaschou-Nielsen, O., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Touillaud, M.S., Chang-Claude, J., Allen, N.E., Kiemeney, L.A., Key, T.J., Kaaks, R., Boeing, H., Weikert, S., Trichopoulou, A., Oikonomou, E., Zylis, D., Palli, D., Berrino, F., Vineis, P., Tumino, R., Mattiello, A., Peeters, P.H.M., Parr, C.L., Gram, I.T., Skeie, G., Sánchez, M.-J., Larrañaga, N., Ardanaz, E., Navarro, C., Rodríguez, L., Ulmert, D., Ehrnström, R., Hallmans, G., Ljungberg, B., Roddam, A.W., Bingham, S.A., Khaw, K.-T., Slimani, N., Boffetta, P.A., Jenab, M., Mouw, T., Michaud, D.S., and Riboli, E.
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medicine.medical_specialty ,Meat ,Nitrosamines ,Epidemiology ,Aetiology, screening and detection [ONCOL 5] ,Heme ,Gastroenterology ,Molecular epidemiology [NCEBP 1] ,dietary nitrosamine ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,Medicine ,Humans ,Prospective Studies ,Risk factor ,Prospective cohort study ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Bladder cancer ,business.industry ,red meat ,heme iron risk ,Cancer ,medicine.disease ,Surgery ,European Prospective Investigation into Cancer and Nutrition ,Diet ,Europe ,Oncology ,chemistry ,Urinary Bladder Neoplasms ,Red Meat Consumption ,Nitrosamine ,Red meat ,bladder cancer ,business ,Iron, Dietary - Abstract
Background: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI. Results: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99–1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92–1.30 and HR: 0.98; 95% CI: 0.92–1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99–1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk). Conclusions: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 20(3); 555–9. ©2011 AACR.
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- 2011
20. Correction: High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer.
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Topi G, Satapathy SR, Ghatak S, Hellman K, Ek F, Olsson R, Ehrnström R, Lydrup ML, and Sjölander A
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- 2024
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21. High Oestrogen receptor alpha expression correlates with adverse prognosis and promotes metastasis in colorectal cancer.
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Topi G, Satapathy SR, Ghatak S, Hellman K, Ek F, Olsson R, Ehrnström R, Lydrup ML, and Sjölander A
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- Humans, Mice, Animals, Estrogen Receptor alpha, beta Catenin metabolism, Zebrafish metabolism, Wnt Signaling Pathway, Estrogen Receptor beta genetics, Disease Models, Animal, Colonic Neoplasms pathology, Colorectal Neoplasms pathology
- Abstract
In normal colon tissue, oestrogen receptor alpha (ERα) is expressed at low levels, while oestrogen receptor beta (ERβ) is considered the dominant subtype. However, in colon carcinomas, the ERα/β ratio is often increased, an observation that prompted us to further investigate ERα's role in colorectal cancer (CRC). Here, we assessed ERα nuclear expression in 351 CRC patients. Among them, 119 exhibited positive ERα nuclear expression, which was significantly higher in cancer tissues than in matched normal tissues. Importantly, patients with positive nuclear ERα expression had a poor prognosis. Furthermore, positive ERα expression correlated with increased levels of the G-protein coupled cysteinyl leukotriene receptor 1 (CysLT
1 R) and nuclear β-catenin, both known tumour promoters. In mouse models, ERα expression was decreased in Cysltr1-/- CAC (colitis-associated colon cancer) mice but increased in ApcMin/+ mice with wild-type Cysltr1. In cell experiments, an ERα-specific agonist (PPT) increased cell survival via WNT/β-catenin signalling. ERα activation also promoted metastasis in a zebrafish xenograft model by affecting the tight junction proteins ZO-1 and Occludin. Pharmacological blockade or siRNA silencing of ERα limited cell survival and metastasis while restoring tight junction protein expression. In conclusion, these findings highlight the potential of ERα as a prognostic marker for CRC and its role in metastasis., (© 2024. The Author(s).)- Published
- 2024
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22. Combined Estrogen Alpha and Beta Receptor Expression Has a Prognostic Significance for Colorectal Cancer Patients.
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Topi G, Ghatak S, Satapathy SR, Ehrnström R, Lydrup ML, and Sjölander A
- Abstract
We reported that high estrogen receptor beta (ERβ) expression is independently associated with better prognosis in female colorectal cancer (CRC) patients. However, estrogen receptor alpha (ERα) is expressed at very low levels in normal colon mucosa, and its prognostic role in CRC has not been explored. Herein, we investigated the combined role of ERα and ERβ expression in the prognosis of female patients with CRC, which, to the best of our knowledge, is the first study to investigate this topic. A total number of 306 primary CRCs were immunostained for ERα and ERβ expression. A Cox regression model was used to evaluate overall survival (OS) and disease-free survival (DFS). The combined expression of high ERβ + negative ERα correlates with longer OS (HR = 0.23; 95% CI: 0.11-0.45, P <0.0001) and DFS (HR = 0.10; 95% CI: 0.03-0.26, P < 0.0001) and a more favorable tumor outcome, as well as significantly higher expression of antitumorigenic proteins than combined expression of low ERβ + positive ERα. Importantly, we found that low ERβ expression was associated with local recurrence of CRC, whereas ERα expression was correlated with liver metastasis. Overall, our results show that the combined high ERβ + negative ERα expression correlated with a better prognosis for CRC patients. Our results suggest that the combined expression of ERα and ERβ could be used as a predictive combination marker for CRC patients, especially for predicting DFS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Topi, Ghatak, Satapathy, Ehrnström, Lydrup and Sjölander.)
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- 2022
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23. Tumour-suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model.
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Topi G, Satapathy SR, Dash P, Fred Mehrabi S, Ehrnström R, Olsson R, Lydrup ML, and Sjölander A
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- Animals, Antineoplastic Agents pharmacology, Apoptosis, Caco-2 Cells, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Estrogen Receptor beta agonists, Estrogen Receptor beta genetics, Female, Genes, APC, HCT116 Cells, HT29 Cells, Humans, Mice, Inbred C57BL, Mice, Transgenic, Neoplasm Metastasis, Oxazoles pharmacology, Receptors, Leukotriene genetics, Receptors, Leukotriene metabolism, Signal Transduction, Xenograft Model Antitumor Assays, Zebrafish, Cell Movement drug effects, Cell Proliferation drug effects, Colorectal Neoplasms metabolism, Estrogen Receptor beta metabolism
- Abstract
Oestrogen receptor β (ERβ) has been suggested to have anti-proliferative and anti-tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour-promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorectal cancer (CRC) patients. Herein, we investigated the possible anti-tumour effect of ERβ and its selective agonist. CRC patients with high ERβ expression had significantly higher levels of membrane-associated β-catenin, cysteinyl leukotriene receptor 2 (CysLT
2 R), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which have anti-tumour effects, but lower levels of nuclear β-catenin, cysteinyl leukotriene receptor 1 (CysLT1 R), and cyclooxygenase-2 (COX-2), which have tumour-promoting effects. These interesting findings were further supported by two different publicly available CRC mRNA datasets that showed a significant positive correlation between ERβ expression and 15-PGDH and CysLT2 R expression and a negative correlation between ERβ expression and β-catenin, CysLT1 R, and COX-2 expression. We next evaluated ERβ expression in three different colon cancer mouse models; ERβ expression was negatively correlated with tumourigenesis. Furthermore, treatment with the ERβ-agonist ERB-041 reduced CysLT1 R, active β-catenin, and COX-2 levels but increased phospho-β-catenin, CysLT2 R, and 15-PGDH levels in HCT-116, Caco-2, and SW-480 colon cancer cells compared to vehicle-treated cells. Interestingly, ERB-041-treated cells showed significantly decreased migration, survival, and colonosphere formation and increased apoptotic activity, as indicated by increased CASPASE-3 and apoptotic blebs. Finally, patients with low ERβ expression had significantly more distant metastasis at the time of diagnosis than patients with high ERβ expression. Therefore, we studied the effects of ERB-041-treated colon cancer cells in a zebrafish xenograft model. We found significantly less distant metastasis of ERB-041-treated cells compared to vehicle-treated cells. These results further support ERβ's anti-tumour role in CRC and the possible use of its agonist in CRC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)- Published
- 2020
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24. One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.
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Vrieling A, Bueno-De-Mesquita HB, Ros MM, Kampman E, Aben KK, Büchner FL, Jansen EH, Roswall N, Tjønneland A, Boutron-Ruault MC, Cadeau C, Chang-Claude J, Kaaks R, Weikert S, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Sieri S, Palli D, Panico S, Peeters PH, Weiderpass E, Skeie G, Jakszyn P, Chirlaque MD, Ardanaz E, Sánchez MJ, Ehrnström R, Malm J, Ljungberg B, Khaw KT, Wareham NJ, Brennan P, Johansson M, Riboli E, and Kiemeney LA
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- Aged, Biomarkers, Tumor blood, Carcinoma, Transitional Cell blood, Case-Control Studies, Female, Folic Acid administration & dosage, Homocysteine blood, Humans, Male, Middle Aged, Odds Ratio, Prospective Studies, Risk Assessment, Smoking blood, Smoking epidemiology, Urinary Bladder Neoplasms blood, Vitamin B 12 blood, Vitamin B 6 blood, Carcinoma, Transitional Cell epidemiology, Folic Acid blood, Urinary Bladder Neoplasms epidemiology
- Abstract
Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2019
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25. Diagnosing Distal Urethral Carcinomas in Men Might Be Only the Tip of the Iceberg.
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Torbrand C, Håkansson U, Ehrnström R, and Liedberg F
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- Aged, Humans, Male, Neoplasm Invasiveness, Prognosis, Retrospective Studies, Carcinoma, Squamous Cell diagnosis, Penile Neoplasms diagnosis, Urethral Neoplasms diagnosis
- Published
- 2017
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26. Association of the oestrogen receptor beta with hormone status and prognosis in a cohort of female patients with colorectal cancer.
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Topi G, Ehrnström R, Jirström K, Palmquist I, Lydrup ML, and Sjölander A
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- Adult, Aged, Aged, 80 and over, Colorectal Neoplasms etiology, Disease-Free Survival, Female, Hormone Replacement Therapy adverse effects, Humans, Immunohistochemistry, Life Style, Male, Middle Aged, Neoplasm Recurrence, Local metabolism, Prognosis, Risk Factors, Tissue Array Analysis, Colorectal Neoplasms metabolism, Estrogen Receptor beta metabolism
- Abstract
Background: The oestrogen receptor beta (ERβ) is the predominant oestrogen receptor in the normal colon mucosa and has been reported to exert anti-proliferative and pro-apoptotic effects. However, the role of ERβ in colorectal cancer (CRC) progression remains unclear., Aim: To investigate the role of ERβ and its association with hormone status and lifestyle indicators in a female cohort of patients with CRC., Methods: Tissue microarrays of primary CRC tumour samples from 320 female patients were conducted with a monoclonal anti-ERβ antibody. The staining intensity was evaluated using immunohistochemistry. The association of ERβ expression with overall survival, disease-free survival, hormone status and lifestyle was evaluated, and effect estimators with 95% confidence intervals (CIs) were reported., Results: Among the 314 samples with successfully detected ERβ, 182 (58%) had low expression and 132 (42%) had high expression. The Cox multivariate analysis indicated that patients with high ERβ expression had a decreased risk of overall mortality by 50% (hazard ratio [HR], 0.50; CI, 0.30-0.83) and of cancer recurrence by 76% (HR, 0.24; CI, 0.11-0.52) after adjusting for age, tumour-node-metastasis stage and tumour intravascular invasion. Furthermore, high ERβ expression was significantly correlated with shorter breastfeeding time and longer use of hormone replacement therapy. No association was found between ERβ expression and lifestyle indicators., Conclusion: Elevated ERβ expression is independently associated with a better prognosis and hormone status but not lifestyle indicators in female CRC patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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27. Expression of STAT3 in Prostate Cancer Metastases.
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Don-Doncow N, Marginean F, Coleman I, Nelson PS, Ehrnström R, Krzyzanowska A, Morrissey C, Hellsten R, and Bjartell A
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- Adenocarcinoma metabolism, Adenocarcinoma secondary, Autopsy, Bone Neoplasms metabolism, Bone Neoplasms secondary, Humans, Immunohistochemistry, Liver Neoplasms metabolism, Liver Neoplasms secondary, Lymph Nodes metabolism, Lymphatic Metastasis, Male, Neoplasm Metastasis, Phosphoproteins metabolism, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Prostatic Neoplasms, Castration-Resistant metabolism, Prostatic Neoplasms, Castration-Resistant pathology, Receptors, Interleukin-6 metabolism, STAT3 Transcription Factor metabolism, Transcriptome, Adenocarcinoma genetics, Benzamides metabolism, Bone Neoplasms genetics, Liver Neoplasms genetics, Piperidines metabolism, Prostatic Neoplasms, Castration-Resistant genetics, Receptors, Interleukin-6 genetics, STAT3 Transcription Factor genetics
- Abstract
STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC., Patient Summary: We studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
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28. Non-canonical WNT5A signaling up-regulates the expression of the tumor suppressor 15-PGDH and induces differentiation of colon cancer cells.
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Mehdawi LM, Prasad CP, Ehrnström R, Andersson T, and Sjölander A
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- Animals, Breast Neoplasms genetics, Breast Neoplasms pathology, Caco-2 Cells, Colonic Neoplasms drug therapy, Colonic Neoplasms pathology, Female, Gene Expression Regulation, Neoplastic, HT29 Cells, Humans, Hydroxyprostaglandin Dehydrogenases metabolism, Kaplan-Meier Estimate, Mice, Nude, Oligopeptides pharmacology, Oligopeptides therapeutic use, Cell Differentiation genetics, Colonic Neoplasms genetics, Hydroxyprostaglandin Dehydrogenases genetics, Signal Transduction, Up-Regulation genetics, Wnt-5a Protein metabolism
- Abstract
The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme in prostaglandin E
2 catabolism and is down-regulated in colorectal cancer (CRC) tissue. Canonical Wnt signaling is frequently elevated in colon cancers and has been shown to down-regulate 15-PGDH expression. Therefore, we have in the current study investigated if the non-canonical ligand WNT5A relates to increased expression of 15-PGDH in colon cancer cells. In the same cohort of patients, we demonstrated a parallel and significant loss of 15-PGDH and WNT5A protein expression in CRC tissues compared with matched normal colon tissues. Furthermore, patients with low 15-PGDH/WNT5A expression in their tumors showed reduced survival compared with patients with high 15-PGDH/WNT5A expression. To investigate if WNT5A signaling directly affects 15-PGDH expression, we performed in vitro analyses of colon cancer cells (HT-29 and Caco-2). Both cell lines, when treated with recombinant WNT5A (rWNT5A) or Foxy-5, a WNT5A-mimicking peptide, responded by increasing their expression of 15-PGDH mRNA and protein. Our investigations showed that rWNT5A and Foxy-5 induced this increased expression of 15-PGDH through reduced β-catenin signaling as well as increased JNK/AP-1 signaling in colon cancer cells. WNT5A signaling also induced increased 15-PGDH expression in a breast cancer cell line both in vitro and in vivo. In agreement, WNT5A signaling also increased the expression of the differentiation markers sucrose-isomaltase and mucin-2 in colon cancer cells. Our results show that WNT5A signaling regulates 15-PGDH expression, thus uncovering a novel mechanism by which WNT5A acts as a tumor suppressor and suggests that increased 15-PGDH expression could be used as an indicator of a positive response to Foxy-5 in patients treated with this WNT5A agonist., (Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)- Published
- 2016
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29. Anthropometric measures and bladder cancer risk: a prospective study in the EPIC cohort.
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Roswall N, Freisling H, Bueno-de-Mesquita HB, Ros M, Christensen J, Overvad K, Boutron-Ruault MC, Severi G, Fagherazzi G, Chang-Claude J, Kaaks R, Steffen A, Boeing H, Argüelles M, Agudo A, Sánchez MJ, Chirlaque MD, Barricarte Gurrea A, Amiano P, Wareham N, Khaw KT, Bradbury KE, Trichopoulou A, Papatesta HM, Trichopoulos D, Palli D, Pala V, Tumino R, Sacerdote C, Mattiello A, Peeters PH, Ehrnström R, Brennan P, Ferrari P, Ljungberg B, Norat T, Gunter M, Riboli E, Weiderpass E, and Halkjaer J
- Subjects
- Adult, Aged, Aged, 80 and over, Body Mass Index, Female, Humans, Male, Middle Aged, Obesity complications, Obesity epidemiology, Proportional Hazards Models, Prospective Studies, Risk Factors, Smoking, Urinary Bladder Neoplasms complications, Waist Circumference, Waist-Hip Ratio, Young Adult, Anthropometry, Urinary Bladder Neoplasms epidemiology
- Abstract
Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip ratio, waist-height ratio, body mass index (BMI), recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight [1.04 (1.01-1.07) per 5 kilo], BMI [1.05 (1.02-1.08) per 2 units], waist circumference [1.04 (1.01-1.08) per 5 cm], waist-hip ratio (1.07 (1.02-1.13) per 0.05 unit] and waist-height ratio [1.07 (1.01-1.13) per 0.05 unit] in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p = 0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking., (© 2014 UICC.)
- Published
- 2014
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30. N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort.
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Pesch B, Gawrych K, Rabstein S, Weiss T, Casjens S, Rihs HP, Ding H, Angerer J, Illig T, Klopp N, Bueno-de-Mesquita B, Ros MM, Kaaks R, Chang-Claude J, Roswall N, Tjønneland A, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Dossus L, Boeing H, Weikert S, Trichopoulos D, Palli D, Sieri S, Tumino R, Panico S, Quirós JR, González C, Sánchez MJ, Dorronsoro M, Navarro C, Barricarte A, Ljungberg B, Johansson M, Ulmert D, Ehrnström R, Khaw KT, Wareham N, Key TJ, Ferrari P, Romieu I, Riboli E, Brüning T, and Vineis P
- Subjects
- Acetylation, Adult, Aged, Amines analysis, Amines poisoning, Arylamine N-Acetyltransferase genetics, Case-Control Studies, Female, Genotype, Humans, Male, Middle Aged, Phenotype, Polycyclic Aromatic Hydrocarbons analysis, Polycyclic Aromatic Hydrocarbons poisoning, Polymorphism, Single Nucleotide, Risk Factors, Urinary Bladder Neoplasms genetics, Young Adult, Arylamine N-Acetyltransferase metabolism, Occupational Exposure statistics & numerical data, Urinary Bladder Neoplasms enzymology, Urinary Bladder Neoplasms epidemiology
- Abstract
Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition., Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples., Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02-1.84, and OR = 1.50; 95% CI, 1.09-2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81-1.29)., Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking., Impact: Genetic testing for NAT2 would be inappropriate in occupational settings., (©2013 AACR.)
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- 2013
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31. No evidence for shedding of circulating tumor cells to the peripheral venous blood as a result of mammographic breast compression.
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Förnvik D, Andersson I, Dustler M, Ehrnström R, Rydén L, Tingberg A, Zackrisson S, and Aaltonen K
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- Aged, Aged, 80 and over, Compressive Strength, Female, Humans, Lymphatic Metastasis, Middle Aged, Pressure, Tumor Burden, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Mammography adverse effects, Neoplastic Cells, Circulating metabolism
- Abstract
This pilot study aimed to investigate whether mammographic compression procedures might cause shedding of tumor cells into the circulatory system as reflected by circulating tumor cell (CTC) count in peripheral venous blood samples. From March to October 2012, 24 subjects with strong suspicion of breast malignancy were included in the study. Peripheral blood samples were acquired before and after mammography. Enumeration of CTCs in the blood samples was performed using the CellSearch(®) system. The pressure distribution over the tumor-containing breast was measured using thin pressure sensors. The median age was 66.5 years (range, 51-87 years). In 22 of the 24 subjects, breast cancer was subsequently confirmed. The difference between the average mean tumor pressure 6.8 ± 5.3 kPa (range, 1.0-22.5 kPa) and the average mean breast pressure 3.4 ± 1.6 kPa (range, 1.5-7.1 kPa) was statistically significant (p < 0.001), confirming that there was increased pressure over the tumor. The median pathological tumor size was 19 mm (range, 9-30 mm). Four subjects (17 %) were CTC positive before compression and two of these (8 %) were also CTC positive after compression. A total of seven CTCs were isolated with a mean size of 8 × 6 μm(2) (range of the longest diameter, 5-12 μm). The study supports the view that mammography is a safe procedure from the point of view of tumor cell shedding to the peripheral blood.
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- 2013
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32. The prognostic significance of Wnt-5a expression in primary breast cancer is extended to premenopausal women.
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Sand-Dejmek J, Ehrnström R, Berglund P, Andersson T, and Ryden L
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- Adult, Antineoplastic Agents therapeutic use, Cell Line, Tumor, Cell Proliferation, Collagen chemistry, Disease-Free Survival, Drug Combinations, Female, Follow-Up Studies, Humans, Immunohistochemistry, Laminin chemistry, Middle Aged, Multicenter Studies as Topic, Neoplasm Invasiveness, Premenopause, Prognosis, Proportional Hazards Models, Proteoglycans chemistry, Randomized Controlled Trials as Topic, Receptors, Estrogen metabolism, Tamoxifen therapeutic use, Tissue Array Analysis, Treatment Outcome, Wnt-5a Protein, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins metabolism, Wnt Proteins metabolism
- Abstract
Wnt-5a protein expression in primary tumors from unselected breast cancer patients has revealed a tumor suppressive function of the protein. However, in vitro experiments on human breast cancer cells have reported contradictory results, indicating both a tumor suppressive and promoting functions of Wnt-5a. This could be due to various functions of Wnt-5a in different subgroups of patients. The unselected cohorts analyzed to date for Wnt-5a protein expression contained few premenopausal patients. The aim of the present investigation was to evaluate the prognostic significance of Wnt-5a protein expression in a cohort of premenopausal women with comprehensive data on biomarkers, molecular subtypes and long-term outcome. In a randomized trial of adjuvant tamoxifen versus no adjuvant treatment, 564 premenopausal primary breast cancer patients were included. The median follow-up time was 14 years. A tumor tissue array was constructed and 361 samples were evaluated for Wnt-5a reactivity by immunohistochemistry. The primary end-point was recurrence-free survival. Wnt-5a protein expression was reduced or lost in 146/361 of tumors and correlated to younger age, estrogen receptor (ER) negativity and triple-negative phenotype. Wnt-5a was a prognostic factor in the whole cohort (p = 0.003). In patients with ER-positive tumors, Wnt-5a was an independent positive prognostic marker (HR 0.51 95% CI: 0.33-0.78 p = 0.002) and HER2 a negative prognostic marker (HR 2.84 95% CI: 1.51-5.31, p = 0.001) in a Cox multivariate analysis adjusted for standard prognostic markers and tamoxifen treatment. In the ER-negative subset, Wnt-5a added no prognostic information. In a subgroup analysis, Wnt-5a was significantly associated with better prognosis in patients with Luminal A tumors (p = 0.04). Conclusively, our results suggest that loss of Wnt-5a is a valuable prognostic marker in premenopausal breast cancer patients in particular in patients with ER-positive tumors and out-performed conventional prognostic factors in this subset of patients.
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- 2013
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33. Rapid morphological changes and loss of collagen following experimental acute colonic obstruction.
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Krarup PM, Rehn M, Sand-Dejmek J, Ehrnström R, Ågren MS, and Syk I
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- Animals, Colon metabolism, Immunohistochemistry, Intestinal Obstruction chemically induced, Male, Rats, Rats, Sprague-Dawley, Time Factors, Water, Collagen metabolism, Colon pathology, Intestinal Obstruction metabolism, Intestinal Obstruction pathology
- Abstract
Purpose: Anastomosis of an acutely obstructed colon is associated with an increased risk of dehiscence. In experimental models, acute obstruction decreases collagen in the colonic wall, but the time course and propagation along the colon of the biochemical changes are unknown. Furthermore, there is a paucity of information on the correlation between these biochemical changes and histological features., Methods: Forty male Sprague Dawley rats were subjected to partial obstruction by placing a silicone ring around the left colon 30 mm above the reflection. Obstruction was maintained for 0, 1, 2, 3 or 4 days. Samples from five different locations along the colon were analysed on circumference, tissue water content, collagen concentration and histomorphology. Neutrophil and macrophage infiltration was characterized immunohistochemically., Results: The colonic circumference and water content increased (p < 0.001), while the collagen concentration decreased by 48 % (p < 0.01) proximal to the obstruction already after 1 day. The degree of dilation and collagen reduction did not change significantly over the subsequent 3 days of obstruction, whereas the water content normalized by day 3. Mucosal and submucosal oedema and the relative neutrophil infiltration were highest after 1 day in the colonic segment proximal to the stenosis while the macrophage population continued to increase to day 4. Muscular necrosis in addition to ganglionitis and neuritis in the nervous plexus increased with duration of obstruction., Conclusions: The pronounced and rapid changes of the composition of cells and the extracellular matrix of the colonic wall following acute obstruction may be of guidance for present surgical treatments and future pharmacological interventions.
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- 2013
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34. Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.
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Allen NE, Appleby PN, Key TJ, Bueno-de-Mesquita HB, Ros MM, Kiemeney LA, Tjønneland A, Roswall N, Overvad K, Weikert S, Boeing H, Chang-Claude J, Teucher B, Panico S, Sacerdote C, Tumino R, Palli D, Sieri S, Peeters P, Quirós JR, Jakszyn P, Molina-Montes E, Chirlaque MD, Ardanaz E, Dorronsoro M, Khaw KT, Wareham N, Ljungberg B, Hallmans G, Ehrnström R, Ericson U, Gram IT, Parr CL, Trichopoulou A, Karapetyan T, Dilis V, Clavel-Chapelon F, Boutron-Ruault MC, Fagherrazzi G, Romieu I, Gunter MJ, and Riboli E
- Subjects
- Adult, Aged, Aged, 80 and over, Body Mass Index, Calcium, Dietary administration & dosage, Diet, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Dietary Fiber administration & dosage, Europe epidemiology, Female, Humans, Male, Middle Aged, Nutritional Status, Prospective Studies, Risk Assessment, Risk Factors, Smoking, Surveys and Questionnaires, Urinary Bladder pathology, Dietary Proteins administration & dosage, Feeding Behavior, Meat, Plant Proteins, Dietary administration & dosage, Urinary Bladder Neoplasms epidemiology, Urinary Bladder Neoplasms etiology
- Abstract
Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed., (Copyright © 2012 UICC.)
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- 2013
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35. Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up.
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Gonzalez CA, Lujan-Barroso L, Bueno-de-Mesquita HB, Jenab M, Duell EJ, Agudo A, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Touillaud M, Teucher B, Kaaks R, Boeing H, Steffen A, Trichopoulou A, Roukos D, Karapetyan T, Palli D, Tagliabue G, Mattiello A, Tumino R, Ricceri F, Siersema PD, Numans ME, Peeters PP, Parr CL, Skeie G, Lund E, Quirós JR, Sánchez-Cantalejo E, Navarro C, Barricarte A, Dorronsoro M, Ehrnström R, Regner S, Khaw KT, Wareham N, Key TJ, Crowe FL, Blaker H, Romieu I, and Riboli E
- Subjects
- Adult, Aged, Calibration, Diet, Europe epidemiology, Female, Follow-Up Studies, Humans, Life Style, Male, Middle Aged, Risk Factors, Adenocarcinoma epidemiology, Fruit, Stomach Neoplasms epidemiology, Vegetables
- Abstract
In a previous European prospective investigation into cancer and nutrition (EPIC) analysis, we found an inverse association between total intake of vegetables, onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of fruit and vegetables (F&V), based on a longer follow-up and twice the number of GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11 years of follow-up. Information on diet and lifestyle was collected at baseline. A calibration study in a subsample was used to correct for dietary measurement errors. When comparing the highest vs. lowest quintile of intake, we found an inverse association between total intake of V&F and GC risk [hazard ratio (HR) 0.77; 95% confidence interval (CI) 0.57-1.04; p for trend 0.02], between fresh fruit and risk of the diffuse type (HR 0.59; 95% CI 0.36-0.97; p for trend 0.03) and an inverse association between citrus fruit and risk of cardia cancer (HR 0.61; 95% CI 0.38-1.00, p for trend 0.01). Although calibration revealed somewhat stronger inverse associations, none of the risks reached statistical significance. There was no association between total or specific vegetables intake and GC risk. The inverse association between fresh fruit and citrus fruits and risk of GC seems to be restricted to smokers and the Northern European countries. Fresh fruit and citrus fruit consumption may protect against diffuse and cardia GC, respectively., (Copyright © 2012 UICC.)
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- 2012
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36. Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.
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Ros MM, Bueno-de-Mesquita HB, Kampman E, Aben KK, Büchner FL, Jansen EH, van Gils CH, Egevad L, Overvad K, Tjønneland A, Roswall N, Boutron-Ruault MC, Kvaskoff M, Perquier F, Kaaks R, Chang-Claude J, Weikert S, Boeing H, Trichopoulou A, Lagiou P, Dilis V, Palli D, Pala V, Sacerdote C, Tumino R, Panico S, Peeters PH, Gram IT, Skeie G, Huerta JM, Barricarte A, Quirós JR, Sánchez MJ, Buckland G, Larrañaga N, Ehrnström R, Wallström P, Ljungberg B, Hallmans G, Key TJ, Allen NE, Khaw KT, Wareham N, Brennan P, Riboli E, and Kiemeney LA
- Subjects
- Adult, Aged, Ascorbic Acid therapeutic use, Carcinoma, Transitional Cell epidemiology, Carcinoma, Transitional Cell etiology, Carcinoma, Transitional Cell prevention & control, Carotenoids therapeutic use, Case-Control Studies, Cohort Studies, Europe epidemiology, Female, Follow-Up Studies, Humans, Incidence, Lutein blood, Lutein therapeutic use, Male, Middle Aged, Papilloma blood, Papilloma epidemiology, Papilloma etiology, Papilloma prevention & control, Prospective Studies, Urinary Bladder Neoplasms epidemiology, Urinary Bladder Neoplasms etiology, Urinary Bladder Neoplasms prevention & control, Ascorbic Acid blood, Carcinoma, Transitional Cell blood, Carotenoids blood, Diet adverse effects, Urinary Bladder Neoplasms blood, Urothelium pathology
- Abstract
Background: Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status., Objective: We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition., Design: A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity., Results: UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma β-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC., Conclusions: Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC.
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- 2012
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37. Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
- Author
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Duell EJ, Sala N, Travier N, Muñoz X, Boutron-Ruault MC, Clavel-Chapelon F, Barricarte A, Arriola L, Navarro C, Sánchez-Cantalejo E, Quirós JR, Krogh V, Vineis P, Mattiello A, Tumino R, Khaw KT, Wareham N, Allen NE, Peeters PH, Numans ME, Bueno-de-Mesquita HB, van Oijen MG, Bamia C, Benetou V, Trichopoulos D, Canzian F, Kaaks R, Boeing H, Bergmann MM, Lund E, Ehrnström R, Johansen D, Hallmans G, Stenling R, Tjønneland A, Overvad K, Ostergaard JN, Ferrari P, Fedirko V, Jenab M, Nesi G, Riboli E, and González CA
- Subjects
- Alcohol Drinking metabolism, Alcoholism enzymology, Alcoholism genetics, Alleles, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Genetic Loci, Haplotypes genetics, Humans, Isoenzymes, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Stomach Neoplasms enzymology, Stomach Neoplasms etiology, Alcohol Dehydrogenase genetics, Alcohol Drinking genetics, Aldehyde Dehydrogenase genetics, Stomach Neoplasms genetics, White People genetics
- Abstract
Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (OR(T v C) = 0.59; 95% CI = 0.38-0.91 and OR(T v C) = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (OR(A+T) = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (<5 g/day: OR(A) = 0.89, 95% CI = 0.57-1.39; ≥5 g/day: OR(A) = 1.45, 95% CI = 1.08-1.94, P-value = 0.05). The association was also modified by ethanol intake from beer. A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025. Additional population-based studies are needed to confirm our results.
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- 2012
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38. Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).
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Balassiano K, Lima S, Jenab M, Overvad K, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Canzian F, Kaaks R, Boeing H, Meidtner K, Trichopoulou A, Laglou P, Vineis P, Panico S, Palli D, Grioni S, Tumino R, Lund E, Bueno-de-Mesquita HB, Numans ME, Peeters PH, Ramon Quirós J, Sánchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Hallmans G, Stenling R, Ehrnström R, Regner S, Allen NE, Travis RC, Khaw KT, Offerhaus GJ, Sala N, Riboli E, Hainaut P, Scoazec JY, Sylla BS, Gonzalez CA, and Herceg Z
- Subjects
- Aged, Europe epidemiology, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Molecular Epidemiology, Neoplasm Proteins blood, Neoplasm Proteins genetics, Prospective Studies, Stomach Neoplasms blood, Stomach Neoplasms epidemiology, Stomach Neoplasms pathology, DNA Methylation, Stomach Neoplasms genetics
- Abstract
Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological sub-type and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
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- 2011
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39. Cysteinyl leukotriene receptor expression pattern affects migration of breast cancer cells and survival of breast cancer patients.
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Magnusson C, Liu J, Ehrnström R, Manjer J, Jirström K, Andersson T, and Sjölander A
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Hormonal pharmacology, Breast Neoplasms pathology, Cell Line, Tumor, Female, Humans, Immunohistochemistry, Middle Aged, Polymerase Chain Reaction, Receptors, Leukotriene genetics, Tamoxifen pharmacology, Transcription, Genetic drug effects, Breast Neoplasms metabolism, Neoplasm Metastasis, Receptors, Leukotriene metabolism, Survival Analysis
- Abstract
The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. Here, we have determined the expression of proinflammatory cysteinyl leukotriene receptors (CysLTRs) in breast tumor tissue and their signaling effect on breast cancer cell functions related to tumor progression. Patients with breast tumors characterized by high CysLT(1)R and low CysLT(2)R expression levels exhibited increased risk of cancer-induced death in univariate analysis for both the total patient group (hazard ratio [HR] = 2.88, 95% confidence interval [CI] = 1.11-7.41), as well as patients with large (>20 mm) tumors (HR = 5.08, 95% CI = 1.39-18.5). Multivariate analysis revealed that patients with large tumors exhibiting high CysLT(1)R and low CysLT(2)R expression levels had a significantly reduced survival, also when adjusted for established prognostic parameters (HR = 7.51, 95% CI = 1.83-30.8). In patients with large (>20 mm) tumors, elevated CysLT(2)R expression predicted an improved 5-year survival (log-rank test p = 0.04). Surprisingly, for longer time periods, this prognostic value was lost. This disappearance coincided with the termination of hormonal treatment. Tamoxifen preserved and even induced transcription of CysLT(2)R, but not CysLT(1)R, in estrogene receptor-positive MCF-7 breast cancer cells. This elevated CysLT(2)R expression decreased, even below the level of untreated cells, when tamoxifen was withdrawn. CysLT(2)R signaling reduced MCF-7 cell migration, but had no effect on either proliferation or apoptosis. Our data indicate that low CysLT(1)R together with high CysLT(2)R expression levels might be useful parameters in prognostication and treatment stratification of breast cancer patients., (Copyright © 2010 UICC.)
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- 2011
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40. Variety in vegetable and fruit consumption and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition.
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Büchner FL, Bueno-de-Mesquita HB, Ros MM, Kampman E, Egevad L, Overvad K, Tjønneland A, Roswall N, Clavel-Chapelon F, Boutron-Ruault MC, Touillaud M, Kaaks R, Chang-Claude J, Boeing H, Weikert S, Trichopoulou A, Naska A, Benetou V, Palli D, Sieri S, Vineis P, Tumino R, Panico S, van Duijnhoven FJ, Peeters PH, van Gils CH, Lund E, Gram IT, Sánchez MJ, Jakszyn P, Larrañaga N, Ardanaz E, Navarro C, Rodríguez L, Manjer J, Ehrnström R, Hallmans G, Ljungberg B, Key TJ, Allen NE, Khaw KT, Wareham N, Slimani N, Jenab M, Boffetta P, Kiemeney LA, and Riboli E
- Subjects
- Diet, Europe, Female, Humans, Life Style, Male, Prospective Studies, Risk Factors, Fruit, Urinary Bladder Neoplasms epidemiology, Vegetables
- Abstract
Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk., (Copyright © 2010 UICC.)
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- 2011
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41. Fluid intake and the risk of urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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Ros MM, Bas Bueno-de-Mesquita HB, Büchner FL, Aben KK, Kampman E, Egevad L, Overvad K, Tjønneland A, Roswall N, Clavel-Chapelon F, Kaaks R, Chang-Claude J, Boeing H, Weikert S, Trichopoulou A, Orfanos P, Stasinopulou G, Saieva C, Krogh V, Vineis P, Tumino R, Mattiello A, Peeters PH, van Duijnhoven FJ, Lund E, Gram IT, Chirlaque MD, Barricarte A, Rodríguez L, Molina E, Gonzalez C, Dorronsoro M, Manjer J, Ehrnström R, Ljungberg B, Allen NE, Roddam AW, Khaw KT, Wareham N, Boffetta P, Slimani N, Michaud DS, Kiemeney LA, and Riboli E
- Subjects
- Adult, Aged, Beverages, Cohort Studies, Europe epidemiology, Feeding Behavior, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Urinary Bladder Neoplasms etiology, Urinary Bladder Neoplasms prevention & control, Drinking, Fluid Therapy, Urinary Bladder Neoplasms epidemiology
- Abstract
Results from previous studies investigating the association between fluid intake and urothelial cell carcinomas (UCC) are inconsistent. We evaluated this association among 233,236 subjects in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had adequate baseline information on water and total fluid intake. During a mean follow-up of 9.3 years, 513 first primary UCC occurred. At recruitment, habitual fluid intake was assessed by a food frequency questionnaire. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for energy intake, smoking status, duration of smoking and lifetime intensity of smoking. When using the lowest tertile of intake as reference, total fluid intake was not associated with risk of all UCC (HR 1.12; 95%CI 0.86-1.45, p-trend = 0.42) or with risk of prognostically high-risk UCC (HR 1.28; 95%CI 0.85-1.93, p-trend = 0.27) or prognostically low-risk UCC (HR 0.93; 95%CI 0.65-1.33, p-trend = 0.74). No associations were observed between risk of UCC and intake of water, coffee, tea and herbal tea and milk and other dairy beverages. For prognostically low-risk UCC suggestions of an inverse association with alcoholic beverages and of a positive association with soft drinks were seen. Increased risks were found for all UCC and prognostically low-risk UCC with higher intake of fruit and vegetable juices. In conclusion, total usual fluid intake is not associated with UCC risk in EPIC. The relationships observed for some fluids may be due to chance, but further investigation of the role of all types of fluid is warranted., (Copyright © 2010 UICC.)
- Published
- 2011
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42. Red meat, dietary nitrosamines, and heme iron and risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).
- Author
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Jakszyn P, González CA, Luján-Barroso L, Ros MM, Bueno-de-Mesquita HB, Roswall N, Tjønneland AM, Büchner FL, Egevad L, Overvad K, Raaschou-Nielsen O, Clavel-Chapelon F, Boutron-Ruault MC, Touillaud MS, Chang-Claude J, Allen NE, Kiemeney LA, Key TJ, Kaaks R, Boeing H, Weikert S, Trichopoulou A, Oikonomou E, Zylis D, Palli D, Berrino F, Vineis P, Tumino R, Mattiello A, Peeters PH, Parr CL, Gram IT, Skeie G, Sánchez MJ, Larrañaga N, Ardanaz E, Navarro C, Rodríguez L, Ulmert D, Ehrnström R, Hallmans G, Ljungberg B, Roddam AW, Bingham SA, Khaw KT, Slimani N, Boffetta PA, Jenab M, Mouw T, Michaud DS, and Riboli E
- Subjects
- Europe epidemiology, Heme metabolism, Humans, Iron, Dietary metabolism, Nitrosamines metabolism, Nitrosamines poisoning, Prospective Studies, Risk Factors, Urinary Bladder Neoplasms etiology, Diet, Iron, Dietary administration & dosage, Meat, Nitrosamines administration & dosage, Urinary Bladder Neoplasms epidemiology
- Abstract
Background: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI., Results: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99-1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92-1.30 and HR: 0.98; 95% CI: 0.92-1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99-1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk)., Conclusions: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk., (©2011 AACR.)
- Published
- 2011
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43. Elevated level of Wnt5a protein in localized prostate cancer tissue is associated with better outcome.
- Author
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Syed Khaja AS, Helczynski L, Edsjö A, Ehrnström R, Lindgren A, Ulmert D, Andersson T, and Bjartell A
- Subjects
- Aged, Humans, Immunohistochemistry, Ki-67 Antigen metabolism, Male, Middle Aged, Receptors, Androgen metabolism, Vascular Endothelial Growth Factor A metabolism, Wnt-5a Protein, Prostatic Neoplasms metabolism, Proto-Oncogene Proteins metabolism, Wnt Proteins metabolism
- Abstract
Background: Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays an important role in cancer development and progression. Previous studies report that Wnt5a is upregulated in prostate cancer and suggested that Wnt5a affects migration and invasion of prostate tumor cell. This study aimed to evaluate the prognostic value of Wnt5a protein expression in prostate cancer tissue and its potential to predict outcome after radical prostatectomy in patients with localized prostate cancer., Methodology and Results: Immunohistochemical analysis of a tissue microarray containing prostate specimens of 503 patients with localized prostate cancer showed significantly higher Wnt5a protein expression in cancer compared to benign cores from the same patients (p<0.0001). Patients with high expression of Wnt5a protein had significantly better outcome in terms of time to biochemical recurrence compared to patients with low expression levels (p = 0.001, 95%CI 1.361-3.570, Hazard's ratio 2.204). A combination of high Wnt5a expression with low levels of Ki-67 or androgen receptor expression had even better outcome compared to all other groups. Furthermore, we found that Wnt5a expression significantly correlated with VEGF and with Ki-67 and androgen receptor expression, although not highly significant. In vitro, we demonstrated that recombinant Wnt5a decreased invasion of 22Rv1 and DU145 cells and that siRNA knockdown of endogenous Wnt5a protein led to increased invasion of 22Rv1 and LNCaP cells., Conclusion: We demonstrate that preserved overexpression of Wnt5a protein in patients with localized prostate cancer predicts a favorable outcome after surgery. This finding together with our in vitro data demonstrating the ability of Wnt5a to impair the invasive properties of prostate cancer cells, suggests a tumor suppressing effect of Wnt5a in localized prostate cancer. These results indicate that Wnt5a can be used as a predictive marker and that it also is a plausible therapeutic target for treatment of localized prostate cancer.
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- 2011
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44. Regulation of cysteinyl leukotriene receptor 2 expression--a potential anti-tumor mechanism.
- Author
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Magnusson C, Bengtsson AM, Liu M, Liu J, Ceder Y, Ehrnström R, and Sjölander A
- Subjects
- Base Sequence, Binding Sites, Caco-2 Cells, Cell Differentiation drug effects, E-Box Elements genetics, Epidermal Growth Factor pharmacology, ErbB Receptors metabolism, Genes, Reporter genetics, Humans, Interferon Regulatory Factor-7 metabolism, Interferon-alpha pharmacology, Luciferases metabolism, Molecular Sequence Data, Promoter Regions, Genetic genetics, Receptors, Leukotriene metabolism, Signal Transduction drug effects, Snail Family Transcription Factors, Transcription Factors metabolism, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Gene Expression Regulation, Neoplastic drug effects, Receptors, Leukotriene genetics
- Abstract
Background: The cysteinyl leukotrienes receptors (CysLTRs) are implicated in many different pathological conditions, such as inflammation and cancer. We have previously shown that colon cancer patients with high CysLT(1)R and low CysLT(2)R expression demonstrate poor prognosis. Therefore, we wanted to investigate ways for the transcriptional regulation of CysLT(2)R, which still remains to be poorly understood., Methodology/principal Findings: We investigated the potential role of the anti-tumorigenic interferon α (IFN-α) and the mitogenic epidermal growth factor (EGF) on CysLT(2)R regulation using non-transformed intestinal epithelial cell lines and colon cancer cells to elucidate the effects on the CysLT(2)R expression and regulation. This was done using Western blot, qPCR, luciferase reporter assay and a colon cancer patient array. We found a binding site for the transcription factor IRF-7 in the putative promoter region of CysLT(2)R. This site was involved in the IFN-α induced activity of the CysLT(2)R luciferase reporter assay. In addition, IFN-α induced the activity of the differentiation marker alkaline phosphatase along with the expression of mucin-2, which protects the epithelial layer from damage. Interestingly, EGF suppressed both the expression and promoter activity of the CysLT(2)R. E-boxes present in the CysLT(2)R putative promoter region were involved in the suppressing effect. CysLT(2)R signaling was able to suppress cell migration that was induced by EGF signaling., Conclusions/significance: The patient array showed that aggressive tumors generally expressed less IFN-α receptor and more EGFR. Interestingly, there was a negative correlation between CysLT(2)R and EGFR expression. Our data strengthens the idea that there is a protective role against tumor progression for CysLT(2)R and that it highlights new possibilities to regulate the CysLT(2)R.
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- 2011
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45. Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer.
- Author
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Tassidis H, Brokken LJ, Jirström K, Ehrnström R, Pontén F, Ulmert D, Bjartell A, Härkönen P, and Wingren AG
- Subjects
- Aged, Blotting, Western, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation, Disease-Free Survival, Flow Cytometry, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Interleukin-6 pharmacology, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Predictive Value of Tests, Prognosis, Prostate-Specific Antigen blood, Prostatic Neoplasms immunology, Prostatic Neoplasms pathology, Transfection, Treatment Outcome, Biomarkers, Tumor analysis, Prostatectomy methods, Prostatic Neoplasms enzymology, Prostatic Neoplasms surgery, Protein Tyrosine Phosphatase, Non-Receptor Type 6 analysis
- Abstract
The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here, we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient and stable transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation, whereas in SHP-1-silenced LNCaP cells, IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer.
- Published
- 2010
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46. An increased expression of cysteinyl leukotriene 2 receptor in colorectal adenocarcinomas correlates with high differentiation.
- Author
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Magnusson C, Ehrnström R, Olsen J, and Sjölander A
- Subjects
- Apoptosis physiology, Caco-2 Cells, Cell Differentiation physiology, Cell Growth Processes physiology, Humans, Membrane Proteins metabolism, Receptors, Leukotriene metabolism, Resting Phase, Cell Cycle physiology, Adenocarcinoma metabolism, Adenocarcinoma pathology, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Membrane Proteins biosynthesis, Receptors, Leukotriene biosynthesis
- Abstract
Increased levels of inflammatory mediators such as cysteinyl leukotrienes (CysLT) have been found in and around tumors. These data, along with our previous observation that the G-protein-coupled receptor CysLT(1)R, which signals survival and proliferation, is up-regulated in colon cancer, suggest an important role for CysLT(1)R in tumor development. The objective of this study was to examine the expression and function of the low-affinity CysLT2 receptor (CysLT2R) in colon cancer. We found lower expression levels of CysLT2R compared with CysLT(1)R in cancer cell lines as well as clinical tumor material. Interestingly, CysLT2R, like CysLT(1)R, was found to be one of few G-protein-coupled receptors that are located both at the plasma membrane and the nuclear membrane. No effect of CysLT2R signaling on cell proliferation was observed, nor was there a correlation between CysLT2R and different proliferation markers such as Ki-67 and cyclooxygenase-2 in the tumor material. Instead, we found that activation of this receptor in colon cancer cells led to cellular differentiation similar to the effects of butyrate treatment. In accordance with this finding, we found that reduced expression of CysLT2R in colon cancer was associated with poor prognosis. We report the novel finding that CysLT2R signaling leads to terminal differentiation of colon carcinoma cells and growth inhibition, and that its expression is relatively high in less malignant forms of colon cancer. These data suggest that the balance between these two receptors is important for tumor progression and disease outcome.
- Published
- 2007
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47. Primary seminal vesicle carcinoma detected at transurethral resection of prostate.
- Author
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Egevad L, Ehrnström R, Håkansson U, and Grabe M
- Subjects
- Aged, Humans, Male, Carcinoma diagnosis, Genital Neoplasms, Male diagnosis, Prostatectomy, Seminal Vesicles
- Abstract
We present a case of primary seminal vesicle carcinoma detected at transurethral resection. The clinical presentation, radiologic findings, and pathologic features of these tumors are reviewed. Grossly, seminal vesicle carcinoma is poorly circumscribed and solid or solid/cystic and may be misinterpreted as an abscess or hemorrhage on radiologic examination. Although a definitive diagnosis often cannot be given until after complete resection, we describe the findings indicative of seminal vesicle origin, including papillary histologic architecture, sometimes with mucinous differentiation, and a characteristic immunophenotype positive for CA-125 and cytokeratin 7, but negative for prostate-specific antigen and cytokeratin 20.
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- 2007
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48. Miniaturization and integration: challenges and breakthroughs in microfluidics.
- Author
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Ehrnström R
- Published
- 2002
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49. An experimental study of gastric stump carcinoma in Wistar rats.
- Author
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Ehrnström R, Lindström CG, Arvidsson S, Sternby NH, Nilsson E, and Ehrnström YM
- Subjects
- Acetates, Acetic Acid, Adenocarcinoma chemically induced, Animals, Disease Models, Animal, Male, Rats, Rats, Wistar, Stomach Neoplasms chemically induced, Adenocarcinoma pathology, Gastric Stump pathology, Stomach Neoplasms pathology
- Abstract
The risk of gastric stump carcinoma is increased 15-20 years after gastric resection for benign disease. Reflux of duodenal juice, bacterial overgrowth and formation of N-nitroso compounds are possible etiological factors. There is a geographical variation in the incidence of gastric cancer, possibly explained by differences in food intake. Experimentally it is possible to induce gastric stump carcinoma in rats without the addition of exogenous carcinogens. The aim of this study was: 1) to find the incidence of gastric carcinoma in rats subjected to BII resection and followed for 10 months, and 2) to examine if acetic acid, a common dietary factor, could influence the development of gastric carcinoma. Amongst BII-operated male Wistar rats, infiltrating carcinoma was found in 5/20 on a normal diet and in 5/24 exposed to acetic acid (NS). Benign mucosal changes were seen in 12/20 and 16/24 respectively (NS). With the exception of a profound inflammation in one sham-operated animal, no mucosal pathological changes were found in 24 sham-operated and 24 control animals where no operation was performed.
- Published
- 1995
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50. High-performance analytical applications of immobilized metal ion affinity chromatography.
- Author
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Belew M, Yip TT, Andersson L, and Ehrnström R
- Subjects
- Antibodies, Monoclonal isolation & purification, Copper, Imino Acids, Ions, Nickel, Zinc, Chromatography, Affinity methods, Metals, Proteins isolation & purification
- Abstract
The separation of three sets of standard protein mixtures on a high-performance immobilized metal ion affinity chromatography (HP-IMAC) column by elution with linear gradients of imidazole is described. The affinity of the test proteins for the immobilized metal ions follows the order Cu2+ greater than Ni2+ greater than Zn2+. The iminodiacetic acid-Cu2+ column gives the best resolution of all three protein mixtures and is the only immobilized metal ion column that can be used for elution of absorbed proteins with a decreasing pH gradient. An application of HP-IMAC for the separation of monoclonal IgG from mouse ascites fluid is also outlined. This versatile separation method is thus suitable for both analytical and preparative separations of proteins and peptides resulting in high recoveries and good reproducibility. The leakage of immobilized metal ions from the TSK gel chelate-5PW is apparent if the column is eluted by buffers containing low concentrations of (i) glycine or (ii) primary amines at round neutral pH. Considerable amounts of immobilized Zn2+ and Ni2+ ions also leak from the column by washing with buffers of pH 4.5 or lower. However, all three immobilized metal ions are stable toward exposure to low concentrations of imidazole (up to 50 mM) in phosphate buffers between pH 6.5 and 8.0. Adsorbed proteins could thus be eluted conveniently by using linear gradients of imidazole to give reproducible results. Moreover, this elution procedure made it possible to use the IMAC columns for repeated runs without the need for regeneration and recharging of the columns with fresh metal ions after each use.
- Published
- 1987
- Full Text
- View/download PDF
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