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  • 51. Dahm, Christina C.
    et al.
    Gorst-Rasmussen, Anders
    Crowe, Francesca L.
    Roswall, Nina
    Tjonneland, Anne
    Drogan, Dagmar
    Boeing, Heiner
    Teucher, Birgit
    Kaaks, Rudolf
    Adarakis, George
    Zylis, Dimosthenes
    Trichopoulou, Antonia
    Fedirko, Veronika
    Chajes, Veronique
    Jenab, Mazda
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Ricceri, Fulvio
    van Kranen, Henk
    Bueno-de-Mesquita, H. Bas
    Quiros, Jose R.
    Sanchez, Maria-Jose
    Lujan-Barroso, Leila
    Larranaga, Nerea
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. The Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Khaw, Kay-Tee
    Wareham, Nick
    Wark, Petra A.
    Norat, Teresa
    Riboli, Elio
    Key, Tim J.
    Overvad, Kim
    Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition2012Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, nr 6, s. 1354-1361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. Objective: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. Design: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. Results: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). Conclusion: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology. Am J Clin Nutr 2012;96:1354-61.

  • 52. Danneman, Daniela
    et al.
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Bratt, Ola
    Loeb, Stacy
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, nr 1, s. 50-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 53. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97 168 men2015Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, nr 2, s. 248-255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer. Patients and Methods: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed. Results: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned. Conclusions: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 54. Duggan, David
    et al.
    Zheng, Siqun L
    Knowlton, Michele
    Benitez, Debbie
    Dimitrov, Latchezar
    Wiklund, Fredrik
    Robbins, Christiane
    Isaacs, Sarah D
    Cheng, Yu
    Li, Ge
    Sun, Jielin
    Chang, Bao-Li
    Marovich, Leslie
    Wiley, Kathleen E
    Bälter, Katarina
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Adami, Hans-Olov
    Gielzak, Marta
    Yan, Guifang
    Sauvageot, Jurga
    Liu, Wennuan
    Kim, Jin Woo
    Bleecker, Eugene R
    Meyers, Deborah A
    Trock, Bruce J
    Partin, Alan W
    Walsh, Patrick C
    Isaacs, William B
    Grönberg, Henrik
    Xu, Jianfeng
    Carpten, John D
    Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP.2007Ingår i: J Natl Cancer Inst, ISSN 1460-2105, Vol. 99, nr 24, s. 1836-44Artikel i tidskrift (Refereegranskat)
  • 55.
    Edlinger, M.
    et al.
    Medical University Innsbruck, Innsbruck, Austria.
    Bjorge, T.
    University of Bergen, Bergen, Norway; Norwegian Institute of Public Health, Oslo, Norway.
    Manjer, J.
    Skåne University Hospital Malmö and Lund University, Malmö, Sweden.
    Stattin, Pär
    Ulmer, H.
    Umeå universitet.
    Metabolic syndrome and risk of brain tumour in a large population-based cohort study2011Ingår i: IEA World Congress of Epidemiology, 7–11 August 2011, Edinburgh International Conference Centre, Edinburgh, Scotland: Programme and abstracts, 2011, Vol. 65Konferensbidrag (Refereegranskat)
    Abstract [en]

    Background: There are few established determinants of brain tumour. We assessed among adults the risk of brain tumour in relation to metabolic syndrome factors.

    Methods: 580 000 subjects from Sweden, Austria, and Norway were followed for a median of 10 years (Me-Can). Brain tumour information was obtained from national cancer registries. The factors of metabolic syndrome, body mass index, blood pressure, and blood levels of glucose, cholesterol, and triglycerides, were analysed in quintiles and for transformed z-scores (mean of 0 and SD of 1). Cox proportional hazards regression models were applied, stratified by cohort and corrected for measurement error.

    Results: In total 1312 primary brain tumours were diagnosed during follow-up, predominantly high-grade glioma (n=436) and meningioma (n=348). For meningioma, the HR was increased for systolic blood pressure (HR=1.27 per unit SD, 95% CI 1.03 to 1.57), for diastolic blood pressure (HR=1.29, 95% CI 1.04 to 1.58), and for the combined metabolic syndrome score (HR=1.31, 95% CI 1.11 to 1.54). For high-grade glioma the risk was increased for diastolic blood pressure (HR=1.23, 95% CI 1.01 to 1.50) and triglycerides (HR=1.35, 95% CI 1.05 to 1.72). For both meningioma and high-grade glioma, the risk was more than doubled in the fifth quintiles of diastolic blood pressure compared to the first quintile. For systolic blood pressure the meningioma risk was even larger.

    Conclusion: Increased blood pressure was related to risk of brain tumour, particularly of meningiomas.

  • 56. Edlinger, Michael
    et al.
    Strohmaier, Susanne
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bjørge, Tone
    Manjer, Jonas
    Borena, Wegene T
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Engeland, Anders
    Tretli, Steinar
    Concin, Hans
    Nagel, Gabriele
    Selmer, Randi
    Johansen, Dorthe
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ulmer, Hanno
    Blood pressure and other metabolic syndrome factors and risk of brain tumour in the large population-based Me-Can cohort study2012Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, nr 2, s. 290-296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:: Brain tumour has few established determinants. We assessed to which extent risk of brain tumour was related to metabolic syndrome factors in adults. METHODS:: In the Me-Can project, 580 000 individuals from Sweden, Austria, and Norway were followed for a median of 10 years after baseline measurement. Data on brain tumours were obtained from national cancer registries. The factors of metabolic syndrome (BMI, SBP and DBP, and blood levels of glucose, cholesterol, and triglycerides), separately and combined, were analysed in quintiles and for transformed z-scores (mean transformed to 0 and standard deviation to 1). Cox proportional hazards multivariate regression models were used, with corrections for measurement error. RESULTS:: During follow-up, 1312 primary brain tumours were diagnosed, predominantly meningioma (n = 348) and high-grade glioma (n = 436). For meningioma, the hazard ratio was increased for z-scores of SBP [hazard ratio = 1.27 per unit standard deviation, 95% confidence interval (CI) 1.03-1.57], of DBP (hazard ratio = 1.29, 95% CI 1.04-1.58), and of the combined metabolic syndrome score (hazard ratio = 1.31, 95% CI 1.11-1.54). An increased risk of high-grade glioma was found for DBP (hazard ratio = 1.23, 95% CI 1.01-1.50) and triglycerides (hazard ratio = 1.35, 95% CI 1.05-1.72). For both meningioma and high-grade glioma, the risk was more than double in the fifth quintiles of DBP compared to the lowest quintile. For meningioma this risk was even larger for SBP. CONCLUSION:: Increased blood pressure was associated with risk of brain tumours, especially of meningiomas.

  • 57. Eloranta, Sandra
    et al.
    Adolfsson, Jan
    Lambert, Paul C.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Akre, Olof
    Andersson, Therese M-L.
    Dickman, Paul W.
    How can we make cancer survival statistics more useful for patients and clinicians: an illustration using localized prostate cancer in Sweden2013Ingår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 24, nr 3, s. 505-515Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies of cancer patient survival typically report relative survival or cause-specific survival using data from patients diagnosed many years in the past. From a risk-communication perspective, such measures are suboptimal for several reasons; their interpretation is not transparent for non-specialists, competing causes of death are ignored and the estimates are unsuitable to predict the outcome of newly diagnosed patients. In this paper, we discuss the relative merits of recently developed alternatives to traditionally reported measures of cancer patient survival. In a relative survival framework, using a period approach, we estimated probabilities of death in the presence of competing risks. To illustrate the methods, we present estimates of survival among 23,353 initially untreated, or hormonally treated men with intermediate- or high-risk localized prostate cancer using Swedish population-based data. Among all groups of newly diagnosed patients, the probability of dying from prostate cancer, accounting for competing risks, was lower compared to the corresponding estimates where competing risks were ignored. Accounting for competing deaths was particularly important for patients aged more than 70 years at diagnosis in order to avoid overestimating the risk of dying from prostate cancer. We argue that period estimates of survival, accounting for competing risks, provide the tools to communicate the actual risk that cancer patients, diagnosed today, face to die from their disease. Such measures should offer a more useful basis for risk communication between patients and clinicians and we advocate their use as means to answer prognostic questions.

  • 58. FitzGerald, L. M.
    et al.
    Zhao, S.
    Leonardson, A.
    Geybels, M. S.
    Kolb, S.
    Lin, D. W.
    Wright, J. L.
    Eeles, R.
    Kote-Jarai, Z.
    Govindasami, K.
    Giles, G. G.
    Southey, M. C.
    Schleutker, J.
    Tammela, T. L.
    Sipeky, C.
    Penney, K. L.
    Stampfer, M. J.
    Gronberg, H.
    Wiklund, F.
    Stattin, P.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hugosson, J.
    Karyadi, D. M.
    Ostrander, E. A.
    Feng, Z.
    Stanford, J. L.
    Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases2018Ingår i: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 21, nr 2, s. 228-237Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. Methods Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)). Conclusions This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.

  • 59. Fridriksson, Jon
    et al.
    Gunseus, Katarina
    Stattin, Pär
    Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York City, USA.
    Information on pros and cons of prostate-specific antigen testing to men prior to blood draw: A study from the National Prostate Cancer Register (NPCR) of Sweden2012Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 5, s. 326-331Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Recent guidelines on serum testing of prostate-specific antigen (PSA) levels in asymptomatic men emphasize the importance of an informed decision. This study assessed the proportion of men who had received written or oral information on the possible consequences of testing of serum levels of PSA before blood draw.

    Material and methods. From the National Prostate Cancer Register (NPCR) in Sweden, 600 men per year were randomly selected out of all men with T1c prostate cancer who were diagnosed in the work-up of a PSA test as a part of health examination in 2006-2008. In a mailed questionnaire these men were asked whether and how they had been informed about the pros and cons of a PSA test prior to blood draw.

    Results. In total, 1621 out of 1800 men (90.1%) responded to the questionnaire; 39/1563 (2.5%) reported that they had received only written information before testing, 179/1563 (11.5%) had received both oral and written information, 763/1563 (48.8%) had received oral information only, 423/1563 (27.1%) had not received any information and 159/1563 (10.2%) were not aware of that a PSA test had been performed.

    Conclusions. The proportion of men who had received written information on the pros and cons of a PSA test before blood draw in the setting of a health examination was low. Improved routines for giving information to the patient before a PSA test are warranted.

  • 60.
    Fridriksson, Jon Örn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Folkvaljon, Yasin
    Lundström, Karl-Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Robinson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Ryhov Hospital, Jönköping, Sweden.
    Carlsson, Stefan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Long-term adverse effects after retropubic and robot-assisted radical prostatectomy: Nationwide, population-based study2017Ingår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 116, nr 4, s. 500-506Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objectives: Surgery for prostate cancer is associated with adverse effects. We studied long-term risk of adverse effects after retropubic (RRP) and robot-assisted radical prostatectomy (RARP).

    Methods: In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level.

    Results: A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42-0.63) and RR for procedures 0.46 (95%CI = 0.38-0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01-2.16), and RR for procedures 1.52 (95%CI = 1.02-2.26).

    Conclusions: The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.

  • 61. Fritz, Josef
    et al.
    Bjorge, Tone
    Nagel, Gabriele
    Concin, Hans
    Manjer, Jonas
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Uppsala universitet.
    Stattin, Pär
    Stocks, Tanja
    Ulmer, Hanno
    Insulin resistance measured by the triglyceride-glucose index and risk of obesity-related cancers: An epidemiological investigation in more than 500,000 individuals.2019Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 15, s. 1552-1552Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. We aimed to determine to what extent insulin resistance measured as the logarithmized triglyceride glucose product (TyG index) mediates the effect of BMI on risk of obesity-related cancers. Methods: A total of 510,471 individuals from six European cohorts with a mean age of 43.1 years were included in the study. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with ten common obesity-related cancer sites, and quantified the proportion of the effect of BMI mediated through TyG index. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney (hazard ratio (HR) per one standard deviation increase 1.13, 95% confidence interval: 1.07-1.20), liver (1.13, 1.04-1.23), pancreas (1.12, 1.06-1.19), colon (1.07, 1.03-1.10), and rectum (1.09, 1.04-1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%), and colon (20%); smaller proportions for kidney (15%) and liver (11%); none for endometrium, ovary and breast (postmenopausal). Conclusions: In this pooled cohort study including more than 500,000 individuals, insulin resistance measured as the logarithmized triglyceride glucose product significantly mediated the effect of overweight and obesity on risk of cancers of the kidney, liver, pancreas, colon, and rectum. In contrast, insulin resistance did not mediate the risk for cancers of the endometrium, ovary and breast. Our results confirm a promoting role of insulin resistance in the pathogenesis of gastrointestinal cancers. Although often claimed, insulin resistance does not appear to connect excess body weight with cancers of the female reproductive organs.

  • 62.
    Friðriksson, Jón Örn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Holmberg, Erik
    Adolfsson, Jan
    Lambe, Mats
    Bill-Axelson, Anna
    Carlsson, Stefan
    Hugosson, Jonas
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Rehospitalization after radical prostatectomy in a nationwide, population-based study2014Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 192, nr 1, s. 112-119Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To investigate readmission frequencies during the 90 days following radical prostatectomy and to assess readmission risk associated with potentially related variables.

    MATERIALS AND METHODS: Using the population-based, nationwide database Prostate Cancer data Base Sweden (PCBaSe), we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy (RP) as their primary treatment, and we used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load, and patient characteristics.

    RESULTS: During the 90 postoperative days, 2,317 (10%) of the 24,122 men identified were non-electively readmitted, specifically 10% after retropubic radical prostatectomy (RRP), 9% after robot-assisted RP (RALP) and 11% after laparoscopic RP (LRP). The range in the readmission frequency between hospitals was 0-35%. A higher risk of readmission was associated with early calendar period (2009-2011 vs. 2000-2002: odds ratio (OR), 0.71; 95% confidence interval (CI), 0.61-0.83), greater age (≥70 years vs. <60 years: OR, 1.17; 95% CI, 1.00-1.36), higher risk category (high vs. low-risk category: OR, 1.78; 95% CI, 1.57-2.03), high comorbidity (Charlson comorbidity index ≥3 vs. 0: OR, 1.77; 95% CI, 1.29-2.44), and low hospital surgical volume (≥150 vs. <30 RPs per year: OR, 0.70; 95% CI, 0.60-0.81).

    CONCLUSIONS: Readmission rates after different RP methods were similar, ranging from 9% to 11%, with a wide variation between hospitals. Readmission rates can be used as an indicator of perioperative care quality, but potential confounders need to be adjusted to avoid bias.

  • 63. Gnanapragasam, V. J.
    et al.
    Bratt, O.
    Muir, K.
    Lees, L. S.
    Huang, H. H.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Lophatananon, A.
    The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study2018Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikel-id 31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.

    Methods: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.

    Results: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n =3D 20,586), C-index 0.77 vs. 074; radiotherapy (n =3D 11,872), C-index 0.73 vs. 0.69; and conservative management (n =3D 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).

    Conclusions: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

  • 64. Gram, I T
    et al.
    Norat, T
    Rinaldi, S
    Dossus, L
    Lukanova, A
    Téhard, B
    Clavel-Chapelon, F
    van Gils, C H
    van Noord, P A H
    Peeters, P H M
    Bueno-de-Mesquita, H B
    Nagel, G
    Linseisen, J
    Lahmann, P H
    Boeing, H
    Palli, D
    Sacerdote, C
    Panico, S
    Tumino, R
    Sieri, S
    Dorronsoro, M
    Quirós, J R
    Navarro, C A
    Barricarte, A
    Tormo, M-J
    González, C A
    Overvad, K
    Paaske Johnsen, S
    Olsen, A
    Tjønneland, A
    Travis, R
    Allen, N
    Bingham, S
    Khaw, K-T
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Trichopoulou, A
    Kalapothaki, V
    Psaltopoulou, T
    Casagrande, C
    Riboli, E
    Kaaks, R
    Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.2006Ingår i: Int J Obes (Lond), ISSN 0307-0565, Vol. 30, nr 11, s. 1623-31Artikel i tidskrift (Refereegranskat)
  • 65. Grotta, Alessandra
    et al.
    Bottai, Matteo
    Adami, Hans-Olov
    Adams, Swann Arp
    Akre, Olof
    Blair, Steven Noel
    Mariosa, Daniela
    Nyrén, Olof
    Ye, Weimin
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bellocco, Rino
    Trolle Lagerros, Ylva
    Physical activity and body mass index as predictors of prostate cancer risk2015Ingår i: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 33, nr 10, s. 1495-1502Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Physical activity and body mass index (BMI) are involved in prostate cancer etiology; possible biologic mechanisms include their effects on hormonal levels. Our aim was to investigate the relationship between physical activity, obesity, and prostate cancer.

    METHODS: We followed a cohort of 13,109 Swedish men for 13 years and investigated the association of self-reported physical activity and BMI at baseline with prostate cancer incidence. We further analyzed whether BMI could modulate effects of physical activity. Occupational, recreational, and total physical activity were analyzed in relation to overall, localized, and advanced prostate cancer.

    RESULTS: During the study follow-up, we observed a total of 904 cases of prostate cancer (429 localized, 407 advanced, and 68 unclassified). High levels of occupational physical activity were associated with a nonsignificantly decreased risk of overall (HR 0.81, 95 % CI 0.61-1.07), localized (HR 0.75, 95 % CI 0.51-1.12), and advanced (HR 0.85, 95 % CI 0.55-1.31) prostate cancer. We found no association between high BMI and risk of prostate cancer incidence: We observed, however, a significant interaction between BMI and leisure physical activity.

    CONCLUSION: No association was confirmed between total physical activity and localized or advanced prostate cancer. The highest, relative to the lowest, level of occupational physical activity tended to be linked to a lower risk of prostate cancer, with a suggested dose-response relationship. We found no association between high BMI and risk of prostate cancer incidence; however, our analyses suggested an interaction between BMI and physical activity during recreational time that merits further investigation in future studies.

  • 66. Grundmark, B.
    et al.
    Garmo, H.
    Zethelius, B.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lambe, M.
    Holmberg, L.
    Anti-androgen prescribing patterns, patient treatment adherence and influencing factors; results from the nationwide PCBaSe Sweden2012Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 68, nr 12, s. 1619-1630Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment. A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose. First line monotherapy AA was planned in 4.4 % of all incident cases and in 2.1 % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79 %) received the approved daily dose of 150 mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75 years and disease categorised as low risk was noted in 297 men (21 %). Sixty percent of the men adhered well, i.e. to a parts per thousand yen80 %. Age above 75 years and less severe disease were both negatively associated with adherence. Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.

  • 67. Gu, Fangyi
    et al.
    Schumacher, Fredrick R
    Canzian, Federico
    Allen, Naomi E
    Albanes, Demetrius
    Berg, Christine D
    Berndt, Sonja I
    Boeing, Heiner
    Bueno-de-Mesquita, H Bas
    Buring, Julie E
    Chabbert-Buffet, Nathalie
    Chanock, Stephen J
    Clavel-Chapelon, Françoise
    Dumeaux, Vanessa
    Gaziano, J Michael
    Giovannucci, Edward L
    Haiman, Christopher A
    Hankinson, Susan E
    Hayes, Richard B
    Henderson, Brian E
    Hunter, David J
    Hoover, Robert N
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. International Agency for Research on Cancer (IARC), Lyon, France.
    Key, Timothy J
    Khaw, Kay-Tee
    Kolonel, Laurence N
    Lagiou, Pagona
    Lee, I-Min
    LeMarchand, Loic
    Lund, Eiliv
    Ma, Jing
    Onland-Moret, N Charlotte
    Overvad, Kim
    Rodriguez, Laudina
    Sacerdote, Carlotta
    Sánchez, Maria-José
    Stampfer, Meir J
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stram, Daniel O
    Thomas, Gilles
    Thun, Michael J
    Tjønneland, Anne
    Trichopoulos, Dimitrios
    Tumino, Rosario
    Virtamo, Jarmo
    Weinstein, Stephanie J
    Willett, Walter C
    Yeager, Meredith
    Zhang, Shumin M
    Kaaks, Rudolf
    Riboli, Elio
    Ziegler, Regina G
    Kraft, Peter
    Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer2010Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, nr 11, s. 2877-2887Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins.

    Methods: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in >5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium.

    Results: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P < 2.1 × 10−4); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R2 = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers.

    Conclusion: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women.

    Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.

  • 68. Gudmundsson, Julius
    et al.
    Sulem, Patrick
    Rafnar, Thorunn
    Bergthorsson, Jon T
    Manolescu, Andrei
    Gudbjartsson, Daniel
    Agnarsson, Bjarni A
    Sigurdsson, Asgeir
    Benediktsdottir, Kristrun R
    Blondal, Thorarinn
    Jakobsdottir, Margret
    Stacey, Simon N
    Kostic, Jelena
    Kristinsson, Kari T
    Birgisdottir, Birgitta
    Ghosh, Shyamali
    Magnusdottir, Droplaug N
    Thorlacius, Steinunn
    Thorleifsson, Gudmar
    Zheng, S Lilly
    Sun, Jielin
    Chang, Bao-Li
    Elmore, J Bradford
    Breyer, Joan P
    McReynolds, Kate M
    Bradley, Kevin M
    Yaspan, Brian L
    Wiklund, Fredrik
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lindström, Sara
    Adami, Hans-Olov
    McDonnell, Shannon K
    Schaid, Daniel J
    Cunningham, Julie M
    Wang, Liang
    Cerhan, James R
    St Sauver, Jennifer L
    Isaacs, Sara D
    Wiley, Kathleen E
    Partin, Alan W
    Walsh, Patrick C
    Polo, Sonia
    Ruiz-Echarri, Manuel
    Navarrete, Sebastian
    Fuertes, Fernando
    Saez, Berta
    Godino, Javier
    Weijerman, Philip C
    Swinkels, Dorine W
    Aben, Katja K
    Witjes, J Alfred
    Suarez, Brian K
    Helfand, Brian T
    Frigge, Michael L
    Kristjansson, Kristleifur
    Ober, Carole
    Jonsson, Eirikur
    Einarsson, Gudmundur V
    Xu, Jianfeng
    Gronberg, Henrik
    Smith, Jeffrey R
    Thibodeau, Stephen N
    Isaacs, William B
    Catalona, William J
    Mayordomo, Jose I
    Kiemeney, Lambertus A
    Barkardottir, Rosa B
    Gulcher, Jeffrey R
    Thorsteinsdottir, Unnur
    Kong, Augustine
    Stefansson, Kari
    Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer.2008Ingår i: Nat Genet, ISSN 1546-1718, Vol. 40, nr 3, s. 281-3Artikel i tidskrift (Refereegranskat)
  • 69.
    Hagel, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Garmo, Hans
    Bill-Axelson, Anna
    Bratt, Ola
    Johansson, Jan-Erik
    Adolfsson, Jan
    Lambe, Mats
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    PCBaSe Sweden: a register-based resource for prostate cancer research2009Ingår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, nr 5, s. 342-349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden.

  • 70.
    Halin Bergström, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nilsson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adamo, Hanibal
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Thysell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jernberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 6, artikel-id e0157280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RTPCR showed that the main site of HO-1 synthesis was HO-1(+) macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1(+) macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1(+) macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1(+) macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1(+) macrophages may have an important role in prostate cancer.

  • 71.
    Halin, Sofia
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Rudolfsson, Stina
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Doll, Jennifer A
    Crawford, Susan E
    Bergh, Anders
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Decreased pigment epithelium-derived factor is associated with metastatic phenotype in human and rat prostate tumors.2004Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 64, nr 16, s. 5664-71Artikel i tidskrift (Refereegranskat)
  • 72.
    Hammarsten, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Cipriano, Mariateresa
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Josefsson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Egevad, Lars
    Granfors, Torvald
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Phospho-Akt Immunoreactivity in Prostate Cancer: Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 10, s. e47994-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms. Methodology/Principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8-10, but not for patients with Gleason score 6-7. Conclusions/Significance: Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6-7.

  • 73.
    Hammarsten, Peter
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Karalija, Amar
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Josefsson, Andreas
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Rudolfsson, Stina Häggström
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Wikström, Pernilla
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Egevad, Lars
    Granfors, Torvald
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bergh, Anders
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.2010Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 16, nr 4, s. 1245-1255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients. EXPERIMENTAL DESIGN: We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR. The staining pattern was scored and related to clinicopathologic parameters and to outcome. RESULTS: Low phosphorylation of EGFR in prostate epithelial cells, both in the tumor and surprisingly also in the surrounding nonmalignant tissue, was associated with significantly longer cancer-specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR immunoreactivity was significantly correlated to tumor cell proliferation, tumor vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients with metastases had significantly higher immunoreactivity for tumor and nonmalignant epithelial pEGFR compared with patients without metastases. CONCLUSIONS: Low pEGFR immunoreactivity is associated with the favorable prognosis in prostate cancer patients and may provide information about which patients with Gleason score 6 and 7 tumors that will survive their disease even without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors give prognostic information.

  • 74.
    Hammarsten, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Scherdin, Tove Dahl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hagglöf, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersson, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Granfors, Torvald
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    High Caveolin-1 Expression in Tumor Stroma Is Associated with a Favourable Outcome in Prostate Cancer Patients Managed by Watchful Waiting2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 10, artikel-id e0164016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the present study we have investigated whether Caveolin-1 expression in non-malignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients managed by watchful waiting. Caveolin-1 was measured in prostate tissues obtained through transurethral resection of the prostate from 395 patients diagnosed with prostate cancer. The majority of the patients (n = 298) were followed by watchful waiting after diagnosis. Tissue microarrays constructed from malignant and non-malignant prostate tissue were stained with an antibody against Caveolin-1. The staining pattern was scored and related to clinicopathologic parameters and outcome. Microdissection and qRT-PCR analysis of Cav-1 was done of the prostate stroma from non-malignant tissue and stroma from Gleason 3 and 4 tumors. Cav-1 RNA expression was highest in non-malignant tissue and decreased during cancer progression. High expression of Caveolin-1 in tumor stroma was associated with significantly longer cancer specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were combined with Caveolin-1 in a Cox regression model. High stromal Caveolin-1 immunoreactivity in prostate tumors is associated with a favourable prognosis in prostate cancer patients managed by watchful waiting. Caveolin-1 could possibly become a useful prognostic marker for prostate cancer patients that are potential candidates for active surveillance.

  • 75. Hedlund, Per Olov
    et al.
    Damber, Jan-Erik
    Hagerman, Inger
    Haukaas, Svein
    Henriksson, Peter
    Iversen, Peter
    Johansson, Robert
    Klarskov, Peter
    Lundbeck, Finn
    Rasmussen, Finn
    Varenhorst, Eberhard
    Viitanen, Jouko
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.2008Ingår i: Scand J Urol Nephrol, ISSN 0036-5599, Vol. 42, nr 3, s. 220-9Artikel i tidskrift (Refereegranskat)
  • 76. Holl, Katsiaryna
    et al.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Surcel, Heljä-Marja
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Koskela, Pentti
    Dillner, Joakim
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Olafsdottir, Gudridur H
    Ogmundsdottir, Helga M
    Pukkala, Eero
    Lehtinen, Matti
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lukanova, Annekatrin
    Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case-referent study.2009Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, nr 12, s. 2923-2928Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. (c) 2009 UICC.

  • 77. Holl, Katsiaryna
    et al.
    Surcel, Helja-Marja
    Koskela, Pentti
    Dillner, Joakim
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Kaasila, Marjo
    Olafsdottir, Gudridur H
    Ogmundsdottir, Helga M
    Pukkala, Eero
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lehtinen, Matti
    Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study2008Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, nr 9, s. 816-822Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers, and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR), 2.50; 95% confidence interval (CI), 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73; 950% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age (OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.

  • 78.
    Holmström, Benny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Holmberg, Erik
    Egevad, Lars
    Adolfsson, Jan
    Johansson, Jan-Erik
    Hugosson, Jonas
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Outcome of primary versus deferred radical prostatectomy in the National Prostate Cancer Register of Sweden follow-up study2010Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, nr 4, s. 1322-1327Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose We assessed outcomes in terms of adverse pathology and prostate cancer specific mortality in men who underwent primary or deferred radical prostatectomy.

    Materials and Methods In the National Prostate Cancer Register of Sweden Follow-Up Study men 70 years old or younger at diagnosis with localized low to intermediate risk prostate cancer diagnosed from 1997 to 2002 were identified. Outcome in terms of adverse pathology, namely upgrading of Gleason score, positive surgical margins and extraprostatic extension, as well as prostate cancer specific mortality, was assessed in 2,344 men who underwent primary radical prostatectomy and 222 who underwent deferred radical prostatectomy after an initial period of surveillance.

    Results Upgrading of Gleason score in surgical specimens vs core biopsies was less frequent after primary (25%) vs deferred radical prostatectomy (38%), p <0.001. There was no significant difference in the percentage of men who underwent primary vs deferred radical prostatectomy for positive surgical margins (33% vs 24%) or extraprostatic extension (27% vs 25%), and there was no difference in any 1 or more of the 3 adverse pathology features (55% vs 56%). After a median followup of 8 years 0.7% of men in the primary radical prostatectomy group and 0.9% in the deferred radical prostatectomy group had died of prostate cancer.

    Conclusions There was no significant difference in the presence of any 1 or more adverse pathology features or in prostate cancer specific mortality after primary compared to deferred radical prostatectomy. However, longer followup is needed to conclusively evaluate the role of deferred radical prostatectomy.

  • 79.
    Holmström, Benny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. International Agency for Research on Cancer (IARC), Lyon, France.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stenman, Ulf-Håkan
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Prostate specific antigen for early detection of prostate cancer: longitudinal study2009Ingår i: BMJ (Clinical research ed.), ISSN 1468-5833, Vol. 339, s. b3537-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate cancer screening trial results.

    DESIGN: Case-control study nested in longitudinal cohort.

    SETTING: Västerbotten Intervention Project cohort, Umeå, Sweden.

    PARTICIPANTS: 540 cases and 1034 controls matched for age and date of blood draw.

    MAIN OUTCOME MEASURE: Validity of prostate specific antigen for prediction of subsequent prostate cancer diagnosis by record linkage to cancer registry.

    RESULTS: Blood samples were drawn on average 7.1 (SD 3.7) years before diagnosis. The area under the curve for prostate specific antigen was 0.84 (95% confidence interval 0.82 to 0.86). At prostate specific antigen cut-off values of 3, 4, and 5 ng/ml, sensitivity estimates were 59%, 44%, and 33%, and specificity estimates were 87%, 92%, and 95%. The positive likelihood ratio commonly considered to "rule in disease" is 10; in this study the positive likelihood ratios were 4.5, 5.5, and 6.4 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. The negative likelihood ratio commonly considered to "rule out disease" is 0.1; in this study the negative likelihood ratios were 0.47, 0.61, and 0.70 for prostate specific antigen cut-off values of 3, 4, and 5 ng/ml. For a cut-off of 1.0 ng/ml, the negative likelihood ratio was 0.08.

    CONCLUSIONS: No single cut-off value for prostate specific antigen concentration attained likelihood ratios formally required for a screening test. Prostate specific antigen concentrations below 1.0 ng/ml virtually ruled out a prostate cancer diagnosis during the follow-up. Additional biomarkers for early detection of prostate cancer are needed before population based screening for prostate cancer should be introduced.

  • 80.
    Holmström, Benny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Johansson, Mattias
    International Agency for Research on Cancer (IARC), Lyon, France.
    Bratt, Ola
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    PSA-testet håller inte för screening: bra – men inte tillräckligt bra2009Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 7, s. 436, 438-439Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Prostatacancer är den vanligaste cancersjukdomen och den vanligaste cancerrelaterade dödsorsaken bland män i Sverige. Screening för prostataspecifikt antigen (PSA) minskade dödligheten i prostatacancer med 20 procent i en stor randomiserad studie. En utvärdering av PSA-test med sannolikhetskvot (likelihood ratio) visade att det inte uppfyller kriterierna för ett screeningtest. Män ska ha information om PSA-testets för- och nackdelar innan testet utförs. En broschyr med sådan information finns tillgänglig på <http://www.socialstyrelsen.se/publikationer2007/2007-114-90>.

  • 81. Hsu, Fang-Chi
    et al.
    Lindström, Sara
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Sun, Jielin
    Wiklund, Fredrik
    Chen, Shyh-Huei
    Adami, Hans-Olov
    Turner, Aubrey R
    Liu, Wennuan
    Bälter, Katarina
    Kim, Jin Woo
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Chang, Bao-Li
    Isaacs, William B
    Xu, Jianfeng
    Grönberg, Henrik
    Zheng, S Lilly
    A multigenic approach to evaluating prostate cancer risk in a systematic replication study.2008Ingår i: Cancer Genet Cytogenet, ISSN 1873-4456, Vol. 183, nr 2, s. 94-8Artikel i tidskrift (Refereegranskat)
  • 82. Hsu, Fang-Chi
    et al.
    Sun, Jielin
    Wiklund, Fredrik
    Isaacs, Sarah D
    Wiley, Kathleen E
    Purcell, Lina D
    Gao, Zhengrong
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Zhu, Yi
    Kim, Seong-Tae
    Zhang, Zheng
    Liu, Wennuan
    Chang, Bao-Li
    Walsh, Patrick C
    Duggan, David
    Carpten, John D
    Isaacs, William B
    Grönberg, Henrik
    Xu, Jianfeng
    Zheng, S Lilly
    A novel prostate cancer susceptibility locus at 19q13.2009Ingår i: Cancer research, ISSN 1538-7445, Vol. 69, nr 7, s. 2720-3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden [Cancer of the Prostate in Sweden (CAPS)]. Two of these 22 SNPs were significantly associated with PCa risk (P<0.05). We then genotyped these two SNPs in the remaining cases (n=2,393) and controls (n=1,222) from CAPS and found that rs887391 at 19q13 was highly associated with PCa risk (P=9.4 x 10(-4)). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital (JHH), albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P=3.2 x 10(-7) from a combined allelic test. A fine-mapping study in a 110-kb region at 19q13 among CAPS and JHH study populations revealed that rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted.

  • 83.
    Hultdin, Johan
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Näringsforskning.
    Stattin, Pär
    Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study.2005Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 113, nr 5, s. 819-824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of folate metabolism in cancer development is a topic of much current interest, with maintenance of adequate folate status tending to show a protective effect. Aberrant methylation, primarily hypermethylation of certain genes including tumor suppressors, has been implicated in prostate cancer development. Folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation. We related plasma levels of these factors to prostate cancer risk in a prospective study of 254 case subjects and 514 matched control subjects. Increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk, with an odds ratio of 1.60 (95% CI = 1.03-2.49; p(trend) = 0.02) for folate and 2.63 (95% CI = 1.61-4.29; p(trend) < 0.001) for vitamin B12 for highest vs. lowest quartile. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance (OR = 0.67; 95% CI = 0.43-1.04; p(trend) = 0.08). After adjustment for the other 2 plasma variables, body mass index and smoking, a statistically significant increased risk remained only for vitamin B12 (OR = 2.96; 95% CI = 1.58-5.55; p(trend) = 0.001). Adjusted OR for folate and homocysteine were 1.30 (95% CI = 0.74-2.24; p(trend) = 0.17) and 0.91 (95% CI = 0.51-1.58; p(trend) = 0.60), respectively. Our results suggest that factors contributing to folate status are not protective against prostate cancer. On the contrary, vitamin B12, associated with an up to 3-fold increase in risk, and possibly also folate, may even stimulate prostate cancer development. These findings are novel and should be explored further in future studies. (c) 2004 Wiley-Liss, Inc.

  • 84. Hunt, Kelly J
    et al.
    Lukanova, Annekatrin
    Rinaldi, Sabina
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Norat, Teresa
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Riboli, Elio
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Kaaks, Rudolf
    A potential inverse association between insulin-like growth factor I and hypertension in a cross-sectional study.2006Ingår i: Annals of Epidemiology, ISSN 1047-2797, E-ISSN 1873-2585, Vol. 16, nr 7, s. 563-571Artikel i tidskrift (Refereegranskat)
  • 85.
    Hägglöf, Christina
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Josefsson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Paulsson, Janna
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Östman, Arne
    Stromal PDGFRbeta expression in prostate tumors and non-malignant prostate tissue predicts prostate cancer survival2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 5, s. e10747-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The study revealed a number of novel associations between stromal PDGFRbeta expression in prostate tumors and several important clinical characteristics, including survival.

  • 86.
    Hägglöf, Christina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Strömvall, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Egevad, Lars
    Josefsson, Andreas
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Granfors, Torvald
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    TMPRSS2-ERG Expression Predicts Prostate Cancer Survival and Associates with Stromal Biomarkers2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 2, s. e86824-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFR beta and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.

  • 87.
    Häggstrom, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Ulmert, David
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Ulmer, Hanno
    nnsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Manjer, Jonas
    Lund Univ, Dept Plast Surg, Skåne Univ Hosp, Malmö, Sweden.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
    Almqvist, Martin
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Austria.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Prospective study on metabolic factors and risk of prostate cancer2012Ingår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 118, nr 24, s. 6199-6206Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer.

    METHODS: In the Metabolic Syndrome and Cancer Project (Me-Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement.

    RESULTS: During a mean follow-up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62-1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74-1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08-1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07-2.45); and per 1-unit increase of the composite z score: RR, 1.13 (95% CI, 1.03-1.25).

    CONCLUSIONS: The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer. 

  • 88.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Rapp, Kilian
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Manjer, Jonas
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Ulmer, Hanno
    Med Univ Innsbruck, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Almqvist, Martin
    Lund Univ, Skåne Univ Hosp, Dept Surg, Malmö, Sweden.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Australia.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Nagel, Gabriele
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Metabolic factors associated with risk of renal cell carcinoma2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, s. e57475-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.

  • 89.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Clinical Sciences, Diabetes and Cardiovascular Diseases, Genetic Epidemiology, Lund University, Lund, Sweden.
    Garmo, Hans
    Holmberg, Lars
    Van Hemelrijck, Mieke
    Interpretation of conventional survival analysis and competing-risk analysis: an example of hypertension and prostate cancer2016Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, nr 6, s. 850-852Artikel i tidskrift (Refereegranskat)
  • 90.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Nagel, Gabriele
    Manjer, Jonas
    Bjørge, Tone
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Engeland, Anders
    Ulmer, Hanno
    Lindkvist, Bjorn
    Selmer, Randi
    Concin, Hans
    Tretli, Steinar
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations2014Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, nr 6, s. 823-828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

    Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score.

    Results: During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%.

    Conclusions: In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

  • 91.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Nagel, Gabriele
    Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
    Manjer, Jonas
    Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
    Bjørge, Tone
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Engeland, Anders
    Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
    Ulmer, Hanno
    Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
    Lindkvist, Björn
    Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
    Selmer, Randi
    Norwegian Institute of Public Health, Oslo, Norway.
    Concin, Hans
    Agency for Preventive and Social Medicine, Bregenz, Austria.
    Tretli, Steinar
    Institute of Population-based Cancer Research, The Cancer Registry of Norway, Oslo, Norway.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Competing risk analysis of metabolic factors and prostate cancerManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: Men at risk of prostate cancer are also at risk of competing events but this has been ignored in most studies of metabolic aberrations and prostate cancer. The aim of this study was to assess probabilities of prostate cancer and prostate cancer death by use of competing risk analysis.

    Methods: In the Metabolic syndrome and Cancer project (Me-Can), data on body mass index, blood pressure, glucose, total cholesterol, and triglycerides were collected from 285 040 men. Probabilities of prostate cancer, prostate cancer death and competing events, i.e. all-cause death or death from other causes, respectively, were calculated for men with normal (bottom 84%) and high (top 16%) levels of each metabolic factor and a composite score based on all metabolic factors

    Results: During follow up, 5893 men were diagnosed with prostate cancer, 1013 men died of prostate cancer, and 26 328 men died of other causes. Men with high levels of metabolic factors had decreased probability of prostate cancer, similar probability of prostate cancer death, and increased probability of other causes of death compared to men with normal levels. After 1996, when prostate specific antigen was used for detection of prostate cancer, men up to 80 years with normal levels of metabolic factors had 13% probability of prostate cancer and 37% probability of death from all causes. For men with high levels of metabolic factors, corresponding probabilities were 12% and 47%.

    Conclusions: Men with metabolic aberrations had a decreased probability of prostate cancer but a substantially higher probability of death from all causes.

  • 92.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. null.
    Rapp, Kilian
    Univ Ulm, Inst Epidemiol, Ulm, Germany.
    Bjørge, Tone
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Lindkvist, Björn
    Univ Gothenburg, Sahlgrenska Acad, Dept Med, Gothenburg, Sweden.
    Concin, Hans
    Agcy Prevent & Social Med, Bregenz, Austria.
    Engeland, Anders
    Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
    Manjer, Jonas
    Malmö Univ Hosp, Dept Surg, Malmö, Sweden.
    Ulmer, Hanno
    Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Tretli, Steinar
    Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. null.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. null.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. null.
    Metabolic syndrome and risk of bladder cancer: prospective cohort study in the metabolic syndrome and cancer project (Me-Can)2011Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, nr 8, s. 1890-1898Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There are little data on the putative association between factors in the metabolic syndrome (MetS) and risk of bladder cancer. In the Metabolic Syndrome and Cancer project (Me-Can), measurements of height, weight, blood pressure and circulating levels of glucose, cholesterol, and triglycerides had been collected from 578,700 subjects in cohorts in Norway, Austria, and Sweden. We used Cox proportional hazard models to calculate relative risks (RRs) of bladder cancer by exposures divided into quintiles, in categories according to the World Health Organisation (WHO) and as a continuous standardized variable (z-score with mean = 0 and standard deviation = 1) for each separate component and its standardized sum, a composite MetS score. RRs were corrected for random error in measurements. During a mean follow-up of 11.7 years (SD = 7.6), 1,587 men and 327 women were diagnosed with bladder cancer. Significant associations with risk were found among men per one unit increment of z-score for blood pressure, RR = 1.13 (95% CI 1.03-1.25), and the composite MetS score, RR = 1.10 (95% CI 1.01-1.18). Among women, glucose was nonsignificantly associated with risk, RR = 1.41 (95% CI 0.97-2.06). No statistically significant interactions were found between the components in the MetS in relation to bladder cancer risk. Hypertension and a composite MetS score were significantly but modestly associated with an increased risk of bladder cancer among men and elevated glucose was associated with a nonsignificant increase in risk among women.

  • 93.
    Häggström, Christel
    et al.
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Van Hemelrijck, Mieke
    Zethelius, Björn
    Robinson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Grundmark, Birgitta
    Holmberg, Lars
    Gudbjörnsdottir, Soffia
    Garmo, Hans
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer2017Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, nr 3, s. 611-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.

  • 94.
    Hörnberg, Emma
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bovinder Ylitalo, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Crnalic, Sead
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 4, s. e19059-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Constitutively active androgen receptor variants (AR-V) lacking the ligand binding domain (LBD) may promote  the development of castration-resistant prostate cancer (CRPC). The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN) and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival.

    Methodology/Principal Findings: Hormone-naı¨ve (n = 10) and CRPC bone metastases samples (n = 30) were obtained from  40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl) and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival.

    Conclusions/Significance: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis.

  • 95. Iglesias-Gato, Diego
    et al.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Tyanova, Stefka
    Lavallee, Charlotte
    Thysell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Carlsson, Jessica
    Hägglöf, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Cox, Juergen
    Andren, Ove
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Egevad, Lars
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bjartell, Anders
    Collins, Colin C.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Geiger, Tamar
    Mann, Matthias
    Flores-Morales, Amilcar
    The Proteome of Primary Prostate Cancer2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 5, s. 942-952Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries. Objectives: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness. Design, setting, and participants: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two independent cohorts of PCa patients (summing 752 cases) managed by expectancy were used for immunohistochemical evaluation of proneuropeptide-Y (pro-NPY) as a prognostic biomarker. Results and limitations: Over 9000 proteins were identified as expressed in the human prostate. Tumor tissue exhibited elevated expression of proteins involved in multiple anabolic processes including fatty acid and protein synthesis, ribosomal biogenesis and protein secretion but no overt evidence of increased proliferation was observed. Tumors also showed increased levels of mitochondrial proteins, which was associated with elevated oxidative phosphorylation capacity measured in situ. Molecular analysis indicated that some of the proteins overexpressed in tumors, such as carnitine palmitoyltransferase 2 (CPT2, fatty acid transporter), coatomer protein complex, subunit alpha (COPA, vesicle secretion), and mitogen-and stress-activated protein kinase 1 and 2 (MSK1/2, protein kinase) regulate the proliferation of PCa cells. Additionally, pro-NPY was found overexpressed in PCa (5-fold, p < 0.05), but largely absent in other solid tumor types. Pro-NPY expression, alone or in combination with the ERG status of the tumor, was associated with an increased risk of PCa specific mortality, especially in patients with Gleason score <= 7 tumors. Conclusions: This study represents the first system-wide quantitative analysis of proteome changes associated to localized prostate cancer and as such constitutes a valuable resource for understanding the complex metabolic changes occurring in this disease. We also demonstrated that pro-NPY, a protein that showed differential expression between high and low risk tumors in our proteomic analysis, is also a PCa specific prognostic biomarker associated with increased risk for disease specific death in patients carrying low risk tumors. Patient summary: The identification of proteins whose expression change in prostate cancer provides novel mechanistic information related to the disease etiology. We hope that future studies will prove the value of this proteome dataset for development of novel therapies and biomarkers. 

  • 96. Jakszyn, Paula G
    et al.
    Allen, Naomi E
    Lujan-Barroso, Leila
    Gonzalez, Carlos A
    Key, Timothy J
    Fonseca-Nunes, Ana
    Tjønneland, Anne
    Føns-Johnsen, Nina
    Overvad, Kim
    Teucher, Birgit
    Li, Kuanrong
    Boeing, Heiner
    Trichopoulou, Antonia
    Oikonomou, Eleni
    Sarantopoulou, Maria
    Saieva, Calogero
    Krogh, Vittorio
    Tumino, Rosario
    Ricceri, Fulvio
    Bueno-de-Mesquita, H Bas
    Huerta, José M
    Ardanaz, Eva
    Arguelles, Marcial V
    Molina-Montes, Esther
    Larrañaga, Nerea
    Wirfält, Elisabet
    Wallström, Peter
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York.
    Khaw, Kay-Tee
    Jenab, Mazda
    Fedirko, Veronika
    Riboli, Elio
    Nitrosamines and Heme Iron and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition.2012Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, nr 3, s. 547-551Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The evidence about nitrosamines and heme iron intake and cancer risk is limited, despite the biologic plausibility of the hypothesis that these factors might increase cancer risk. We investigated the association between dietary nitrosamines and heme iron and the risk of prostate cancer among participants of European Prospective Investigation into Cancer and Nutrition (EPIC).METHODS: Data on food consumption and complete follow-up for cancer occurrence was available for 139,005 men, recruited in 8 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, and study center, and adjusted for total energy intake, smoking status, marital status, dairy products, educational level, and body mass index.RESULTS: After a mean follow-up of 10 years, 4,606 participants were diagnosed with first incident prostate cancer. There was no overall association between prostate cancer risk and nitrosamines exposure (preformed and endogenous) or heme iron intake (HR for a doubling of intake: 1.00; 95% CI: 0.98-1.03 for N-Nitrosodimethlyamine, 0.95; 95% CI: 0.88-1.03 for endogenous Nitrosocompounds, and 1.00; 95 CI: 0.97-1.03 for heme iron).Conclusions and Impact: Our findings do not support an effect of nitrosamines (endogenous and exogenous) and heme iron intake on prostate cancer risk.

  • 97. Jan, Michael
    et al.
    Bonn, Stephanie E.
    Sjölander, Arvid
    Wiklund, Fredrik
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Holmberg, Erik
    Grönberg, Henrik
    Bälter, Katarina
    The roles of stress and social support in prostate cancer mortality2016Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 1, s. 47-55Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: This study aimed to evaluate the association between perceived stress, social support, disease progression and mortality in a nationwide population-based cohort of men with prostate cancer. Materials and methods: The study surveyed 4105 Swedish men treated for clinically localized prostate cancer regarding stress, grief, sleep habits and social support. Associations between these factors and mortality were assessed using multivariate Cox regression analysis. Results: Men with the highest levels of perceived stress had a statistically significantly increased rate of prostate cancer-specific mortality compared with men with low stress levels (hazard ratio 1.66, 95% confidence interval 1.05-2.63). Men with high stress levels also had a high frequency of grieving and sleep loss. They also had fewer people with whom to share their emotional problems and felt an inability to share most of their problems with partners, friends and family. Conclusions: This study contributes to the growing field of psychosocial quality of life research in men with prostate cancer. The findings show a significant association between prostate cancer-specific mortality and perceived stress in patients initially diagnosed with localized, non-metastatic prostate cancer. Significant associations between perceived stress and various psychosocial factors were also seen. The findings of this study could prove useful to target interventions to improve quality of life in men with prostate cancer.

  • 98. Jansson, K. Fredrik
    et al.
    Akre, Olof
    Garmo, Hans
    Bill-Axelson, Anna
    Adolfsson, Jan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bratt, Ola
    Concordance of tumor differentiation among brothers with Prostate Cancer2012Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, nr 4, s. 656-661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known. Objective: We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case. Design, setting and participants: We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer. Outcome measurements and statistical analysis: The relative risk of Gleason score-specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution. Results and limitations: Among brothers of index cases with Gleason score 8-10 cancer, the SIR was 2.53 (95% CI, 1.97-3.21) for a Gleason score 2-6 cancer and 4.00 (95% CI, 2.63-5.82) for a Gleason score 8-10 cancer. SIR for Gleason score 2-6 cancer among brothers decreased with time since the date of the index cases' diagnoses, whereas the risk of Gleason 8-10 cancer increased over time for brothers of index cases with Gleason 8-10 cancer (p for trend = 0.009). Conclusions: Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

  • 99. Johansen, Dorthe
    et al.
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lindkvist, Björn
    Björge, Tone
    Concin, Hans
    Almquist, Martin
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Engeland, Anders
    Ulmer, Hanno
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Selmer, Randi
    Nagel, Gabriele
    Tretli, Steinar
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Manjer, Jonas
    Metabolic factors and the risk of pancreatic cancer: a prospective analysis of almost 580,000 men and women in the Metabolic Syndrome and Cancer Project2010Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, nr 9, s. 2307-2317Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate the association between factors in metabolic syndrome (MetS; single and combined) and the risk of pancreatic cancer. METHODS: The Metabolic Syndrome and Cancer Project is a pooled cohort containing data on body mass index, blood pressure, and blood levels of glucose, cholesterol, and triglycerides. During follow-up, 862 individuals were diagnosed with pancreatic cancer. Cox proportional hazards analysis was used to calculate relative risks (RR) with 95% confidence intervals using the above-mentioned factors categorized into quintiles and transformed into z-scores. All z-scores were summarized and a second z-transformation creating a composite z-score for MetS was done. All risk estimates were calibrated to correct for a regression dilution bias. RESULTS: The trend over quintiles was positively associated with the risk of pancreatic cancer for mid-blood pressure (mid-BP) and glucose in men and for body mass index, mid-BP, and glucose in women. The z-score for the adjusted mid-BP (RR, 1.10; 1.01-1.20) and the calibrated z-score for glucose (RR, 1.37; 1.14-1.34) were positively associated with pancreatic cancer in men. In women, a positive association was found for calibrated z-scores for mid-BP (RR, 1.34; 1.08-1.66), for the calibrated z-score for glucose (RR, 1.98; 1.41-2.76), and for the composite z-score for MetS (RR, 1.58; 1.34-1.87). CONCLUSION: Our study adds further evidence to a possible link between abnormal glucose metabolism and risk of pancreatic cancer. IMPACT: To our knowledge, this is the first study on MetS and pancreatic cancer using prediagnostic measurements of the examined factors.

  • 100.
    Johansson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rudolfsson, Stina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Hammarsten, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Halin, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Pietras, Kristian
    Jones, Jonathan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Egevad, Lars
    Granfors, Torvald
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy2010Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 177, nr 2, s. 1031-1041Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mast cells affect growth in various human tumors, but their role in prostate cancer (PC) is unclear. Here, we identify mast cells as independent prognostic markers in PC using a large cohort of untreated PC patients with a long follow-up. By analyzing mast cells in different tissue compartments, our data indicate that intratumoral and peritumoral mast cells have anti- opposed to protumor properties. Intratumoral mast cells negatively regulate angiogenesis and tumor growth, whereas peritumoral mast cells stimulate the expansion of human prostate tumors. We also observed mast cell recruitment particularly to the peritumoral compartment in men during the formation of castrate-resistant prostate tumors. In our ortothopic rat model, mast cells accumulated in the peritumoral tissue where they enhanced angiogenesis and tumor growth. In line with this, prostate mast cells expressed high levels of the angiogenic factor FGF-2. Similar to the situation in men, mast cells infiltrated rat prostate tumors that relapsed after initially effective castration treatment, concurrent with a second wave of angiogenesis and an up-regulation of FGF-2. We conclude that mast cells are novel independent prognostic markers in PC and affect tumor progression in animals and patients. In addition, peritumoral mast cells provide FGF-2 to the tumor micro environment, which may contribute to their stimulating effect on angiogenesis.

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