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Stattin, Pär
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Crawley, D., Garmo, H., Rudman, S., Stattin, P., Zethelius, B., Holmberg, L., . . . Van Hemelrijck, M. (2018). Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer. BJU International, 121(2), 209-216
Open this publication in new window or tab >>Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer
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2018 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, no 2, p. 209-216Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

Subjects and Methods: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate-(T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

Results: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

Conclusions: Men with T2DM were less likely to receive curative treatment for localized intermediate-and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under-nor overtreated.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
diabetes, curative treatment, prostatectomy, external beam radiotherapy, #ProstateCancer, #PCSM
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-144946 (URN)10.1111/bju.13880 (DOI)000424029800012 ()28418195 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-06-09Bibliographically approved
FitzGerald, L. M., Zhao, S., Leonardson, A., Geybels, M. S., Kolb, S., Lin, D. W., . . . Stanford, J. L. (2018). Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases. Prostate Cancer and Prostatic Diseases, 21(2), 228-237
Open this publication in new window or tab >>Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases
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2018 (English)In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 21, no 2, p. 228-237Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-150859 (URN)10.1038/s41391-017-0029-2 (DOI)000437334500010 ()29298992 (PubMedID)2-s2.0-85040017696 (Scopus ID)
Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2018-09-07Bibliographically approved
Van Hemelrijck, M., Ulmer, H., Nagel, G., Peter, R. S., Fritz, J., Myte, R., . . . Stocks, T. (2018). Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria. PLoS ONE, 13(6), Article ID e0197830.
Open this publication in new window or tab >>Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0197830Article in journal (Refereed) Published
Abstract [en]

Background: Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail. Methods: Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10 +/- 2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years. Results: Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m(2) higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%Cl:0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%Cl: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m(2) higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups. Conclusion: BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases.

Place, publisher, year, edition, pages
Public Library Science, 2018
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-150785 (URN)10.1371/journal.pone.0197830 (DOI)000435090700031 ()29897925 (PubMedID)
Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2018-08-20Bibliographically approved
Ventimiglia, E., Folkvaljon, Y., Carlsson, S., Bratt, O., Montorsi, F., Volz, D., . . . Stattin, P. (2018). Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery. Journal of Surgical Oncology, 117(2), 321-327
Open this publication in new window or tab >>Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery
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2018 (English)In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 117, no 2, p. 321-327Article in journal (Refereed) Published
Abstract [en]

ObjectivesTo assess the use of post radical prostatectomy (RP) urinary incontinence (PPI) surgery and to investigate factors related to its use. MethodsCohort study in Prostate Cancer database Sweden (PCBaSe) of men who underwent primary RP between 1998 and 2012. PPI correction procedures were identified in the Patient Registry. Hazard ratios (HR) and 95% confidence intervals (CIs) of PPI surgeries were estimated. ResultsSeven hundred eighty-two out of 26280 (3%) men underwent PPI surgery at a median time of 3 years after RP. There was an eightfold increase in the absolute number of PPI surgeries during 2000-2014 and a threefold increase in the number per 1000 RPs performed. Factors associated with high use PPI surgery were age >70, HR 1.96 (1.54-2.50), and high hospital RP volume (>100 RPs/year), HR 0.81 (0.66-0.99). There was a 10-fold difference in use of PPI surgery per 1000 RPs between the county with the highest versus lowest use. In a subgroup of men with Patient-Reported Outcome Measures (PROM); severe PPI was reported by 7% of men and 24% of them underwent PPI surgery. ConclusionsThree percent of all men received PPI surgery, with a 10-fold variation among health care providers. Only a quarter of men with severe PPI underwent PPI surgery, suggesting that PPI surgery remains underutilized.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
artificial urinary sphincter, population based, post radical prostatectomy urinary incontinence, PROM
National Category
Nursing
Identifiers
urn:nbn:se:umu:diva-145787 (URN)10.1002/jso.24816 (DOI)000426165700026 ()28876467 (PubMedID)
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-06-09Bibliographically approved
Gnanapragasam, V. J., Bratt, O., Muir, K., Lees, L. S., Huang, H. H., Stattin, P. & Lophatananon, A. (2018). The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study. BMC Medicine, 16, Article ID 31.
Open this publication in new window or tab >>The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study
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2018 (English)In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, article id 31Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Prostate cancer, Prognostic prediction, Cancer-specific mortality, Cambridge Prognostic Groups, Non-metastatic disease, Stratification, All-cause mortality, Competing risks, Improved treatment section, Treatment selection
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-146163 (URN)10.1186/s12916-018-1019-5 (DOI)000426402000003 ()29490658 (PubMedID)
Available from: 2018-05-16 Created: 2018-05-16 Last updated: 2018-06-09Bibliographically approved
Lycken, M., Drevin, L., Garmo, H., Stattin, P., Adolfsson, J., Lissbrant, I. F., . . . Bill-Axelson, A. (2018). The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data. European Journal of Cancer, 88, 101-108
Open this publication in new window or tab >>The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 88, p. 101-108Article in journal (Refereed) Published
Abstract [en]

Background: Symptoms of terminal cancer have previously been reported as under-treated. The aim of this study was to assess the use of palliative medications before death from prostate cancer.

Methods: This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer.

Results: We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47-0.66 for > 85 years versus < 70 years) and (OR 0.78, 95% CI: 0.66-0.92 for unmarried without children versus married with children).

Conclusion: Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. 

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Anxiety, Cancer pain, Castration, Depression, Fatigue, Observational study, Opioids, Palliative medicine, Prostate cancer, Sleep disorders
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-143628 (URN)10.1016/j.ejca.2017.10.023 (DOI)000418290800012 ()29216521 (PubMedID)
Available from: 2018-01-29 Created: 2018-01-29 Last updated: 2018-06-09Bibliographically approved
Licciardello, M. P., Ringler, A., Markt, P., Klepsch, F., Lardeau, C.-H., Sdelci, S., . . . Kubicek, S. (2017). A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor. Nature Chemical Biology, 13(7), 771-778
Open this publication in new window or tab >>A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
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2017 (English)In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 13, no 7, p. 771-778Article in journal (Refereed) Published
Abstract [en]

Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-137623 (URN)10.1038/nchembio.2382 (DOI)000403673700014 ()28530711 (PubMedID)
Available from: 2017-07-19 Created: 2017-07-19 Last updated: 2018-06-09Bibliographically approved
Danneman, D., Drevin, L., Delahunt, B., Samaratunga, H., Robinson, D., Bratt, O., . . . Egevad, L. (2017). Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-2012. BJU International, 119(1), 50-56
Open this publication in new window or tab >>Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-2012
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2017 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, no 1, p. 50-56Article in journal (Refereed) Published
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).

Keywords
needle biopsy, pathology, prostate cancer, Gleason grade, #ProstateCancer, #PCSM
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-130217 (URN)10.1111/bju.13458 (DOI)000390401200012 ()
Available from: 2017-02-02 Created: 2017-01-14 Last updated: 2018-06-09Bibliographically approved
Stattin, P., Sandin, F., Birkebæk Thomsen, F., Garmo, H., Robinson, D., Franck Lissbrant, I., . . . Bratt, O. (2017). Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study. European Urology, 72(1), 125-134
Open this publication in new window or tab >>Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study
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2017 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 1, p. 125-134Article in journal (Refereed) Published
Abstract [en]

Background: Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance.

Objective: To investigate the association between radical local treatment and mortality in men with very high-risk PCa.

Design, setting, and participants: Semiecologic study of men aged <80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998–2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50–200 ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level <50 ng/ml, any N, and M0) were used as positive controls.

Intervention: Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis.

Outcome measurements and statistical analysis: PCa and all-cause mortality rate ratios (MRRs).

Results and limitations: Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28–0.95; and all-cause MRR: 0.56; 95% CI, 0.33–0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposure were in agreement with results from randomized trials (PCa MRR: 0.75; 95% CI, 0.60–0.94; and all-cause MRR: 0.85; 95% CI, 0.72–1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity.

Conclusions: The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective.

Patient summary: Men with very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Prostate cancer, Very high-risk, Radical, Treatment, Semiecologic, Nationwide, Population-based, PCBaSe
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-137374 (URN)10.1016/j.eururo.2016.07.023 (DOI)000403205900026 ()27481175 (PubMedID)
Available from: 2017-07-06 Created: 2017-07-06 Last updated: 2018-06-09Bibliographically approved
Schwartzbaum, J., Edlinger, M., Zigmont, V., Stattin, P., Rempala, G. A., Nagel, G., . . . Feychting, M. (2017). Associations between prediagnostic blood glucose levels, diabetes, and glioma. Scientific Reports, 7, Article ID 1436.
Open this publication in new window or tab >>Associations between prediagnostic blood glucose levels, diabetes, and glioma
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1436Article in journal (Refereed) Published
Abstract [en]

Previous literature indicates that pre-diagnostic diabetes and blood glucose levels are inversely related to glioma risk. To replicate these findings and determine whether they could be attributed to excess glucose consumption by the preclinical tumour, we used data from the Apolipoprotein MOrtality RISk (AMORIS) (n = 528,580) and the Metabolic syndrome and Cancer project (Me-Can) cohorts (n = 269,365). We identified individuals who were followed for a maximum of 15 years after their first blood glucose test until glioma diagnosis, death, emigration or the end of follow-up. Hazard ratios (HRs), 95% confidence intervals (CIs) and their interactions with time were estimated using Cox time-dependent regression. As expected, pre-diagnostic blood glucose levels were inversely related to glioma risk (AMORIS, P-trend = 0.002; Me-Can, P-trend = 0.04) and pre-diagnostic diabetes (AMORIS, HR = 0.30, 95% CI 0.17 to 0.53). During the year before diagnosis, blood glucose was inversely associated with glioma in the AMORIS (HR = 0.78, 95% CI 0.66 to 0.93) but not the Me-Can cohort (HR = 0.99, 95% CI 0.63 to 1.56). This AMORIS result is consistent with our hypothesis that excess glucose consumption by the preclinical tumour accounts for the inverse association between blood glucose and glioma. We discuss additional hypothetical mechanisms that may explain our paradoxical findings.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-136189 (URN)10.1038/s41598-017-01553-2 (DOI)000400491700012 ()28469238 (PubMedID)
Available from: 2017-07-07 Created: 2017-07-07 Last updated: 2018-06-09Bibliographically approved
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