56 research outputs found
Socioeconomic position and lifestyle in relation to breast cancer incidence among postmenopausal women: A prospective cohort study, Denmark, 1993-2006
No full textBackground: In Denmark, the incidence of breast cancer is higher among women with higher socioeconomic position. We investigated whether differences in exposure to certain risk factors contribute to this gradient, as measured from education, income and occupation. Methods: We conducted a cohort study of 23 111 postmenopausal women aged 50-65 years who were enrolled in the prospective Danish 'Diet, Cancer and Health' study between 1993 and 1995. At baseline, all women filled in a questionnaire on lifestyle and food frequency. The results were analysed in Cox proportional hazard models. Results: Part of the association with socioeconomic position is due to the potential mediators reproductive pattern, use of hormone replacement therapy and alcohol consumption. After simultaneous adjustment for these factors, the hazard ratios were 1.06 (95% confidence interval [CI], 0.88-1.27) for women with higher education and 1.07 (95% CI 0.85-1.34) for women with higher income. The HR ratio for women working as higher officials when compared with unskilled workers was 1.23 (0.96-1.59). Conclusion: The results support the hypothesis that the higher incidence of breast cancer among socially advantaged women is mediated partly by differences in exposure to reproductive factors, hormone replacement therapy and alcohol.Signe Benzon Larsen, Anja Olsen, John Lynch, Jane Christensen, Kim Overvad, Anne Tjønneland, Christoffer Johansen, Susanne Oksbjerg Dalto
Pro and con for systematic screening for prostate cancer in Denmark - a review article
No full textSystematic PSA-based screening for prostate cancer remains controversial due to the trade-off between reduced mortality and risk of overdiagnosis and overtreatment. Adding new tools like magnetic-resonance-imaging-targeted biopsies and genetic markers may limit the harms, but we lack definitive mortality data. While opportunistic PSA testing is widely used in Denmark, unsystematic use may potentially be harmful. Introduction of a systematic screening programme in Denmark requires careful consideration of the clinical, psychological, societal and economic impacts, and Danish politicians should thus engage in the debate to clarify these issues.</p
Polymorphisms in alcohol dehydrogenase and perixosome proliferator-activated receptor-g-2 and breast cancer risk in relation to alcohol consumption
No full textPerfluorooctanoate and Perfluorooctanesulfonate plasma concentrations and survival after prostate and bladder cancer in a population-based study
No full textAlternativ splicing i HOF og ZNF499
No full textAlternativ splicing beskrives i de homologe HOF- og ZNF499-gener. Genprodukterne af HOF og ZNF499 er DNA-bindende, zinkfingerproteiner, hvert indeholdende et BTB/POZ-domæne. Hvor HOF er medvirkende i udviklingen af den mammale hjerne, er funktionen af genproduktet for ZNF499 endnu ukendt. cDNA for HOF og ZNF499 er indsat i en vektor og herefter sekvenseret. For HOF er der fundet nye spliceformer, hvori fem nye exons er identificeret og lokaliseret. Herved er 5´enden af genet kortlagt. Den er en ny længde af HOF bestemt til 700 kb. Disse spliceformer er desuden udtrykt ved proteinekspression, hvor to isoformer af HOF fremkommer. Sekvensen omkring translationsstartsite i de forskellige exons analyseres og sammenlignes med Kozak konsensus sekvensen. For ZNF499 er alternative spliceformer fundet og nye exons er identificeret og lokaliseret. The alternative splicing of the HOF and ZNF499 genes is described. The gene product of HOF and ZNF499 are DNA binding Zinc finger proteins, each containing a BTB/POZ domain. HOF is known to be involved in the development of the mammalian brain. The function of the ZNF499 gene product is unknown. cDNA from HOF and ZNF499 was inserted into a vector and sequenced. New HOF splice forms were found and used for localizing five new exons. Thereby the 5´ end of the gene was mapped. The new length of HOF was found to be 700 kb. The splice forms were expressed, resulting in two isoforms of HOF. The regions around the start sites of the different exons were analysed compared with the consensus derived by Kozak Alternative splice forms of ZNF499 were also found, and new exons localized.Alternativ splicing beskrives i de homologe HOF- og ZNF499-gener. Genprodukterne af HOF og ZNF499 er DNA-bindende, zinkfingerproteiner, hvert indeholdende et BTB/POZ-domæne. Hvor HOF er medvirkende i udviklingen af den mammale hjerne, er funktionen af genproduktet for ZNF499 endnu ukendt. cDNA for HOF og ZNF499 er indsat i en vektor og herefter sekvenseret. For HOF er der fundet nye spliceformer, hvori fem nye exons er identificeret og lokaliseret. Herved er 5´enden af genet kortlagt. Den er en ny længde af HOF bestemt til 700 kb. Disse spliceformer er desuden udtrykt ved proteinekspression, hvor to isoformer af HOF fremkommer. Sekvensen omkring translationsstartsite i de forskellige exons analyseres og sammenlignes med Kozak konsensus sekvensen. For ZNF499 er alternative spliceformer fundet og nye exons er identificeret og lokaliseret. The alternative splicing of the HOF and ZNF499 genes is described. The gene product of HOF and ZNF499 are DNA binding Zinc finger proteins, each containing a BTB/POZ domain. HOF is known to be involved in the development of the mammalian brain. The function of the ZNF499 gene product is unknown. cDNA from HOF and ZNF499 was inserted into a vector and sequenced. New HOF splice forms were found and used for localizing five new exons. Thereby the 5´ end of the gene was mapped. The new length of HOF was found to be 700 kb. The splice forms were expressed, resulting in two isoforms of HOF. The regions around the start sites of the different exons were analysed compared with the consensus derived by Kozak Alternative splice forms of ZNF499 were also found, and new exons localized
Early experience with targeted and combination biopsies in prostate cancer work-up in Denmark from 2012 to 2016
No full textPurposeTo investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology.MethodsThis population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen’s Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator.ResultsConcordance between biopsy and RP pathology was 0.53 (95CI: 0.43–0.63), 0.38 (95CI: 0.29–0.48), and 0.16 (95CI: 0.11–0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27–0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62–0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11–32), 30% (95CI: 15–44), and 19% (95CI: 7.0–30) in GG 5 for cBx, tBx, or sBx, respectively.ConclusionOverall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment.Purpose: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology. Methods: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen’s Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator. Results: Concordance between biopsy and RP pathology was 0.53 (95CI: 0.43–0.63), 0.38 (95CI: 0.29–0.48), and 0.16 (95CI: 0.11–0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27–0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62–0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11–32), 30% (95CI: 15–44), and 19% (95CI: 7.0–30) in GG 5 for cBx, tBx, or sBx, respectively. Conclusion: Overall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment.</p
hyperglykemisk induceret oxidativt stress fører til udvikling af diabetiske komlikationer
No full textI denne rapport beskrives, hvordan hyperglykæmi inducerer øget oxidativt stress. Dette sker gennem de fem signalveje, elektrontransportkæden, polyol-signalvejen, hexosamin-signalvejen, protein kinase C og AGE-dannelsen. Da pancreas har et nedsat niveau af forsvarsenzymer mod ROS, kan et forøget oxidativt stress medføre en destruktion af β-celler i de Langerhanske øer. Ved destruktionen af β-celler fremkommer tilstanden hyperglykæmi, som følge af blandt andet nedsat insulinsekretion eller reduceret glucoseoptag. ROS kan aktivere af en række signalveje, der kan føre til mikro- og makrovaskulære skader, herunder retinopati, neuropati, nephropapati. Der forskes intensivt i at afdække de molekylærbiologiske mekanismer for at forbedre forebyggelse og behandling af udviklingen af diabetiske komplikationer. Denne rapport behandler, hvordan komplikationer kan undgås ved brugen af forskellige medikamenter, som blandt andet reducerer niveauet af oxidativt stress. Om disse medikamenter kan anvendes på patienter, kræver kliniske forsøg som dokumentation for effekten af disse.I denne rapport beskrives, hvordan hyperglykæmi inducerer øget oxidativt stress. Dette sker gennem de fem signalveje, elektrontransportkæden, polyol-signalvejen, hexosamin-signalvejen, protein kinase C og AGE-dannelsen. Da pancreas har et nedsat niveau af forsvarsenzymer mod ROS, kan et forøget oxidativt stress medføre en destruktion af β-celler i de Langerhanske øer. Ved destruktionen af β-celler fremkommer tilstanden hyperglykæmi, som følge af blandt andet nedsat insulinsekretion eller reduceret glucoseoptag. ROS kan aktivere af en række signalveje, der kan føre til mikro- og makrovaskulære skader, herunder retinopati, neuropati, nephropapati. Der forskes intensivt i at afdække de molekylærbiologiske mekanismer for at forbedre forebyggelse og behandling af udviklingen af diabetiske komplikationer. Denne rapport behandler, hvordan komplikationer kan undgås ved brugen af forskellige medikamenter, som blandt andet reducerer niveauet af oxidativt stress. Om disse medikamenter kan anvendes på patienter, kræver kliniske forsøg som dokumentation for effekten af disse
Epidemiology of men with synchronous metastatic prostate cancer diagnosis – A nationwide 26-year temporal analysis
No full textBackground: Evolving imaging modalities, increased awareness, and prostate-specific antigen testing in men with synchronous metastatic prostate cancer (mHSPC) are expected to have prolonged survival. Here we analyze trends in survival among men diagnosed with synchronous metastatic prostate cancer in Denmark. Methods: Here, we included all men diagnosed with mHSPC (N = 12,017) in Denmark between January 1st, 1995, and December 31st, 2021. Men were followed until December 31st, 2022. Median time to death was calculated by the Kaplan Meier method and the 3-year risk of prostate cancer death per calendar year was estimated by the Aalen-Johansen estimator from time of diagnosis. Findings: Median follow-up was 9 years (IQR: 4–15), from 2015 59 % of the men with mHSPC had treatment beyond androgen depletion therapy. Median survival increased from 1.7 years (IQR: 1·3–2·0) to 3.8 years (IQR: 3·3–4·2) in men diagnosed in 1995 and 2018, respectively (p < 0·001), after which median survival was not reached. The prostate cancer-specific mortality three years after diagnosis decreased from 66 % (95 %CI: 60–72) in 1995 to 28 % (95 %CI: 25–32) in 2019 (p < 0·001). From the period 1995–1999 to 2015–2021 median overall survival increased from 1·7 years (IQR: 0·8–3·7) to 4·5 years (IQR: 2·4-not reached; p < 0·001) in men age < 65 years and from 1·5 years (IQR: 0·7–2·9) to 3·1 years (IQR: 1·6–5·7; p < 0.001) in men older than 74 years at diagnosis. Interpretation: The improved survival suggests that, among other contributing factors, implementing novel therapies has likely been efficacious outside the clinical trial setting. Still, most men diagnosed with synchronous metastatic prostate cancer will die of prostate cancer. As such the need for life-prolonging and age-tailored treatment trials remains evident.</p
Influence of metabolic indicators, smoking, alcohol and socioeconomic position on mortality after breast cancer
No full textBACKGROUND: Factors differently distributed among social groups like obesity, metabolic syndrome, diabetes, smoking, and alcohol intake predict survival after breast cancer diagnosis and therefore might mediate part of the observed social inequality in survival.MATERIAL AND METHODS: We conducted a cohort study among 1250 postmenopausal breast cancer patients identified among 29 875 women in the Danish Diet, Cancer and Health Study. Participants completed questionnaires and anthropometric measurements were made at enrollment. Information on survival, socioeconomic position, and comorbidity was obtained by linkage to national Danish registries. Clinical information was obtained from the nationwide Danish Breast Cancer Database. Selected information was obtained from hospital records at time of diagnosis. All analyses were based on Cox proportional hazard models, using death from all causes as outcome.RESULTS: Median follow-up was 9.6 years [interquartile range (IQR), 2.2-17.0 years]. The hazard ratio (HR) for death from all causes increased with lower education (p for trend, 0.01). Adjustment for disease-related prognostic factors, comorbidity and metabolic indicators measured as BMI, waist circumference and diabetes, and smoking and alcohol affected but did not explain the social gradient.CONCLUSION: The findings indicate that these factors explain some but not all the social inequality in survival after breast cancer and that improvement of lifestyle to some extent would improve survival among women with low socioeconomic position.</p
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