| 41. |
- FitzGerald, L. M., et al.
(författare)
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Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality : an analysis of 12,082 prostate cancer cases
- 2018
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 21:2, s. 228-237
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 42. |
- Franck-Lissbrant, Ingela, 1969, et al.
(författare)
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Population-based study on use of chemotherapy in men with castration resistant prostate cancer
- 2013
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 52:8, s. 1593-1601
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Tidskriftsartikel (refereegranskat)abstract
- Background. Chemotherapy prolongs life and relieves symptoms in men with castration resistant prostate cancer (CRPC). There is limited information on a population level on the use of chemotherapy for CRPC. Material and methods. To assess the use of chemotherapy in men with CRPC we conducted a register-based nationwide population-based study in Prostate Cancer data Base Sweden (PCBaSe) and a nationwide in-patient drug register (SALT database) between May 2009 and December 2010. We assumed that men who died of prostate cancer (PCa) underwent a period of CRPC before they died. Results. Among the 2677 men who died from PCa during the study inclusion period, 556 (21%) had received chemotherapy (intravenous or per oral) detectable within the observation period in SALT database. Specifically, 239 (61%) of men <70 years had received chemotherapy, 246 (30%) of men between 70 and 79 years and 71 (5%) men older than 80 years. The majority of men 465/556 (84%) had received a docetaxel-containing regimen. Among chemotherapy treated men, 283/556 (51%) received their last dose of chemotherapy during the last six months prior to death. Treatment with chemotherapy was more common among men with little comorbidity and high educational level, as well as in men who had received curatively intended primary treatment. Conclusion. A majority of men younger than 70 years with CRPC were treated with chemotherapy in contrast to men between 70 and 79 years of whom half as many received chemotherapy. Chemotherapy treatment was often administered shortly prior to death. The low uptake of chemotherapy in older men with CRPC may be caused by concerns about tolerability of treatment, as well as treatment decisions based on chronological age rather than global health status.
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| 45. |
- George, G., et al.
(författare)
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Risk of cardiovascular events in men on abiraterone or enzalutamide combined with GnRH agonists: nation-wide, population-based cohort study in Sweden
- 2021
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:4, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated. Material and methods We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSeTraject) 4.1 between 1 June 2015 and 31 December 2018. PCBaSeTraject links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome. Results and conclusion 1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03-1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01-1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.
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| 50. |
- Jansson, F., et al.
(författare)
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Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer
- 2018
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 36:18, s. 1847-1852
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Tidskriftsartikel (refereegranskat)abstract
- PurposeProstate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation.MethodsWe identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)ResultsAmong monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.ConclusionNon-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.
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