| 1. |
- Wang, Anqi, et al.
(författare)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
|
|
| 2. |
- Conti, David, V, et al.
(författare)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 3. |
- Heijnsdijk, Eveline A M, et al.
(författare)
-
Quality-of-life effects of prostate-specific antigen screening.
- 2012
-
Ingår i: The New England journal of medicine. - 1533-4406. ; 367:7, s. 595-605
-
Tidskriftsartikel (refereegranskat)abstract
- After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain.
|
|
| 4. |
|
|
| 5. |
- Schröder, Fritz H, et al.
(författare)
-
Prostate-cancer mortality at 11 years of follow-up.
- 2012
-
Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 366:11, s. 981-90
-
Tidskriftsartikel (refereegranskat)abstract
- Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up.
|
|
| 6. |
- Schröder, Fritz H, et al.
(författare)
-
Screening and prostate-cancer mortality in a randomized European study.
- 2009
-
Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 360:13, s. 1320-8
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer.
|
|
| 7. |
|
|
| 8. |
- Roobol, Monique J., et al.
(författare)
-
Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)
- 2009
-
Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:4, s. 584-591
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (Cis) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of over diagnosis and overtreatment inherent in PCa screening. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
|
|
| 9. |
|
|
| 10. |
- Carlsson, Sigrid, 1982, et al.
(författare)
-
Could Differences in Treatment Between Trial Arms Explain the Reduction in Prostate Cancer Mortality in the European Randomized Study of Screening for Prostate Cancer?
- 2019
-
Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 75:6, s. 1015-1022
-
Tidskriftsartikel (refereegranskat)abstract
- Differential treatment between trial arms has been suggested to bias prostate cancer (PC) mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC).To quantify the contribution of treatment differences to the observed PC mortality reduction between the screening arm (SA) and the control arm (CA).A total of 14 136 men with PC (SA: 7310; CA: 6826) in the core age group (55-69yr) at 16yr of follow-up.The outcomes measurements were observed and estimated numbers of PC deaths by treatment allocation in the SA and CA, respectively. Primary treatment allocation was modeled using multinomial logistic regression adjusting for center, age, year, prostate-specific antigen, grade group, and tumor-node-metastasis stage. For each treatment, logistic regression models were fitted for risk of PC death, separately for the SA and CA, and using the same covariates as for the treatment allocation model. Treatment probabilities were multiplied by estimated PC death risks for each treatment based on one arm, and then summed and compared with the observed number of deaths.The difference between the observed and estimated treatment distributions (hormonal therapy, radical prostatectomy, radiotherapy, and active surveillance/watchful waiting) in the two arms ranged from -3.3% to 3.3%. These figures, which represent the part of the treatment differences between arms that cannot be explained by clinicopathological differences, are small compared with the observed differences between arms that ranged between 7.2% and 10.1%. The difference between the observed and estimated numbers of PC deaths among men with PC was 0.05% (95% confidence interval [CI] -0.1%, 0.2%) when applying the CA model to the SA, had the two groups received identical primary treatment, given their clinical characteristics. When instead applying the SA model to the CA, the difference was, as expected, very similar-0.01% (95% CI -0.3%, 0.2%). Consistency of the results of the models demonstrates the robustness of the modeling approach. As the observed difference between trial arms was 4.2%, our findings suggest that differential treatment explains only a trivial proportion of the main findings of ERSPC. A limitation of the study is that only data on primary treatment were available.Use of prostate-specific antigen remains the predominant explanation for the reduction in PC mortality seen in the ERSPC trial and is not attributable to differential treatment between trial arms.This study shows that prostate cancer deaths in the European screening trial (European Randomized Study of Screening for Prostate Cancer) were prevented because men were diagnosed and treated earlier through prostate-specific antigen screening, and not because of different, or better, treatment in the screening arm compared with the control arm.
|
|
