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- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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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.
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| 2. |
- Gandaglia, Giorgio, et al.
(författare)
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Epidemiology and Prevention of Prostate Cancer
- 2021
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 4:6, s. 877-892
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Worldwide, prostate cancer (PCa) represents the second most common solid tumor in men.OBJECTIVE: To assess the geographical distribution of PCa, epidemiological differences, and the most relevant risk factors for the disease.EVIDENCE ACQUISITION: Estimated incidence, mortality, and prevalence of PCa for the year 2020 in 185 countries were derived from the IARC GLOBOCAN database. A review of English-language articles published between 2010 and 2020 was conducted using MEDLINE, EMBASE, and Scopus to identify risk factors for PCa.EVIDENCE SYNTHESIS: In the year 2020, there were over 1414000 estimated new cases of PCa worldwide, with an age-standardized rate (ASR) incidence of 31 per 100000 (lifetime cumulative risk: 3.9%). Northern Europe has the highest all-age incidence ASR (83), while the lowest ASR was in South-Central Asia (6.3). In the year 2020, there were over 375000 estimated deaths worldwide, and the overall mortality ASR was 7.7 per 100000, with the highest ASR in the Caribbean (28) and the lowest in South-Central Asia (3.1). Family history, hereditary syndromes, and race are the strongest risk factors for PCa. Metabolic syndrome was associated with the risk of developing PCa, high-grade disease, and adverse pathology. Diabetes and exposure to ultraviolet rays were found to be inversely associated to PCa incidence. Cigarette smoking and obesity may increase PCa-specific mortality, while regular physical activity may reduce disease progression. Although 5-alpha reductase inhibitors are known to be associated with a reduced incidence of PCa, available studies failed to show an effect on overall mortality.CONCLUSIONS: Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.PATIENT SUMMARY: Prostate cancer (PCa) rates vary profoundly worldwide, with incidence and mortality rates being highest in Northern Europe and Caribbean, respectively. South-Central Asia has the lowest epidemiological burden. Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease itself, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.
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| 4. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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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.
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