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- Watts, Eleanor L., et al.
(författare)
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Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:7, s. 1033-1046
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
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| 2. |
- Watts, Eleanor L., et al.
(författare)
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Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
- 2023
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:1, s. 71-86
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer.Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium.Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I.Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
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| 3. |
- Jennings, Anne E., et al.
(författare)
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Baffin Bay paleoenvironments in the LGM and HS1 : Resolving the ice-shelf question
- 2018
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Ingår i: Marine Geology. - : Elsevier BV. - 0025-3227 .- 1872-6151. ; 402, s. 5-16
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Tidskriftsartikel (refereegranskat)abstract
- Core HU2008029-12PC from the Disko trough mouth fan on the central West Greenland continental slope is used to test whether an ice shelf covered Baffin Bay during the Last Glacial Maximum (LGM) and at the onset of the deglaciation. We use benthic and planktic foraminiferal assemblages, stable isotope analysis of planktic forams, algal biomarkers, ice-rafted detritus (IRD), lithofacies characteristics defined from CT scans, and quantitative mineralogy to reconstruct paleoceanographic conditions, sediment processes and sediment provenance. The chronology is based on radiocarbon dates on planktic foraminifers using a Delta R of 140 +/- 30 C-14 years, supplemented by the varying reservoir estimates of Stern and Lisiecki (2013) that provide an envelope of potential ages. HU2008029-12PC is bioturbated throughout. Sediments between the core base at 11.3 m and 4.6 m (LGM through HS1) comprise thin turbidites, plumites and hemipelagic sediments with Greenlandic provenance consistent with processes active at the Greenland Ice Sheet margin grounded at or near the shelf edge. Abundance spikes of planktic forams coincide with elevated abundance of benthic forams in assemblages indicative of chilled Atlantic Water, meltwater and intermittent marine productivity. IRD and IP25 are rare in this interval, but brassicasterol, an indicator of marine productivity reaches and sustains low levels during the LGM. These biological characteristics are consistent with a sea-ice covered ocean experiencing periods of more open water such as leads or polynyas in the sea ice cover, with chilled Atlantic Water at depth, rather than full iceshelf cover. They do not support the existence of a full Baffin Bay ice shelf cover extending from grounded ice on the Davis Strait. Initial ice retreat from the West Greenland margin is manifested by a pronounced lithofacies shift to bioturbated, diatomaceous mud with rare IRD of Greenlandic origin at 467 cm (16.2 cal ka BP; Delta R = 140 yrs) within HS1. A spike in foraminiferal abundance and ocean warmth indicator benthic forams precedes the initial ice retreat from the shelf edge. At the end of HS1, IP 25 , brassicasterol and benthic forams indicative of sea-ice edge productivity increase, indicating warming interstadial conditions. Within the Bolling/Allerod interstadial a strong rise in IP 25 content and IRD spikes rich in detrital carbonate from northern Baffin Bay indicate that northern Baffin Bay ice streams were retreating and provides evidence for increased open water, advection of Atlantic Water in the West Greenland Current, and formation of an IRD belt along the W. Greenland margin.
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