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024 7 _ |a 10.1210/clinem/dgad212
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024 7 _ |a 0368-1610
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024 7 _ |a 0021-972X
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024 7 _ |a 1945-7197
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037 _ _ |a DKFZ-2023-00776
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Mukama, Trasias
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245 _ _ |a IGF-1 and risk of morbidity and mortality from cancer, cardiovascular diseases, and all-causes in EPIC - Heidelberg.
260 _ _ |a Oxford
|c 2023
|b Oxford University Press
336 7 _ |a article
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500 _ _ |a #EA:C020#LA:C020# / 2023 Sep 18;108(10):e1092-e1105
520 _ _ |a The functional status of organs involved in IGF-1 signalling pathways such as the liver influence circulating levels of IGF-1 and hence its relationship with risk of chronic diseases and mortality, yet has received limited attention.To examine the relationship between IGF-1 and risk of morbidity and mortality from cancer, cardiovascular diseases and all-causes, accounting for liver function.Case-cohort design nested within EPIC-Heidelberg. IGF-1 was measured in 7,461 stored serum samples collected from 1994 to 1998. Median follow-up for incident mortality events: 17.5 years.General community.The case-cohort included a subcohort of 1,810 men and 1,890 women, in addition to 1668 incident cases of cancer (623 breast, 577 prostate, 202 lung and 268 colorectal cancers), and 1428 cases of CVD (707 MIs and 723 strokes) and 2441 cases of death.Higher IGF-1 levels showed direct associations with risks of breast (1.25 95% CI: [1.06-1.47]) and prostate (1.31 [1.09-1.57]) cancers. Restricted cubic splines plots and models including IGF-1 as quintiles revealed a U-shaped relationship between the biomarker and mortality. Both participants with lowest and highest levels of IGF-1 experienced higher hazards of mortality from cancer, cardiovascular diseases and all-causes. The U-shaped form of the relationship persisted but was attenuated in analyses including only participants without any indications of liver dysfunction.This large population-based prospective study showed that both individuals with lowest and highest levels of circulating IGF-1 were at increased risk of deaths from cancer, cardiovascular and all-causes. For individuals with low IGF-1, the excess risks of death were more pronounced among individuals with liver cancer and cirrhosis but were also present among individuals without elevated liver enzymes.
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650 _ 7 |a IGF-1
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650 _ 7 |a cancer
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650 _ 7 |a cardiovascular diseases
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650 _ 7 |a liver enzymes
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650 _ 7 |a liver function
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650 _ 7 |a mortality
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700 1 _ |a Srour, Bernard
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700 1 _ |a Johnson, Theron
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700 1 _ |a Katzke, Verena
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700 1 _ |a Kaaks, Rudolf
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773 _ _ |a 10.1210/clinem/dgad212
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