| 1. |
- 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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| 2. |
- Speakman, John R., et al.
(författare)
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
- 2023
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Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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| 3. |
- Atun, Rifat, et al.
(författare)
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Sustainable care for children with cancer : a Lancet Oncology Commission
- 2020
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Ingår i: The Lancet Oncology. - 1470-2045. ; 21:4, s. 185-224
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Forskningsöversikt (refereegranskat)abstract
- We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
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| 4. |
- Buschur, Kristina L., et al.
(författare)
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Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease
- 2024
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Ingår i: Annals of the American Thoracic Society. - : American Thoracic Society. - 2329-6933 .- 2325-6621. ; 21:6, s. 884-894
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.
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