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- Larsson, Susanna C, et al.
(author)
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Association of diet with serum insulin-like growth factor I in middle-aged and elderly men
- 2005
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 81:5, s. 1163-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: Insulin-like growth factor I (IGF-I) has been implicated in several chronic diseases, including cancer, heart disease, and osteoporosis.OBJECTIVE: Our aim was to assess whether intakes of total energy, alcohol, vitamins, minerals, and foods rich in protein and minerals (including red meat, fish and seafood, poultry, and milk) are associated with serum IGF-I concentrations in middle-aged and elderly men.DESIGN: We measured serum IGF-I concentrations in 226 free-living healthy men aged 42-76 y. The average of fourteen 24-h dietary telephone interviews performed over 1 y was used to estimate long-term dietary intake.RESULTS: We observed statistically significant positive associations between intakes of protein (P for trend = 0.001) and zinc (P for trend = 0.002) and serum IGF-I concentrations after adjusting for age. The difference in mean IGF-I concentrations for the highest compared with the lowest quintile of intake was approximately 17% (162 microg/L compared with 139 microg/L) for protein and approximately 16% (166 microg/L compared with 143 microg/L) for zinc. Consumption of red meat (P for trend = 0.05) and fish and seafood (P for trend = 0.07) was modestly positively associated with IGF-I concentrations. Other dietary factors were not associated with IGF-I concentrations.CONCLUSION: In this population of healthy well-nourished men, greater dietary intakes of protein, zinc, red meat, and fish and seafood were associated with higher IGF-I concentrations.
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- Conti, David, V, et al.
(author)
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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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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)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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- Huyghe, Jeroen R., et al.
(author)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Journal article (peer-reviewed)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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5. |
- Svedbom, Axel, et al.
(author)
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Long-term Outcomes and Prognosis in New-Onset Psoriasis
- 2021
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In: JAMA dermatology. - : American Medical Association (AMA). - 2168-6068 .- 2168-6084. ; 157:6, s. 684-690
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Journal article (peer-reviewed)abstract
- Importance Psoriasis is a heterogeneous disease. Improved understanding of prognosis and long-term outcomes in new-onset psoriasis may improve care.Objective To describe the clinical course of psoriasis and identify possible indicators of long-term outcomes.Design, Setting and Participants The Stockholm Psoriasis Cohort was a noninterventional inception cohort study enrolling patients between 2001 and 2005. The present study was conducted from January 15, 2019, to February 5, 2021. At enrollment and 10 years, patients were examined by dermatologists and rheumatologists. Data from examinations were complemented by questionnaires, medical records, and registers. A total of 721 patients with recent-onset psoriasis (<12 months duration), 15 years or older were recruited using advertising and referrals from a broad range of health care settings.Main Outcomes and Measures Disease severity and psoriatic arthritis (PsA). Recursive partitioning and regression models were implemented to identify probable indicators of long-term outcomes.Results A total of 721 patients (median [interquartile range] age, 39 [27-55] years; 405 [56%] women), including 542 (75%) with plaque-onset and 174 (24%) with guttate-onset psoriasis, were enrolled. The median follow-up was 9.6 years (interquartile range, 8.8-10.4 years). The cumulative incidence of severe psoriasis at 12 years from enrollment was 21%. Among 509 patients examined clinically after 10 years, 77 of 389 patients (20%) with plaque onset and 56 of 116 (48%) with guttate onset had minimal disease activity without treatment, and 120 of 509 (24%) had PsA. Recursive partitioning identified strata with distinct risks for severe skin disease and PsA: the cumulative incidence of severe disease in patients with plaque phenotype, above-median disease activity, and scalp lesions was 52% (95% CI, 41%-64%), compared with 11% (95% CI, 8%-14%) in patients with below-median disease activity at inclusion; and 48 of 82 patients (59%) with peripheral enthesitis had PsA after 10 years compared with 37 of 304 patients (12%) without initial joint pain (P < .001). Smoking (hazard ratio, 1.70; 95% CI, 1.10-2.63) and activating genes in the interleukin-23 (IL-23) pathway (odds ratio, 1.55; 95% CI, 1.14-2.11) were also significantly associated with a severe disease course. Systemic therapy at or before enrollment was associated with a lower risk for severe disease at 10 years compared with later initiation of systemic therapy (odds ratio, 0.24; 95% CI, 0.06-0.90).Conclusions and Relevance The findings of this cohort study suggest that combinations of clinical characteristics at onset and activating genes in the IL-23 pathway are significantly associated with the clinical course of psoriasis, whereas joint pain and peripheral enthesitis may indicate the probability of PsA. Patients within those categories merit specialist referral and closer follow-up. The possibility of modifying the disease course with early systemic intervention should be tested.
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6. |
- Wolk, Katarina, et al.
(author)
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Excessive body weight and smoking associates with a high risk of onset of plaque psoriasis
- 2009
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In: Acta Dermato-Venereologica. - : Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 89:5, s. 492-497
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Journal article (peer-reviewed)abstract
- Accumulating evidence indicates that body weight, alcohol and smoking are associated with psoriasis. However, these factors have scarcely been investigated in relation to onset and disease activity at onset of psoriasis. A population-based case-control study was performed including 373 cases with onset of first-time plaque psoriasis within 12 months and matched healthy controls. Psoriasis activity was measured using the Psoriasis Area and Severity Index (PASI). Analyses were performed using conditional logistic regression. In multivariable analyses for each unit increment in body mass index, there was statistically significant 9% increased risk for psoriasis onset and 7% higher risk for increased PASI. Obesity (body mass index ≥ 30) compared with normal body weight was associated with a two-fold increased risk for psoriasis onset. Smoking was associated with a 70% increased risk for onset, but was not related to PASI. A positive association with alcohol drinking was observed among men, but not among women. No associations were observed for weight gain and use of smokeless tobacco. Our results indicate that excessive body weight and smoking are risk factors for onset of psoriasis and that higher body mass index increases the PASI of plaque psoriasis at onset.
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