| 1. |
- 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. |
- 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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| 3. |
- Andreasson, Anna Nixon, et al.
(författare)
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Inflammation and positive affect are associated with subjective health in women of the general population
- 2013
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Ingår i: Journal of Health Psychology. - : SAGE Publications. - 1359-1053 .- 1461-7277. ; 18:3, s. 311-320
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Tidskriftsartikel (refereegranskat)abstract
- Poor subjective health has been associated with higher levels of inflammatory cytokines. We investigated whether such an association would apply to women of the general population. Levels of cytokines, affect and subjective health were assessed in 347 women of the general population aged 45 to 90 years. Higher levels of interleukin-6 were associated with poor subjective health, especially in participants over 65 years of age. Positive affect was a more robust determinant of subjective health than negative affect. The presence of low-grade inflammation and absence of positive affect, rather than presence of negative affect, may be important determinants of subjective health.
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| 4. |
- Bonn, Stephanie E., et al.
(författare)
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Body mass index and weight change in men with prostate cancer : progression and mortality
- 2014
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Ingår i: Cancer Causes and Control. - : Springer Netherlands. - 0957-5243 .- 1573-7225. ; 25:8, s. 933-943
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Tidskriftsartikel (refereegranskat)abstract
- Body mass index (BMI) is a modifiable lifestyle factor that has been associated with an increased risk of fatal prostate cancer and biochemical recurrence. The main purpose of the present study was to investigate the association between the exposure BMI at the time of a prostate cancer diagnosis and weight change after diagnosis, and the outcomes of prostate cancer progression and mortality in a large cohort study. Data from 4,376 men diagnosed with clinically localized prostate cancer between 1997 and 2002 were analyzed. BMI and weight change were self-reported in 2007. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated in complete-case analysis (n = 3,214) using Cox proportional hazards models. Progression was experienced among 639 (14.6 %) of the study participants, and in total, 450 (10.3 %) deaths of any cause and 134 (3.1 %) prostate cancer-specific deaths were recorded during follow-up. Obese men had a 47 % increased rate of overall mortality compared to normal weight men (HR 1.47, 95 % CI 1.03-2.10). No statistically significant associations were found for BMI and prostate cancer progression or prostate cancer-specific mortality. A weight loss > 5 % after diagnosis almost doubled the rate of overall mortality compared to maintaining a stable weight (HR 1.94, 95 % CI 1.41-2.66), while a weight gain > 5 % was associated with an almost doubled increased rate of prostate cancer-specific mortality (HR 1.93, 95 % CI 1.18-3.16). Being obese was associated with an increased rate of overall mortality, and gaining weight after a prostate cancer diagnosis was associated with an increased rate of prostate cancer-specific mortality.
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| 5. |
- de Boniface, Jana, et al.
(författare)
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Completion axillary lymph node dissection for the identification of pN2–3 status as an indication for adjuvant CDK4/6 inhibitor treatment : a post-hoc analysis of the randomised, phase 3 SENOMAC trial
- 2024
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 25:9, s. 1222-1230
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Tidskriftsartikel (refereegranskat)abstract
- Background: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1–2, grade 1–2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2–3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial.Methods: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1–T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1–2, histological grade 1–2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing.Findings: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52–71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6–59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery.Interpretation: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. Funding: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.
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| 6. |
- Kawakami, Naomi, et al.
(författare)
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Differences in neighborhood accessibility to health-related resources : A nationwide comparison between deprived and affluent neighborhoods in Sweden
- 2011
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Ingår i: Health and Place. - : Elsevier BV. - 1353-8292 .- 1873-2054. ; 17:1, s. 132-139
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Tidskriftsartikel (refereegranskat)abstract
- This nationwide Swedish study used geocoded data from all businesses in Sweden to examine the distribution of 12 main categories of goods, services, and resources in 6986 neighborhoods, categorized as low, moderate, and high neighborhood deprivation. The main findings were that high- and moderate-deprivation neighborhoods had a significantly higher prevalence of all types of goods, services, and resources than low-deprivation neighborhoods. These findings do not support previous research that hypothesizes that poorer health among people in deprived neighborhoods is explained by a lack of health-promoting resources, although a higher presence of health-damaging resources may play a role. (C) 2010 Elsevier Ltd. All rights reserved.
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| 7. |
- Nager, Anna, et al.
(författare)
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High lifelong relapse rate of psychiatric disorders among women with postpartum psychosis
- 2013
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 67:1, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Nager A, Szulkin R, Johansson S-E, Johansson L-M, Sundquist K. High lifelong relapse rate of psychiatric disorders among women with postpartum psychosis. Nord J Psychiatry 2013;67:53-58. Background: The relapse rate for psychiatric disorders after postpartum psychosis is high. Apart from subsequent puerperal periods, previous studies have not examined when relapses in psychiatric disorders occur. In addition, little is known about the impact of certain individual factors on the risk of non-puerperal readmission among women with previous postpartum psychosis. Aims: The first aim was to examine the association between non-puerperal readmission due to psychiatric disorders and years of follow-up (in total, 30 years) in women with postpartum psychosis. The second aim was to examine the impact of age, type of psychosis, previous hospitalization for psychiatric disorders and level of education on the risk of non-puerperal readmission due to psychiatric disorders. Methods: All Swedish women aged 20-44 with postpartum psychosis (n = 3140) were followed between 1975 and 2004 for non-puerperal readmission due to psychiatric disorders. A Cox frailty regression model was used to estimate hazard ratios for non-puerperal readmission. Results: The risk of non-puerperal readmission, although gradually decreasing with time, remained high many years after the postpartum psychosis. The risk of non-puerperal readmission was significantly higher among women with schizophrenia, lower levels of education and previous psychiatric hospitalization. Conclusions: Postpartum psychosis is often part of a lifelong recurrent psychiatric disorder. Women with schizophrenia, lower levels of education and hospitalization due to a psychiatric disorder prior to postpartum psychosis have a higher risk of non-puerperal readmission. Clinical implications: The findings constitute important knowledge for all healthcare workers encountering women with a previous postpartum psychosis.
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| 8. |
- Nixon Andréasson, Anna, et al.
(författare)
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Associations between leptin and self-rated health in men and women
- 2010
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Ingår i: Gender Medicine. - : Elsevier BV. - 1550-8579 .- 1878-7398. ; 7:3, s. 261-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As an important mediator by which the brain receives information about the body's energy state, leptin may be associated with subjectively perceived health. OBJECTIVE: The main aim of the present study was to investigate concurrent and prospective associations between leptin and self-rated health (SRH), a strong predictor of morbidity and mortality, in a random population sample. An additional aim was to examine whether sick leave was associated with leptin and poor SRH. METHODS: In a prospective, population-based cohort study in Sweden, men and women underwent a medical examination in 1998, at which time blood was drawn and participants were asked to respond to a questionnaire concerning demographics, health behavior, and psychosocial factors. In 2000, the participants responded to a second questionnaire sent by postal mail. Spearman rank correlations were used to investigate the relationships between leptin, SRH, sick leave, and background variables. Partial Spearman coefficients were then calculated to investigate the patterns of association between leptin, SRH, and sick leave independent of age, body mass index (BMI), presence of diagnosis, and testosterone or estradiol. RESULTS: A total of 98 men and 104 women, aged 23 to 76 years, and 91 men and 96 women at follow-up, participated in the study. In men, relatively higher levels of leptin were prospectively associated with relatively worse SRH (rho = 0.20; P = 0.05), but the relationship was not significant in the cross-sectional analysis (rho = 0.18; P = 0.07). This association was not found in women. When controlling for age, BMI, presence of diagnosis, and testosterone, higher levels of leptin were associated with poor SRH in men in cross-sectional analysis (rho = 0.27; P < 0.01) but not prospectively. In women, leptin was not associated with SRH in cross-sectional analysis, but relatively higher levels were prospectively associated with better SRH when adjusted for background factors and estradiol (rho = -0.26; P < 0.05). SRH was independently associated with future sick leave in both men (rho = 0.34; P < 0.01) and women (rho = 0.30; P < 0.05), whereas no association between leptin and future sick leave was found. CONCLUSIONS: Contrasting associations were found between men and women in the relationship between leptin and SRH. Based on the finding that higher leptin levels were associated with better SRH in women than in men, along with corroboration from recent studies, we propose that leptin may serve different psychobiological functions in men than in women.
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| 9. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 10. |
- Sundquist, Kristina, et al.
(författare)
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Elucidating causal effects of type 2 diabetes on ischemic heart disease from observational data on middle-aged Swedish women : a triangular analytical approach
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The association between type 2 diabetes (T2D) and ischemic heart disease (IHD) is well established but the potential causal association needs further studying. In an attempt to elucidate the causal effect of T2D on IHD, we used three different analytical approaches in two different datasets. A well-defined cohort of 6047 women aged 50–59 years were included at baseline (1995 to 2000) and followed until 2015 for IHD. The median follow-up was 16.3 years. We used a Marginal Structural Cox model (MSM Cox) to account for time-varying exposure (time at onset of T2D) and for ten confounders (using inverse probability weighting, IPW). We also compared the MSM-Cox models with traditional Cox regression modelling in the cohort. Finally, we analyzed information on individuals from Swedish population-based registers with national coverage in a comprehensive co-relative design and extrapolated the results to MZ twins. The Hazard Ratio (HR) for IHD in relation to T2D at baseline and T2D occurring during the follow-up in the MSM Cox model weighted by IPW (based on the ten included confounders) was 1.43 (95% confidence interval [CI] 1.07–1.92). The corresponding HR from the traditional Cox regression model was of similar effect size. The average extrapolated MZ twin estimate from our co-relative model was 1.61 (95% CI 1.48–1.86). Our findings, based on a triangular approach, support the existence of a causal association between T2D and IHD and that preventive long-term measures in order to avoid or postpone IHD should include monitoring and treatment of both the T2D itself as well as other cardiovascular risk factors.
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