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Sökning: WFRF:(Szulkin Robert)

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  • Dadaev, Tokhir, et al. (författare)
  • Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.
  • 2018
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
  • Andreasson, Anna Nixon, et al. (författare)
  • Inflammation and positive affect are associated with subjective health in women of the general population
  • 2013
  • Ingår i: Journal of Health Psychology. - 1359-1053 .- 1461-7277. ; 18:3, s. 311-320
  • 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.
  • Bonn, Stephanie E., et al. (författare)
  • Body mass index and weight change in men with prostate cancer : progression and mortality
  • 2014
  • Ingår i: Cancer Causes and Control. - : Springer Netherlands. - 0957-5243 .- 1573-7225. ; 25:8, s. 933-943
  • 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.
  • Kawakami, Naomi, et al. (författare)
  • Differences in neighborhood accessibility to health-related resources: A nationwide comparison between deprived and affluent neighborhoods in Sweden
  • 2011
  • Ingår i: Health and Place. - : Elsevier. - 1873-2054 .- 1353-8292. ; 17:1, s. 132-139
  • 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.
  • Nager, Anna, et al. (författare)
  • High lifelong relapse rate of psychiatric disorders among women with postpartum psychosis
  • 2013
  • Ingår i: Nordic Journal of Psychiatry. - : Informa Healthcare. - 1502-4725. ; 67:1, s. 53-58
  • 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.
  • Nixon Andréasson, Anna, et al. (författare)
  • Associations between leptin and self-rated health in men and women
  • 2010
  • Ingår i: Gender Medicine. - 1550-8579 .- 1878-7398. ; 7:3, s. 261-9
  • 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.
  • Szulkin, Robert, et al. (författare)
  • Prediction of individual genetic risk to prostate cancer using a polygenic score.
  • 2015
  • Ingår i: The Prostate. - 0270-4137 .- 1097-0045. ; 75:13, s. 1467-74
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction.METHODS: We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls.RESULTS: The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk.CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.
  • Szulkin, Robert, et al. (författare)
  • Prostate cancer risk variants are not associated with disease progression.
  • 2012
  • Ingår i: The Prostate. - 1097-0045 .- 0270-4137. ; 72:1, s. 30-39
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Currently used prognostic markers are limited in their ability to accurately predict disease progression among patients with localized prostate cancer. We examined 23 reported prostate cancer susceptibility variants for association with disease progression. METHODS: Disease progression was explored among 4,673 Swedish patients treated for clinically localized prostate cancer between 1997 and 2002. Prostate cancer progression was defined according to primary treatment as a composed event reflecting termination of deferred treatment, biochemical recurrence, local progression, or presence of distant metastasis. Association between single variants, and all variants combined, were performed in Cox regression analysis assuming both log-additive and co-dominant genetic models. RESULTS: Three of the 23 genetic variants explored were nominally associated with prostate cancer progression; rs9364554 (P = 0.041) on chromosome 6q25 and rs10896449 (P = 0.029) on chromosome 11q13 among patients treated with curative intent; and rs4054823 (P = 0.008) on chromosome 17p12 among patients on surveillance. However, none of these associations remained statistically significant after correction for multiple testing. The combined effect of all susceptibility variants was not associated with prostate cancer progression neither among patients receiving treatment with curative intent (P = 0.14) nor among patients on surveillance (P = 0.92). CONCLUSIONS: We observed no evidence for an association between any of 23 established prostate cancer genetic risk variants and disease progression. Accumulating evidence suggests separate genetic components for initiation and progression of prostate cancer. Future studies systematically searching for genetic risk variants associated with prostate cancer progression and prognosis are warranted. Prostate © 2011 Wiley-Liss, Inc.
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