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1.
  • Adams, Charleen, et al. (författare)
  • Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
  • 2019
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:1, s. 208-216
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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2.
  • Aglago, Elom K., et al. (författare)
  • A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
  • 2023
  • Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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3.
  • Ahmed, Hanna N., et al. (författare)
  • Coffee consumption and risk of heart failure in men : An analysis from the Cohort of Swedish Men
  • 2009
  • Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 158:4, s. 667-672
  • Tidskriftsartikel (refereegranskat)abstract
    • Background A previous study found that consuming 5 or more cups of coffee per day was associated with increased incidence of heart failure (HF). We sought to evaluate this association in a larger population. Methods We measured coffee consumption using food frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HE They were observed for HF hospitalization or mortality from January 1, 1998, until December 3 1, 2006, using record linkage to the Swedish inpatient and cause of death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CIs). Results For 9 years of follow-up, 784 men experienced an HF event. Compared to men who drank! l cup of coffee per day (unadjusted rate 29.9 HF events/ 10,000 person-years), RR were 0.87 (95% CI 0.69-1.11, unadjusted rate 29.2/10,000 person-years) for 2 cups/d, 0.89 (95% CI 0.70-1.14, unadjusted rate 25.1/10,000 person-years) for 3 cups/d, 0.89 (95% CI 0.69-1.15, unadjusted rate 25.0/10,000 person-years) for 4 cups/d, and 0.89 (95% CI 0.69-1.15, unadjusted rate 18.1/10,000 person-years) for >= 5 cups/d (P for trend in RR = .61). Conclusions This study did not support the hypothesis that high coffee consumption is associated with increased rates of HF hospitalization or mortality. (Am Heart J 2009;158:667-72.)
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4.
  • Akesson, Agneta, et al. (författare)
  • Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women
  • 2007
  • Ingår i: Archives of Internal Medicine. - Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-17177 Stockholm, Sweden. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. : AMER MEDICAL ASSOC. - 0003-9926 .- 1538-3679. ; 167:19, s. 2122-2127
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Limited data are available on the benefit of combining healthy dietary and lifestyle behaviors in the prevention of myocardial infarction (MI) in women. Methods: We used factor analysis to identify a lowrisk behavior - based dietary pattern in 24 444 postmenopausal women from the population- based prospective Swedish Mammography Cohort who were free of diagnosed cancer, cardiovascular disease, and diabetes mellitus at baseline (September 15, 1997). We also defined 3 low- risk lifestyle factors: nonsmoking, waist- hip ratio less than the 75th percentile (< 0.85), and being physically active (at least 40 minutes of daily walking or bicycling and 1 hour of weekly exercise). Results: During 6.2 years (151 434 person- years) of followup, we ascertained 308 cases of primary MI. Two major identified dietary patterns, "healthy" and "alcohol," were significantly associated with decreased risk of MI. The low- risk diet (high scores for the healthy dietary pattern) characterized by a high intake of vegetables, fruit, whole grains, fish, and legumes, in combination with moderate alcohol consumption (>= 5 g of alcohol per day), along with the 3 low-risk lifestyle behaviors, was associated with 92% decreased risk (95% confidence interval, 72%- 98%) compared with findings in women without any low-risk diet and lifestyle factors. This combination of healthy behaviors, present in 5%, may prevent 77% of MIs in the study population. Conclusion: Most MIs in women may be preventable by consuming a healthy diet and moderate amounts of alcohol, being physically active, not smoking, and maintaining a healthy weight.
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5.
  • Akesson, Agneta, et al. (författare)
  • Dietary exposure to polychlorinated biphenyls and risk of heart failure - A population-based prospective cohort study
  • 2019
  • Ingår i: Environment International. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0160-4120 .- 1873-6750. ; 126, s. 1-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Beneficial effects of fish consumption on heart failure (HF) may be modified by contaminants in fish. Polychlorinated biphenyls (PCBs) are of particular concern as they have been associated with well-established risk factors of HF, but current data are limited. Objectives: We aimed to assess the association between dietary PCB exposure and risk of HF, accounting for dietary intake of long-chain omega-3 fish fatty acids. Design: We used the prospective population-based research structure SIMPLER (previously the Swedish Mammography Cohort and Cohort of Swedish Men) comprising 32,952 women and 36,546 men, free from cancer, cardiovascular disease and diabetes at baseline in 1997. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)] were obtained via a food frequency questionnaire at baseline. Incident cases of HF were ascertained through register linkage. Results: During an average of 12 years of follow-up, we ascertained 2736 and 3128 incident cases of HF in women and men, respectively. In multivariable-adjusted models, mutually adjusted for PCBs and EPA-DHA, the relative risk (RR) for dietary PCB exposure was 1.48 (95% CI 1.12-1.96) in women and 1.42 (95% CI 1.08-1.86) in men, comparing extreme quintiles. Corresponding RRs for EPA-DHA intake were 0.71 (95% CI 0.54-0.93) and 0.82 (95% CI 0.63-1.07), respectively. Conclusions: Dietary exposure to PCBs was associated with an increased risk of HF in both women and men. EPA-DHA intake was associated with a lower risk of HF in women, with a similar tendency in men.
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6.
  • Akesson, Agneta, et al. (författare)
  • Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence : A population-based prospective cohort study
  • 2008
  • Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 68:15, s. 6435-6441
  • Tidskriftsartikel (refereegranskat)abstract
    • Environmental pollutants mimicking the effects of estrogen are suggested to contribute to the high incidence of hormone-related cancers, but supporting data are sparse. A potent estrogen-like activity of the pollutant cadmium, mediated via the estrogen receptor-alpha, has been shown in vivo. We prospectively examined the association between cadmium exposure and incidence of postmenopausal endometrial cancer. The Swedish Mammography Cohort is a population-based prospective cohort of 30,210 postmenopausal women free of cancer diagnose at baseline (1987) and who completed a food frequency questionnaire at baseline and in 1997. We estimated the dietary cadmium intake based on the questionnaire data and the cadmium content in all foods. During 16.0 years (484,274 person-years) of follow-up between the baseline and mid-2006, we ascertained 378 incident cases of endometrioid adenocarcinoma. The average estimated dietary cadmium intake was 15 mu g/day (80% from cereals and vegetables). Cadmium intake was statistically significantly associated with increased risk of endometrial cancer in all women; the multivariate relative risk (1111) was 1.39 [95% confidence interval (CI), 1.04-1.86; P-trend = 0.019], comparing highest tertile versus lowest. Among never-smoking women with body mass index (BMI) of <27 kg/m(2), the RR was 1.86 (95% CI, 1.13-3.08; P-trend = 0.009). We observed a 2.9-fold increased risk (95% CI, 1.05-7.79) associated with long-term cadmium intake consistently above the median at both baseline 1987 and in 1997 in never-smoking women with low bioavailable estrogen (BMI of <27 kg/m(2) and nonusers of postmenopausal hormones). Our results support the hypothesis that cadmium may exert estrogenic effects and thereby increase the risk of hormone-related cancers.
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7.
  • Akesson, Agneta, et al. (författare)
  • Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men A Population-Based Prospective Cohort Study
  • 2014
  • Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 64:13, s. 1299-1306
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Adherence to a combination of healthy dietary and lifestyle practices may have an impressive impact on the primary prevention of myocardial infarction (MI). OBJECTIVES The aim of this study was to examine the benefit of combined low-risk diet and healthy lifestyle practices on the incidence of MI in men. METHODS The population-based, prospective cohort of Swedish men comprised 45-to 79-year-old men who completed a detailed questionnaire on diet and lifestyle at baseline in 1997. In total, 20,721 men with no history of cancer, cardiovascular disease, diabetes, hypertension, or high cholesterol levels were followed through 2009. Low-risk behavior included 5 factors: a healthy diet (top quintile of Recommended Food Score), moderate alcohol consumption (10 to 30 g/day), no smoking, being physically active (walking/bicycling >= 40 min/day and exercising >= 1 h/week), and having no abdominal adiposity (waist circumference <95 cm). RESULTS During 11 years of follow-up, we ascertained 1,361 incident cases of MI. The low-risk dietary choice together with moderate alcohol consumption was associated with a relative risk of 0.65 (95% confidence interval [CI]: 0.48 to 0.87) compared with men having 0 of 5 low-risk factors. Men having all 5 low-risk factors compared with those with 0 low-risk factors had a relative risk of 0.14 (95% CI: 0.04 to 0.43). This combination of healthy behaviors, present in 1% of the men, could prevent 79% (95% CI: 34% to 93%) of the MI events on the basis of the study population. CONCLUSIONS Almost 4 of 5 MIs in men may be preventable with a combined low-risk behavior. (C) 2014 by the American College of Cardiology Foundation.
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8.
  • Almgren, Malin, et al. (författare)
  • Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA
  • 2012
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 7:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings: Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 nondiabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from similar to 7% in 1992-1998 to 15-20% in 2002-2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion: Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.
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9.
  • Amzal, Billy, et al. (författare)
  • Population Toxicokinetic Modeling of Cadmium for Health Risk Assessment
  • 2009
  • Ingår i: Journal of Environmental Health Perspectives. - : US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE. - 0091-6765 .- 1552-9924. ; 117:8, s. 1293-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers. OBJECTIVE: Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata. METHODS: We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellstrom model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans. RESULTS: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability. CONCLUSIONS: Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.
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10.
  • Balder, Helena F, et al. (författare)
  • Common and country-specific dietary patterns in four European cohort studies
  • 2003
  • Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 133:12, s. 4246-51
  • Tidskriftsartikel (refereegranskat)abstract
    • The association between diet and cancer, predominantly investigated univariately, has often been inconsistent, possibly because of the large number of candidate risk factors and their high intercorrelations. Analysis of dietary patterns is expected to give more insight than analysis of single nutrients or foods. This study aimed to develop and apply a common methodological approach to determine dietary patterns in four cohort studies originating in Finland, the Netherlands, Sweden and Italy. Food items on each of the food frequency questionnaires were aggregated into 51 food groups, defined on the basis of their position in the diet pattern and possible relevance to cancer etiology. Exploratory factor analysis was used to analyze dietary patterns. Using a standardized approach, 3-5 stable dietary patterns were identified, explaining 20-29% of total variance in consumption of the food groups. Two dietary patterns, which explained most of the variance, were consistent across the studies. The first pattern was characterized by high consumption of (salad) vegetables, the second by high consumption of pork, processed meat and potatoes. In addition, a few specifically national food patterns were identified. Sensitivity analyses showed that the identified patterns were robust for number of factors extracted, distribution of input variables and energy adjustment. Our findings suggest that some important eating patterns are shared by the four populations under study, whereas other eating patterns are population specific.
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