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Sökning: WFRF:(Duran M) > Linköpings universitet

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  • Antoniou, A. C., et al. (författare)
  • Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
  • 2010
  • Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
  • Tidskriftsartikel (refereegranskat)abstract
    • The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
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  • Armandi, Angelo, et al. (författare)
  • Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease
  • 2024
  • Ingår i: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 mu g/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 mu g/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 mu g/L and 272 mu g/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices>0.71) and overall mortality (C-indices>0.65). Conclusions This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.
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  • Duran, J., et al. (författare)
  • Different Cerrado Ecotypes Show Contrasting Soil Microbial Properties, Functioning Rates, and Sensitivity to Changing Water Regimes
  • 2023
  • Ingår i: Ecosystems. - : SPRINGER. - 1432-9840 .- 1435-0629. ; 26, s. 1381-1395
  • Tidskriftsartikel (refereegranskat)abstract
    • Soil moisture is among the most important factors regulating soil biodiversity and functioning. Models forecast changes in the precipitation regime in many areas of the planet, but how these changes will influence soil functioning, and how biotic drivers modulate such effects, is far from being understood. We evaluated the responses of C and N fluxes, and soil microbial properties to different soil water regimes in soils from the main three ecotypes of the worlds largest and most diverse tropical savanna. Further, we explored the direct and indirect effects of changes in the ecotype and soil water regimes on these key soil processes. Soils from the woodland savanna showed a better nutritional status than the other ecotypes, as well as higher potential N cycling rates, N2O emissions, and soil bacterial abundance but lower bacterial richness, whereas potential CO2 emissions and CH4 uptake peaked in the intermediate savanna. The ecotype also modulated the effects of changes in the soil water regime on nutrient cycling, greenhouse gas fluxes, and soil bacterial properties, with more intense responses in the intermediate savanna. Further, we highlight the existence of multiple contrasting direct and indirect (via soil microbes and abiotic properties) effects of an intensification of the precipitation regime on soil C- and N-related processes. Our results confirm that ecotype is a fundamental driver of soil properties and functioning in the Cerrado and that it can determine the responses of key soil processes to changes in the soil water regime.
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  • Loizou, L., et al. (författare)
  • Radiological assessment of local resectability status in patients with pancreatic cancer: Interreader agreement and reader performance in two different classification systems
  • 2018
  • Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 106, s. 69-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess the interreader agreement and reader performance in the evaluation of patients with pancreatic cancer (PC) in two classification systems of local resectability status prior to initiation of therapy, namely the National Comprehensive Cancer Network (NCCN) and Karolinska classification system (KCS). Methods: In this ethics review board-approved retrospective study, six radiologists independently evaluated pancreatic CT-examinations of 30 patients randomly selected from a tertiary referral centre's multidisciplinary tumour board database. Based on well-defined criteria of tumour-vessel relationship, each patient was assigned to one of three NCCN and six KCS categories. We assessed the intraclass correlation coefficient (ICC) and compared the percentages of correct tumour classification of the six readers in both systems (Chi-square test; a P-value < 0.05 was considered significant). The standard of reference was a consensus evaluation of CT-examinations by three readers not involved in the image analysis. Results: The ICC for NCCN and KCS was 0.82 and 0.84, respectively (very strong agreement). The percentages of correct tumour classification at NCCN and KCS were 53-83% and 30-57%, respectively, with no statistically significant differences in the overall reader comparison per classification system. In pair-wise comparison between readers for NCCN/KCS, there were statistically significant differences between reader 5 vs. readers 4 (P = 0.012) and 3 (P = 0.045)/ reader 5 vs. reader 4 (P = 0.037). Conclusion: Interreader agreement in both PC classification systems is very strong. NCCN may be advantageous in terms of reader performance compared to KCS.
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