| 1. |
- Klajic, Jovana, et al.
(författare)
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Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 456-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression. Methods: Quantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV. Results: Significant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival. Conclusions: In the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above.
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| 2. |
- Krvavac, Sanja, et al.
(författare)
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Patients Who Die by Suicide : A Study of Treatment Patterns and Patient Safety Incidents in Norway
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:17
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Tidskriftsartikel (refereegranskat)abstract
- Underlying patterns and factors behind suicides of patients in treatment are still unclear and there is a pressing need for more studies to address this knowledge gap. We analysed 278 cases of suicide reported to The Norwegian System of Patient Injury Compensation, drawing on anonymised data, i.e., age group, gender, diagnostic category, type of treatment provided, inpatient vs. outpatient status, type of treatment facility, and expert assessments of medical errors. The data originated from compensation claim forms, expert assessments, and medical records. Chi-square tests for independence, multinominal logistic regression, and Bayes factors for independence were used to analyse whether the age group, gender, diagnostic category, inpatient/outpatient status, type of institution, and type of treatment received by patients that had died by suicide were associated with different types of medical errors. Patients who received medication tended to be proportionally more exposed to an insufficient level of observation. Those who received medication and psychotherapy tended to be proportionally more exposed to inadequate treatment, including inadequate medication. Inpatients were more likely to be exposed to inappropriate diagnostics and inadequate treatment and follow up while outpatients to insufficient level of observation and inadequate suicide risk assessment. We conclude that the patients who had received medication as their main treatment tended to have been insufficiently observed, while patients who had received psychotherapy and medication tended to have been provided insufficient treatment, including inadequate medication. These observations may be used as learning points for the suicide prevention of patients in treatment in Norwegian psychiatric services.
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| 3. |
- Muggerud, Aslaug Aa, et al.
(författare)
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Frequent aberrant DNA methylation of ABCB1, FOXC1, PPP2R2B and PTEN in ductal carcinoma in situ and early invasive breast cancer
- 2010
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:1, s. R3-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of the breast that is frequently detected by mammography and subsequently removed by surgery. However, it is estimated that about half of the detected lesions would never have progressed into invasive cancer. Identifying DCIS and invasive cancer specific epigenetic lesions and understanding how these epigenetic changes are involved in triggering tumour progression is important for a better understanding of which lesions are at risk of becoming invasive. METHODS: Quantitative DNA methylation analysis of ABCB1, CDKN2A/p16INK4a, ESR1, FOXC1, GSTP1, IGF2, MGMT, MLH1, PPP2R2B, PTEN and RASSF1A was performed by pyrosequencing in a series of 27 pure DCIS, 28 small invasive ductal carcinomas (IDCs), 34 IDCs with a DCIS component and 5 normal breast tissue samples. FOXC1, ABCB1, PPP2R2B and PTEN were analyzed in 23 additional normal breast tissue samples. Real-Time PCR expression analysis was performed for FOXC1. RESULTS: Aberrant DNA methylation was observed in all three diagnosis groups for the following genes: ABCB1, FOXC1, GSTP1, MGMT, MLH1, PPP2R2B, PTEN and RASSF1A. For most of these genes, methylation was already present at the DCIS level with the same frequency as within IDCs. For FOXC1 significant differences in methylation levels were observed between normal breast tissue and invasive tumours (P < 0.001). The average DNA methylation levels were significantly higher in the pure IDCs and IDCs with DCIS compared to pure DCIS (P = 0.007 and P = 0.001, respectively). Real-time PCR analysis of FOXC1 expression from 25 DCIS, 23 IDCs and 28 normal tissue samples showed lower gene expression levels of FOXC1 in both methylated and unmethylated tumours compared to normal tissue (P < 0.001). DNA methylation levels of FOXC1, GSTP1, ABCB1 and RASSF1A were higher in oestrogen receptor (ER) positive vs. ER negative tumours; whereas methylation levels of FOXC1, ABCB1, PPP2R2B and PTEN were lower in tumours with a TP53 mutation. CONCLUSIONS: Quantitative methylation analysis identified ABCB1, FOXC1, PPP2R2B and PTEN as novel genes to be methylated in DCIS. In particular, FOXC1 showed a significant increase in the methylation frequency in invasive tumours. Low FOXC1 gene expression in both methylated and unmethylated DCIS and IDCs indicates that the loss of its expression is an early event during breast cancer progression.
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| 4. |
- Tønnesen, Hanne, et al.
(författare)
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Handling Clinical Health Promotion in the HPH DATA MODEL: Basic Documentation of Health Determinants in Medical Records of tobacco, malnutrition, overweight, physical inactivity & alcohol
- 2012
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Ingår i: Clinical Health Promotion. - 2226-5864. ; 2:1, s. 5-11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundClinical Health Promotion activities contribute to the reduction of disease and treatment, and improve outcomes and prognosis. Accordingly, major health determinants such as smoking, physical inactivity, risk of malnutrition, overweight and hazardous drinking should be easily identified in the medical records. To that end, this study evaluates a simple 9 question health documentation model (HPH DATA Model) to be used in the medical records of patients in need of health promotion. MethodsThe multi-national study took place in 78 pilot centres from 12 nations / regions. First, the HPH DATA Model was pilot tested by clinical specialists in a standardised manner for control under international conditions (A). Then it was tested under local conditions (B). After gaining familiarity with the model, the clinical specialists evaluated whether the model was understandable, applicable and sufficient (C). They were also invited to give comments. ResultsThe response rate was 87-100%; the missing data among responders were 0 - 2.6%. The inter-rater agreement in documenting the 5 risk factors using the HPH DATA Model was substantial to nearly perfect across the pilot centres at International Conditions (A); Kappa value 0.85 (0.65 - 0.99). The clinical specialists categorized 66% (29 - 94%) of the patients from their own clinical practice regarding the need for health promotion (B). Except for waist measure-ments, the clinical specialists found the model understandable, applicable and sufficient. It was also determined that the clinical specialists were in need of a more comprehensive definition of the term “severe illness” (C).ConclusionsThe simple HPH DATA Model for systematic registration of 5 significant health determinants was found to be understandable, applicable and sufficient in different clinical settings.
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