48 research outputs found

    Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma

    Get PDF
    BACKGROUND: Chromosomal Comparative Genomic Hybridization (CGH) has been applied to all stages of cervical carcinoma progression, defining a specific pattern of chromosomal imbalances in this tumor. However, given its limited spatial resolution, chromosomal CGH has offered only general information regarding the possible genetic targets of DNA copy number changes. METHODS: In order to further define specific DNA copy number changes in cervical cancer, we analyzed 20 cervical samples (3 pre-malignant lesions, 10 invasive tumors, and 7 cell lines), using the GenoSensor microarray CGH system to define particular genetic targets that suffer copy number changes. RESULTS: The most common DNA gains detected by array CGH in the invasive samples were located at the RBP1-RBP2 (3q21-q22) genes, the sub-telomeric clone C84C11/T3 (5ptel), D5S23 (5p15.2) and the DAB2 gene (5p13) in 58.8% of the samples. The most common losses were found at the FHIT gene (3p14.2) in 47% of the samples, followed by deletions at D8S504 (8p23.3), CTDP1-SHGC- 145820 (18qtel), KIT (4q11-q12), D1S427-FAF1 (1p32.3), D9S325 (9qtel), EIF4E (eukaryotic translation initiation factor 4E, 4q24), RB1 (13q14), and DXS7132 (Xq12) present in 5/17 (29.4%) of the samples. CONCLUSION: Our results confirm the presence of a specific pattern of chromosomal imbalances in cervical carcinoma and define specific targets that are suffering DNA copy number changes in this neoplasm

    Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

    Get PDF
    The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional 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 BC risk for BRCA2 carriers (per-allele Hazard Ratio (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 BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values: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 BC risk for mutation carriers. Based on the joint genotype distribution of the seven 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 BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers

    Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    Get PDF
    Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers

    Promoting mental health literacy in schools

    No full text
    Fretian A, Kirchhoff S, Graf P, Bauer U. Promoting mental health literacy in schools. In: 16th World Congress on Public Health 2020. Public Health for the future of humanity: analysis, advocacy and action. European Journal of Public Health. Vol 30. Oxford: Oxford Univ Press; 2020: V103

    Evaluation of a school-based intervention to promote mental health literacy. Preliminary results

    No full text
    Kirchhoff S, Fretian A, Graf P, Bauer U. Evaluation of a school-based intervention to promote mental health literacy. Preliminary results. European Journal of Public Health . 2021;31(Suppl. 3):56.Background Mental illness is one of the leading causes of ill-health and disability. The current COVID-19 pandemic poses an additional challenge on mental health, e.g., through increased levels of anxiety, depression and fears about the future. As most mental illnesses develop before the age of 25, young people are a critical target group for prevention. Mental health literacy (MHL) is considered to be a key determinant of positive mental health, thus, being crucial for mental health promotion and dealing with the aftermath of the pandemic. This project aims at (i) adapting an evidence-based MHL curriculum for German schools, as school-based interventions are suitable in reaching most young people, and (ii) evaluating its acceptance and effectiveness regarding MHL and stigmatizing attitudes. Methods An interdisciplinary team including representatives from self-help groups for mental health translated and adapted the Canadian “TeenMentalHealth” curriculum for German schools. The evaluation design includes a pre, post, follow-up assessment of MHL, stigmatizing attitudes, and help-seeking efficacy. Results For better applicability of the curriculum, the original program was shortened, while keeping its core contents such as knowledge and myths around mental health and illness. Written and digital material was developed and distributed to teachers, which were trained to deliver the intervention. Preliminary results show high acceptability, a significant increase in MHL and a decrease in stigmatizing attitudes, while help-seeking efficacy remained unchanged. Conclusions An MHL intervention was successfully adapted for the German school setting. While evaluation is ongoing, first results indicate its effectiveness in promoting MHL among students, decreasing stigmatizing attitudes and high acceptability, even during the times of the pandemic. Further evaluation is necessary to confirm the preliminary findings and to gain insight into the missing effect on help-seeking efficacy

    The Long-Term Effectiveness of Interventions Addressing Mental Health Literacy and Stigma of Mental Illness in Children and Adolescents: Systematic Review and Meta-Analysis

    No full text
    Fretian A, Graf P, Kirchhoff S, et al. The Long-Term Effectiveness of Interventions Addressing Mental Health Literacy and Stigma of Mental Illness in Children and Adolescents: Systematic Review and Meta-Analysis. International Journal of Public Health. 2021;66: 1604072.Objectives:This study aims to provide a systematic review and meta-analysis of the literature on the long-term effects of interventions addressing children’s and adolescents’ mental health literacy and/or stigmatizing attitudes.Methods:Articles in English or German published between January 1997 and May 2020 were retrieved from five databases, leading to a total of 4,375 original articles identified.Results:25 studies were included after applying exclusion criteria, 13 of which were eligible for meta-analysis. The overall average of the follow-up period was about 5 months. Long-term improvements were sustained for mental health literacy, d = 0.48, 95% CI = (0.34, 0.62), as well as for stigmatizing attitudes, d = 0.30, 95% CI = (0.24, 0.36), and social distance, d = 0.16, 95% CI = (0.03, 0.29). The combination of educational and contact components within interventions led to worse results for mental health literacy, but not stigmatizing attitudes or social distance.Conclusion:Interventions targeting children and adolescents generally have a brief follow-up period of an average of 5 months. They show a stable improvement in mental health literacy, but are to a lesser degree able to destigmatize mental illness or improve social distance

    The Value of Peer Mentoring Networks for Developing Leaders and Inspiring Change

    No full text
    A peer-mentoring network, funded by the National Science Foundation ADVANCE program, profoundly impacted the career trajectory of five women chemistry faculty at predominantly undergraduate institutions. By providing each other support, encouragement, information, and accountability, we advanced our careers, became leaders in our own right, and implemented change at our institutions. To extend this benefit to more women STEM faculty, we have developed and implemented a model to support 74 faculty and administrators representing 51 institutions across the country
    corecore