Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495–45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen receptor-positive (ER+) breast cancer (per-g allele OR ER+ = 1.15; 95% CI 1.13–1.18; p = 8.35 × 10−30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER−) breast cancer (lead SNP rs6864776: per-a allele OR ER− = 1.10; 95% CI 1.05–1.14; p conditional = 1.44 × 10−12), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09–1.15; p conditional = 1.12 × 10−05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis

Predictive Risk Factors and Occupational Impact of Self-Perceived Voice Problems in Preschool-Kindergarten versus First- to Sixth-Grade Teachers

Aim: The aim of this investigation was to complete a further analysis of existing data to compare risk factors of voice problems as well as create a hierarchical ranking of risk factors in preschool-kindergarten and 1st- to 6th-grade teachers in order to develop a voice hygiene program and prioritize its goals for each group of teachers. Methods: An online survey was completed by 148 preschool-kindergarten and 301 1st- to 6th-grade public school teachers. Participants were divided into four groups, preschool-kindergarten and 1st- to 6th-grade teachers with no self-perceived voice disorders and preschool-kindergarten and 1st- to 6th-grade teachers with self-perceived voice disorders. A χ2 test and a multivariate logistic regression model were used to examine the differences in answers between the preschool-kindergarten teachers with and without voice disorders and the 1st- to 6th-grade teachers with and without voice disorders and to identify the most important predictors. Results: The significant predictors for preschool-kindergarten teachers are frequently or sometimes continuing to talk after a breath cycle and being exposed to an excessive or a lot of noise generated in the classroom. The significant predictors for 1st- to 6th-grade teachers include having short breaks between classes and continuing to talk frequently after a breath cycle. Conclusions: Job-related risk factors in preschool-kindergarten and in 1st- to 6th-grade teachers may vary. Therefore, a preventative vocal hygiene education program specifically tailored for each population of teachers is suggested

Risk Factors for Voice Disorders in Undergraduate Speech Language Pathology Students

Objectives: The aim of this research study is to determine the risk factors for voice disorders in SLP students in order to help us develop specific goals for a vocal hygiene education program specifically for SLP students. Methods: An online questionnaire was completed by 121 undergraduate SLP students. Participants were divided into two groups, students with no self-perceived voice disorders (NVD group) and students with self-perceived voice disorders (VD group). The Fisher Exact test (FET) was used to explore the differences in responses for each voice risk factor and the academic and occupational consequences between students with and without self-perceived voice disorders. Results: Students in the VD group were more likely to experience vocal fold problems, hearing problems and throat clearing than in the NVD group. More students in the VD group reported to “sometimes’ and “often” take medications that impact their voice, hear a “moderate” amount of noise generated from the passage of planes and the road and hear a “moderate” and “large” amount of noise generated within and outside the building than in the NVD group. Moreover, students in the VD group were more likely to limit their ability to perform certain tasks at school (eg, participating in lectures) and clinical practicum (eg, administering therapy sessions) and reduce their interactions annually due to voice problems. Conclusions: Health, voice use, lifestyle, and environmental factors are risk factors for voice disorders that were presented more frequently in SLP students with self-perceived voice disorders

Risk factors for voice disorders in public school teachers in Cyprus

Aims: The purpose of this study was to investigate risk factors for self-perceived voice disorders in teachers in Cyprus in order to determine the necessity for a preventative vocal hygiene education program which could improve their work performance. Methods: An online questionnaire was completed by 449 teachers. The questionnaire extracted data regarding risk factors that may contribute to the development of voice disorders, occupational consequences of voice disorders and vocal hygiene education, as well as, a self-perceived severity of a participant's voice problem. Subjects were split into two groups, teachers with Voice Disorder Index (VDI)≤7 and teachers with VDI>7. The chi-squared test was used to explore the differences in responses for each voice risk factor, occupational consequence and vocal hygiene education between the two groups. Results: Teachers in the VDI> 7 group were more likely to frequently experience nasal allergies and respiratory infections, coughing, throat clearing, stress and yelling, have shorter breaks between classes, use loud voice, use their voice to discipline students, teach above students talking, etc. than teachers in the VDI≤7 group. Moreover, teachers in the VDI>7 group were more likely to limit their ability to perform certain tasks at work and reduce their activities or interactions "3-5 or more days"annually due to voice problems. Conclusions. Health, voice use, lifestyle, and environmental factors may play a part in the development of voice disorders in teachers and have an impact on their job. Therefore, a preventative vocal hygiene education program is suggested

Correlation Between a Self-Voice Assessment and Objective-Voice Evaluation Outcomes in Speech Language Pathology Students

Aim The aims of this study is to explore the correlation between the Voice Disorder Index (VDI) score and acoustic and phonatory respiratory voice parameters in speech language pathology (SLP) students with and without self-perceived voice disorders. Methods The Voice Disorder Index (VDI) and the Lingwaves 3 “Voice Protocol” were administered to each participant in order to assess his/her self-perceived severity of his/her voice problem, as well as, acoustic and phonatory respiratory measurements. The correlation coefficients were used to evaluate and quantify the degree of a linear relationship between VDI scores and acoustic and phonatory respiratory voice measures in students with and without self-perceived voice disorders. Results Relatively strong, strong and strong positive correlations were revealed when comparing the VDI physical subscale with the Dysphonia Severity Index (r(11) = 0.56, P = 0.048), mean loudness when reading in English (r(11) = 0.70, P = 0.008) and mean loudness when reading in Greek (r(11) =0.69, P = 0.009) respectively. Conclusions SLP students may be more aware of the impact of their laryngeal discomfort and voice output characteristics on their daily activities that can predict certain acoustic parameters than the emotional and functional impact on their daily activities

A new approach for the production of a hydrogen-rich gas from biomas - an absorption enhanced reforming process (AER-GAS)

3rd six-month report,1 August 2003, 4th six-month report, 31 December 2003The aim of the proposed project is to convert biomass in an AER (Absorption Enhanced Reforming) process to obtain a gas containing > 80 Vol.% hydrogen with tar content < 300 mg/m3 . A CO2-absorbent in the reactor bed not only removes CO2 from the product gas but also shifts the chemical equilibrium towards H2, away from CO, hydrocarbons, soot and tar. Consequently the number of required process units is minimised, which reduces cost and increases energetic efficiency. Different catalytic absorbent materials will be investigated. The combustion of charcoal formed in AER gasification provides the heat required for the regeneration of the absorbent. Using existing gasifiers and the experience with AER hydrocarbon reforming will minimise technical risk. The produced hydrogen-rich gas can be used directly or - after gas conditioning - in fuel cells and for synfuel production

The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells

Cancer cell characteristics may play a pivotal role in the response to therapy by activating or deactivating different molecular pathways. In the present study, we investigated the implication of breast cancer cell features, such as HER2 and p53 in the activation of telomerase upon exposure to ionizing radiation. Telomerase is among the most important cancer biomarkers, conferring to tumor cells unlimited proliferative capacity, increased survival potential and resistance to several types of cellular stress. We investigated possible mechanisms regulating telomerase in six irradiated breast cancer cell lines (MCF-7, MCF-7/HER2, MDA-MB-231, SK-BR-3, BT-474 and HBL-100) differing in their HER2, p53 and ER alpha status. hTERT mRNA expression was evaluated by real-time PCR and telomerase activity by the TRAP assay. HER2, c-myc, p53 and p21 protein levels were evaluated by Western blotting. Silencing of hTERT and HER2 was achieved by small interfering RNA technology. Chromatin immunoprecipitation was used to evaluate H3 histone acetylation status, as well as myc/mad/max and p53 transcription factors interaction with the hTERT promoter. Our results showed for the first time, that only HER2-positive cells, independently of their p53 status, upregulated hTERT/telomerase, while knockdown of hTERT increased radio-sensitivity. Knockdown of HER2 also led to increased radio-sensitivity and downregulation of hTERT/ telomerase. We also demonstrated that c-myc and mad1 regulate hTERT expression in all irradiated breast cancer cells. We conclude, for the first time, that HER2 phenotype upregulates hTERT through c-myc activation and confers radio-resistance to breast cancer cells