| 1. |
- Davies, John R., et al.
(författare)
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An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study
- 2014
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Ingår i: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 27:2, s. 234-243
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Tidskriftsartikel (refereegranskat)abstract
- An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma-specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.
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| 2. |
- Denisova, Evgeniya, et al.
(författare)
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Frequent DPH3 promoter mutations in skin cancers.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:34, s. 35922-35930
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.
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| 3. |
- Heidenreich, Barbara, et al.
(författare)
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TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.
- 2015
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Ingår i: Oncotarget. - 1949-2553. ; 6:12, s. 10617-10633
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Tidskriftsartikel (refereegranskat)abstract
- In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 - 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.
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| 4. |
- Hosen, Ismail, et al.
(författare)
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Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1621-1629
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the promoter of the telomerase reverse transcriptase (TERT) and fibroblast growth factor receptor 3 (FGFR3) genes constitute the most recurrent somatic alterations in urothelial carcinoma of bladder. In this study, we screened DNA from 327 urothelial bladder carcinomas from well-documented patients, with different stages and grades and known TERT promoter mutational status, for FGFR3 alterations and measured relative telomere length (RTL). Although, the frequency of the TERT promoter mutations was higher than those in FGFR3; however, the alterations at the two loci occurred together more frequently than per chance [Odds ratio (OR)=4.93, 95% CI=2.72-8.92, p<0.0001]. While tumors with TERT promoter and FGFR3 mutations had shorter RTL than those without mutations (p<0.0001), the TERT promoter mutations in conjunction with the common allele of the rs2853669 polymorphism defined sub-group of patients with an observed decreased overall survival (OR=2.15, 95% CI=1.00-4.61) and increased recurrence in patients with TaG1+TaG2 disease categories (OR=3.68, 95%CI=1.12-12.05). The finding of shorter telomeres in tumors with TERT promoter and/or FGFR3 mutations than without mutations implies mechanistic relevance of telomere biology in cancer progression. The observed association with recurrence and survival shows that the TERT promoter mutations can potentially be used as markers to refine selection of patients for different treatments. The overwhelming frequency of the TERT promoter mutations also represents a case for development of an eventual therapeutic target. What's New? The identification of recurrent somatic mutations in bladder cancer opens the door to the development of new prognostic and therapeutic tools. Here, the TERT promoter mutations in conjunction with a common variant, rs2853669, define a subset of patients with increased risk of recurrence and poor survival. Mutations in FGFR3, in contrast, were not independently associated with either disease recurrence or overall survival. Tumors with mutations in FGFR3 or the TERT promoter carried shorter telomeres than those without mutations. The findings highlight the prognostic potential of TERT mutations and reveal a possible etiological role for telomere biology in bladder cancer.
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| 5. |
- Hosen, Ismail, et al.
(författare)
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TERT promoter mutations in clear cell renal cell carcinoma
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:10, s. 2448-2452
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Tidskriftsartikel (refereegranskat)abstract
- We screened promoter region of the telomerase reverse transcriptase (TERT) for activating somatic mutations in 188 tumors from patients with clear cell renal cell carcinoma (ccRCC). Twelve tumors (6.4%) carried a mutation within the core promoter region of the gene. The mutations were less frequent in high grade tumors compared to low grade tumors [odds ratio (OR)=0.15, 95% confidence interval (CI)=0.03-0.72, p=0.02]. Multivariate analysis for cause specific survival showed statistically significant poor outcome in patients with TERT promoter mutations [hazard ratio (HR)=2.90, 95% CI=1.13-7.39, p=0.03]. A common polymorphism (rs2853669) within the locus seemed to act as a modifier of the effect of the mutations on patient survival as the noncarriers of the variant allele with the TERT promoter mutations showed worst survival (HR=3.34, 95% CI=1.24-8.98, p=0.02). We also measured relative telomere length (RTL) in tumors and difference between tumors with and without the TERT promoter mutations was not statistically significant. Similarly, no difference in patient survival based on RTL in tumors was observed. Our study showed a relatively low frequency of TERT promoter mutations in ccRCC. Nevertheless, patients with the mutations, particularly in the absence of the rs2853669 variant showed the worst disease-specific survival. Thus, it is possible that the TERT promoter mutations define a small subset of tumors with an aggressive behavior. What's new? The human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase, a ribonucleoprotein complex that maintains genomic integrity. Activating somatic mutations in the promoter region of the TERT gene have been reported in many cancers. Here, the authors describe new TERT promoter mutations in clear cell renal cell carcinoma. Although present only in a proportion of the tumors, the TERT promoter mutations were independently associated with poor patient survival. The effect was enhanced by a common polymorphism within the core TERT promoter. The TERT promoter mutations may thus define a small subset of tumors with an aggressive behavior.
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| 6. |
- Li, Li, et al.
(författare)
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A network analysis of the Internet Disorder Scale-Short Form (IDS9-SF) : A large-scale cross-cultural study in Iran, Pakistan, and Bangladesh
- 2023
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Ingår i: Current Psychology. - : Springer. - 1046-1310 .- 1936-4733. ; 42, s. 21994-22003
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Tidskriftsartikel (refereegranskat)abstract
- The Internet Disorder Scale-Short Form (IDS9-SF) is a validated instrument assessing internet disorder which modified the internet gaming disorder criteria proposed in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). However, the relationships between the nine items in the IDS9-SF are rarely investigated. The present study used network analysis to investigate the features of the IDS9-SF among three populations in Bangladesh, Iran, and Pakistan. Data were collected (N = 1901; 957 [50.3%] females; 666 [35.0%] Pakistani, 533 [28.1%] Bangladesh, and 702 [36.9%] Iranians) using an online survey platform (e.g., Google Forms). All the participants completed the IDS9-SF. The central-stability-coefficients of the nine IDS9-SF items were 0.71, 0.89, 0.96, 0.98, 0.98, 1.00, 0.67, 0.79, and 0.91, respectively. The node centrality was stable and interpretable in the network. The Network Comparison Test (NCT) showed that the network structure had no significant differences among Pakistani, Bangladeshi, and Iranian participants (p-values = 0.172 to 0.371). Researchers may also use the IDS9-SF to estimate underlying internet addiction for their target participants and further explore and investigate the phenomenon related to internet addiction.
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| 7. |
- Lin, Chung -Ying, et al.
(författare)
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A phubbing scale tested in Bangladesh, Iran, and Pakistan : confirmatory factor, network, and Rasch analyses
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phubbing, a phenomenon of ignoring others in face-to-face conversations due to mobile phone use, can be assessed using a Phubbing Scale (PS). Recently, the PS has been shortened into an eight-item version, the PS-8. However, psychometric properties of the PS-8 among Iranian, Bangladeshi and Pakistani individuals remain understudied, especially using advanced psychometric testing, such as Rasch and network analyses.Methods: Participants residing in Iran, Bangladesh, and Pakistan (n = 1902; 50.4% females; mean age = 26.3 years) completed the PS-8 and the Internet Disorder Scale-Short Form (IDS9-SF) via an online survey. Network analysis was used to examine if PS-8 items were differentiated from IDS9-SF items; confirmatory factor analysis (CFA) was used to examine the factor structure and measurement invariance of the PS-8; Rasch modeling was used to examine the dimensionality of the PS-8 and differential item functioning (DIF).Results: Network analysis showed that PS-8 items were clustered together with a distance to the IDS9-SF items. The CFA results supported a two-factor structure of the PS-8, and the two-factor structure was found to be invariant across countries and women and men. Rasch model results indicated that the two PS-8 subscales were both unidimensional and did not display DIF across countries and gender/sex.Conclusion: The PS-8 is a feasible and robust instrument for healthcare providers, especially mental health professionals, to quickly assess and evaluate individuals’ phubbing behaviors.
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| 8. |
- Pakpour, Amir H., et al.
(författare)
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A population-based nationwide dataset concerning the COVID-19 pandemic and serious psychological consequences in Bangladesh
- 2020
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Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the dataset concerning knowledge, preventive behavior, psychological consequences, and suicidal behavior regarding the COVID-19 pandemic in Bangladesh. Data were collected through an online based cross-sectional survey between April 1 and April 10 in 64 districts at the early stage of the COVID-19 pandemic in Bangladesh. A total of 10,067 participants' data were recruited for analysis. The survey contained items concerning (i) socio-demographic information, (ii) knowledge concerning COVID-19, (iii) behavior towards COVID-19, (iv) lockdown and economic issues, (v) assessment of fear of COVID-19, (vi) assessment of insomnia, (vii) assessment of depression, and (viii) assessment of suicidal ideation. Data were analyzed utilizing SPSS (version 22) and are represented as frequencies and percentages based on responses to the whole survey. Given that the data were collected across the whole nation, government authorities and healthcare policymakers can use the data to develop various models and/or policies regarding preventive strategies and help raise awareness through health education towards COVID-19.
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| 9. |
- Rachakonda, P. Sivaramakrishna, et al.
(författare)
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TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism
- 2013
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:43, s. 17426-17431
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Tidskriftsartikel (refereegranskat)abstract
- The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions - 124 and - 146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18-1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.
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| 10. |
- Simon, Matthias, et al.
(författare)
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TERT promoter mutations: a novel independent prognostic factor in primary glioblastomas.
- 2015
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 17:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Activating somatic mutations in the promoter region of the telomerase reverse transcriptase gene (TERT) have been detected in several cancers. In this study we investigated the TERT promoter mutations and their impact on patient survival in World Health Organization grade IV glioblastoma multiforme (GBM).
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| 11. |
- Sultana, Naznin, et al.
(författare)
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Sleep Problems in Children with Autism Spectrum Disorder in Bangladesh : A Case-Control Study
- 2021
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Ingår i: Nature and Science of Sleep. - : Dove Medical Press. - 1179-1608. ; 13, s. 673-682
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sleep problems in children with Autism Spectrum Disorder (ASD) are highly prevalent, but little information is available on this issue in low- to middle-income countries (LMIC) such as Bangladesh. Therefore, the present study investigated the prevalence and socio-demographic determinants of ASD sleep disturbances in a comparison with typically developing children (TDC).Methods: A cross-sectional interview study was carried out within a total of 446 Bangladeshi mothers, whose children's mean age was 8.1 +/- 2.9 years (151 ASD [8.5 +/- 2.7 years] and 295 TDC [7.9 +/- 2.9 years]); in addition to socio-demographics, the Child Sleep Habit Questionnaire (CSHQ) was used, and a cut-off score of 41 out of 93 points considered as reflecting sleep problems.Results: About 89.7% of the children reported having problems in sleep, with ASD reporting higher frequency vs TDC (94.00% vs 87.50%; chi(2)=4.678, p=0.031). The overall mean CSHQ score was 48.7 +/- 7.6 in total sample, whereas ASD children reported higher scores compared to TDCs (50.9 +/- 8.1 vs 47.5 +/- 7.0, p< 0.001). Similarly, subscales of CSHQ such as sleep duration (4.23 +/- 1.56 vs 3.90 +/- 1.31, p=0.017), sleep anxiety (7.23 +/- 2.05 vs 6.45 +/- 1.92, p< 0.001), night waking (3.82 +/- 1.07 vs 3.17 +/- 1.89, p< 0.001), parasomnias (8.86 +/- 2.06 vs 7.85 +/- 2.27, p< 0.001), and sleep disordered breathing (4.02 +/- 2.92 vs 3.43 +/- 2.07, p=0.014) were more problematic among ASD compared to TDC. Lastly, 28.5% of ASD reported taking sleep-related medications vs 0.3% for TDC (n=1).Conclusion: Bangladeshi ASD children are highly likely to manifest sleep disturbances, which warrant urgent implementation of parental educational and support programs to mitigate the impact of sleep problems in ASD families.
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| 12. |
- Vijayakrishnan, Jayaram, et al.
(författare)
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A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:3, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10-9). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology.
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