Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese

Background: Genome-wide association studies (GWAS) in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs) that influence colorectal cancer (CRC) risk. Methods: We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs), in high linkage disequilibrium (LD, r2≥0.8) and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH) cases and controls. Results: Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR) ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88) but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20). Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58) but not women (OR = 1.07, 95% CI: 0.88-1.29), suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1). Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies. Conclusions: The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified. © 2012 Thean et al

Hyaluronic acid in viscous malignant mesothelioma pleural effusion

© 2020 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight

Views of healthcare professionals regarding barriers and facilitators for a Fracture Liaison Service in Malaysia.

This study aimed to explore the views of healthcare professionals regarding the barriers and facilitators for a Fracture Liaison Service (FLS) in Malaysia. The qualitative study was conducted from February to December 2021 at a tertiary hospital in Malaysia. Doctors, nurses, pharmacists, and policymakers were recruited via purposive sampling. Semi-structured in-depth interviews were conducted until thematic saturation was achieved. Data were transcribed verbatim and analysed using thematic analysis. Thirty participants [doctors (n = 13), nurses (n = 8), pharmacists (n = 8), and policymakers (n = 1)] with 2-28 years of working experience were recruited. Three themes emerged: 1) Current delivery of secondary fracture prevention; 2) Importance of secondary fracture prevention, and 3) FLS sustainability. Some participants reported that the current post-hip fracture care was adequate, whilst some expressed concerns about the lack of coordination and continuity of care, especially in non-hip fragility fracture care. Most participants recognised the importance of secondary fracture prevention as fracture begets fracture, highlighting the need for a FLS to address this care gap. However, some were concerned about competing priorities. To ensure the sustainability of a FLS, cost-effectiveness data, support from relevant stakeholders, increased FLS awareness among patients and healthcare professionals, and a FLS coordinator were required. Training and financial incentives may help address the issue of low confidence and encourage the nurses to take on the FLS coordinator role. Overall, all participants believed that there was a need for a FLS to improve the delivery of secondary fracture prevention. Addressing concerns such as lack of confidence among nurses and lack of awareness can help improve FLS sustainability

The Fear of Missing Out

This paper seeks to conceptualize the phenomenon known as the “Fear of Missing Out” by developing and validating a measurement scale – “Fear of Missing Out” (FOMOSCALE) to be used in a marketing context. It will also further explore various antecedents that may impact on FOMO. The study suggests an alternative approach towards the conceptualization of FOMO by defining it as a personality trait as opposed to an outcome of a behavior

Chromosome 19q13 disruption alters expressions of CYP2A7, MIA and MIA-RAB4B lncRNA and contributes to FAP-like phenotype in APC mutation-negative familial colorectal cancer patients.

Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APC-mutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender-matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions. Long-range polymerase chain reaction (PCR) confirmed chromosome 19q13 deletion, which was subsequently found in one other family. The 32 kb deleted region harbors the CYP2A7 gene and was enriched with enhancer, repressor and insulator sites. The wildtype allele was lost in the polyps of the proband. Further, real-time RT-PCR assays showed that expressions of MIA and MIA-RAB4B located 35 kb upstream of the deletion, were up-regulated in the polyps compared to the matched mucosa of the proband. MIA-RAB4B, the read-through long non-coding RNA (lncRNA), RAB4B, PIM2 and TAOK1 share common binding site of a microRNA, miR-24, in their 3'UTRs. PIM2 and TAOK1, two target oncogenes of miR-24, were co-ordinately up-regulated with MIA-RAB4B in the polyps, suggesting that MIA-RAB4B could function as competitive endogenous RNA to titrate miR-24 away from its other targets. The data suggest that the 19.13 deletion disrupted chromatin boundary, leading to altered expression of several genes and lncRNA, could contribute to colorectal cancer via novel genetic and epigenetic mechanisms

Neutrophil-to-lymphocyte ratio in malignant pleural fluid: Prognostic significance

Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p&lt;0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04–1.18] vs 4.9 [3.0–8.3], p&lt;0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p&lt;0.001). In univariate analysis, NLR (&gt;0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054–2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089–2.928]; p = 0.022). Patients with pleural fluid NLR &gt; 0.745 had a significantly shorter median survival of 130 (95% CI 0–282) days compared to 312 (95% CI 195–428) days for pleural NLR &lt; 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019–3.096]; p&lt;0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.</jats:p