Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry

Oral Diseases and Quality of Life between Obese and Normal Weight Adolescents: A Two-Year Observational Study

This study aimed to investigate the association between oral disease burden and oral health related quality of life (OHRQoL) among overweight/obese (OW/OB) and normal weight (NW) Malaysian adolescents. A total of 397 adolescents were involved in the two-year prospective observational cohort study. OHRQOL was measured through a self-administered questionnaire containing the short version of the Malaysian Oral Health Impact Profile (OHIP[M]). Body mass index (BMI) was used for anthropometric measurement. Whilst, decayed, missing, and filled teeth (DMFT) index, Significant Caries Index (SiC), simplified basic periodontal examination (S-BPE), and gingival bleeding index (GBI) were used for clinical assessment tools. Higher dental caries prevalence was observed in the NW group while higher SiC was reported in the OW/OB group. Regardless of the obesity status, the prevalence of gingivitis (BPE code 1 and 2) was high in this study. A reduction of GBI prevalence was observed in the two-year follow-up results with an increased prevalence of OHRQoL impact in the OW/OB group compared to the NW group (p > 0.05). The findings from this study suggested that obesity status did not have influence over the burden of oral diseases and OHRQoL. It offers insights referring to the changes in adolescents’ oral diseases burden and OHRQoL

Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer

Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers cancer stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial transition (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found to be potent promoters of MET that inhibit tumorigenicity in basal-like breast cancer. Cell state transitions are defined by reprogramming of lipid metabolism. Retinoids bind cognate nuclear receptors, which target lipid metabolism genes, thereby redirecting fatty acids for β-oxidation in the mesenchymal cell state towards lipid storage in the epithelial cell state. Disruptions of key metabolic enzymes mediating this flux inhibit MET. Conversely, perturbations to fatty acid oxidation (FAO) rechannel fatty acid flux and promote a more epithelial cell phenotype, blocking EMT-driven breast cancer metastasis in animal models. FAO impinges on the epigenetic control of EMT through acetyl-CoA-dependent regulation of histone acetylation on EMT genes, thus determining cell states.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)National Medical Research Council (NMRC)National Research Foundation (NRF)National University of Singapore (NUS), Temasek LaboratoriesPublished versionThis research is supported by the National Medical Research Council, Singapore (OFIRG17may061, OFIRG19nov-0106, OFYIRG18May-0025, and CTGIIT18may0012); National Research Foundation Singapore (NRF-NRFF2015-04, NRFCRP22-2019-0003, NRF-CRP23-2019-0004, and NRFSBP-P4); National Cancer Institute Singapore Yong Siew Yoon Research Grant; Agency for Science, Technology and Research, Singapore (IAF-ICP I1901E0040); National University of Singapore via the Life Sciences Institute (LSI); and the Singapore Ministry of Education under its Research Centers of Excellence initiative

Imported monkeypox, Singapore

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.Published versio

Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results

10.3390/cancers14112714CANCERS141