FBXL4: safeguarding against mitochondrial depletion through suppression of mitophagy.

Mitophagy is a critical mitochondrial quality control process that selectively removes dysfunctional or excess mitochondria through the autophagy-lysosome system. The process is tightly controlled to ensure cellular and physiological homeostasis. Insufficient mitophagy can result in failure to remove damaged mitochondria and consequent cellular degeneration, but it is equally important to appropriately restrain mitophagy to prevent excessive mitochondrial depletion. Here, we discuss our recent discovery that the SKP1-CUL1-F-box (SCF)-FBXL4 (F-box and leucine-rich repeat protein 4) E3 ubiquitin ligase localizes to the mitochondrial outer membrane, where it constitutively mediates the ubiquitination and degradation of BNIP3L/NIX and BNIP3 mitophagy receptors to suppress mitophagy. The post-translational regulation of BNIP3L and BNIP3 is disrupted in mitochondrial DNA depletion syndrome 13 (MTDPS13), a multi-systemic disorder caused by mutations in the FBXL4 gene and characterized by elevated mitophagy and mitochondrial DNA/mtDNA depletion in patient fibroblasts. Our results demonstrate that mitophagy is not solely stimulated in response to specific conditions but is instead also actively suppressed through the continuous degradation of BNIP3L and BNIP3 mediated by the SCF-FBXL4 ubiquitin ligase. Thus, cellular conditions or signaling events that prevent the FBXL4-mediated turnover of BNIP3L and BNIP3 on specific mitochondria are expected to facilitate their selective removal.

Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay.

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA.

FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors.

To maintain both mitochondrial quality and quantity, cells selectively remove damaged or excessive mitochondria through mitophagy, which is a specialised form of autophagy. Mitophagy is induced in response to diverse conditions, including hypoxia, cellular differentiation and mitochondrial damage. However, the mechanisms that govern the removal of specific dysfunctional mitochondria under steady-state conditions to fine-tune mitochondrial content are not well understood. Here, we report that SCFFBXL4 , an SKP1/CUL1/F-box protein ubiquitin ligase complex, localises to the mitochondrial outer membrane in unstressed cells and mediates the constitutive ubiquitylation and degradation of the mitophagy receptors NIX and BNIP3 to suppress basal levels of mitophagy. We demonstrate that the pathogenic variants of FBXL4 that cause encephalopathic mtDNA depletion syndrome (MTDPS13) do not efficiently interact with the core SCF ubiquitin ligase machinery or mediate the degradation of NIX and BNIP3. Thus, we reveal a molecular mechanism whereby FBXL4 actively suppresses mitophagy by preventing NIX and BNIP3 accumulation. We propose that the dysregulation of NIX and BNIP3 turnover causes excessive basal mitophagy in FBXL4-associated mtDNA depletion syndrome.

The Role of Non-Coding RNAs in Chromosomal Instability in Cancer.

Chromosomal instability (CIN) is characterized by an increased frequency of changes in chromosome structure or number and is regarded as a hallmark of cancer. CIN plays a prevalent role in tumorigenesis and cancer progression by assisting the cancer cells' phenotypic adaptation to stress, which have been tightly linked to therapy resistance and metastasis. Both CIN-inducing and CIN-repressing agents are being clinically tested for the treatment of cancer to increase CIN levels to unsustainable levels leading to cell death or to decrease CIN levels to limit the development of drug resistance, respectively. Non-coding RNAs (ncRNAs) including microRNAs and long ncRNAs (lncRNAs) have been fundamentally implicated in CIN. The miR-22, miR-26a, miR-28, and miR-186 target important checkpoint proteins involved in mediating chromosomal stability and their expression modulation has been directly related to CIN occurrence. lncRNAs derived from telomeric, centrosomal, and enhancer regions play an important role in mediating genome stability, while specific lncRNA transcripts including genomic instability inducing RNA called Ginir, P53-responsive lncRNA termed as GUARDIN, colon cancer-associated transcript 2, PCAT2, and ncRNA activated by DNA damage called NORAD have been shown to act within CIN-associated pathways. In this review, we discuss how these ncRNAs either maintain or disrupt the stability of chromosomes and how these mechanisms could be exploited for novel therapeutic approaches targeting CIN in cancer patients. SIGNIFICANCE STATEMENT: Chromosomal instability increases tumor heterogeneity and thereby assists the phenotypic adaptation of cancer cells, causing therapy resistance and metastasis. Several microRNAs and long non-coding RNAs that have been causally linked to chromosomal instability could represent novel therapeutic targets. Understanding the role of non-coding RNAs in regulating different genes involved in driving chromosomal instability will give insights into how non-coding RNAs can be utilized toward modifying chemotherapeutic regimens in different cancers.

Green Fabrication of Heterostructured CoTiO3/TiO2 Nanocatalysts for Efficient Photocatalytic Degradation of Cinnamic Acid.

In this work, CoTiO3/TiO2 (CTO/Ti) heterostructures were prepared by a hydrothermal procedure in a neutral medium using perovskite CoTiO3 and tetraisopropyl titanate. Characteristics of the synthesized catalysts were analyzed by various techniques including X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, UV-vis diffuse reflectance spectroscopy, Brunauer-Emmett-Teller adsorption-desorption, energy-dispersive X-ray spectroscopy, field emission scanning electron microscopy, high-resolution transmission electron microscopy, and point of zero charges. The activity in the photodegradation of cinnamic acid (CA) under UV-A irradiation of the CTO/Ti heterostructure was investigated and compared with individual materials TiO2 (Ti-w) and CoTiO3 (CTO). The investigation showed that the heterostructured CoTiO3/TiO2 catalyst with optimal composition (5% CTO) exhibited much higher photocatalytic activity for degradation of cinnamic acid than individual CoTiO3 and TiO2. Under the optimal conditions (C cat = 0.75 g/L, Q air = 0.3 L/min, and pH = 3.8) the 90 min conversion of cinnamic acid reached 80.9% on 5CTO/Ti, much higher than those of CTO (4.6%) and Ti-w (75.2%). It was found that the enhancement in activity for the CA removal of the CTO/Ti heterostructure was due to the construction of a heterojunction structure between TiO2(Ti-w) and CoTiO3 that resulted in an increase in the specific surface area and porosity, reduction of the band gap energy, and higher efficient separation of charge carriers on the surface to prevent recombination. Alternatively, a comparison of the recyclability of 5CTO/Ti and Ti-w was made for CA degradation. The results showed a decrease in the CA conversion by 38% on 5CTO/Ti and 48% on Ti-w after six reaction cycles.

Emission factors for Vietnamese beef cattle manure sun-drying and the effects of drying on manure microbial community.

Livestock manure and its management are significant sources of greenhouse gas (GHG). In most Southeast Asian countries, the current GHG emissions are estimated by the Intergovernmental Panel on Climate Change (IPCC) Tier 1 approach using default emission factors. Sun-drying is the dominant manure treatment in Vietnam, and in this study, we measured GHG emissions during manure drying using a chamber-based approach. Results show the emission factors for CH4 and N2O were 0.295 ± 0.078 g kg-1 volatile solids (VS) and 0.132 ± 0.136 g N2O-N kg-1 Ninitial, respectively. We monitored the total bacterial/archaeal community using 16S rRNA gene amplicon sequencing and measured the abundance of functional genes required for methanogenesis (mcrA), nitrification (amoA) and denitrification (nirK, nirS and nosZ) processes. Methane emission occurred only at the beginning of the drying process (days 1 to 3). The results of amplicon sequencing indicated that the relative abundance of methanogens also decreased during this period. Although some nitrification activity was detected, there was no significant N2O emission. These findings well describe the manure management system in south Vietnam and the GHG emission from this manure category, paving the way for higher Tier estimations using country-specific values.

A pharmacist-driven Food and Drug Administration incident surveillance and response program for compounded drugs.

PURPOSE: To provide an overview of compounding under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act, and to describe the pharmacist's role within the US Food and Drug Administration's (FDA's) Compounding Incidents Program, whose efforts are aimed at protecting the public against poor-quality compounded drugs through surveillance, review and response to adverse events and complaints. SUMMARY: Compounded drugs may serve an important medical need for patients who cannot be treated with medications approved by FDA; however, compounded drugs are not approved by FDA and are not subject to premarket review for safety, efficacy, or manufacturing quality; thus, they may pose safety risks to patients. Prompt reporting of adverse events or complaints related to compounding is important in identifying these risks and implementing safeguards to protect the public. FDA's Compounding Incidents Program consists of a team of pharmacists dedicated to the surveillance and review of adverse events and complaints and follow-up actions related to safety risks associated with compounded drugs. Pharmacists are a vital component of FDA's Compounding Incidents Program, utilizing their clinical skill set and regulatory knowledge to review and act on safety issues that affect public health. CONCLUSION: As FDA continues to expand the Compounding Incidents Program and its efforts to protect the public against poor-quality compounded drugs, we encourage the continued submission of adverse event reports by healthcare professionals and consumers to FDA's MedWatch reporting system in addition to adverse event reporting compliance by outsourcing facilities.

Controlling Phase Composition, Properties and Activity of TiO2 Nano-Photocatalyst Synthesized by Hydrothermal Technique in the Degradation of Cinnamic Acid Solution.

In this work, titanium oxide catalysts were synthesized by the hydrothermal method from titanium isopropoxide (TTIP) as a precursor under acidic (Ti-A1 and Ti-A2), neutral (Ti-W) and alkaline (Ti-B) media. Characteristics of the catalysts were identified by various methods including X-ray diffraction, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller adsorption, UV-Vis diffuse reflectance spectroscopy, transmission electron microscopy, and Raman spectroscopy. The phase composition and PZC value of the obtained catalysts depended on the hydrothermal medium and the amount of TTIP: pure anatase and brookite phase formed at neutral and alkaline medium, respectively; whereas acidic medium favored the formation of anatase/rutile mixed phase and anatase phase decreased with the increasing amount of TTIP. The band gap energy of the synthesized catalysts was approximately 3.08-3.23 eV. Photocatalytic activity of synthesized catalysts was surveyed in the degradation of cinnamic acid (CA) solution at various pH in the region from 3.8 to 9.0 under UV irradiation. Photocatalytic oxidation was favorable in an acidic environment. At acidic pH values (3.8 and 5.0), the CA conversion was in the order of Ti-A2 ≥ Ti-A1 > Ti-P25 > Ti-W ≫ Ti-B, whereas it followed Ti-P25 > Ti-A1 > Ti-A2 ≈ Ti-W > Ti-B at pH 7.0 as well as pH 9.0.

Facile and Scalable Fabrication of Porous Polystyrene Fibers for Oil Removal by Centrifugal Spinning.

The demand for an efficient oil sorbent with high sorption capacity, low cost, scalable fabrication, and high selectivity for the cleanup of spreading oil on water is increasingly urgent due to the frequent occurrence of oil spill accidents in seawater all over the world. In this study, porous polystyrene (PS) fibers with high hydrophobicity and superoleophilicity were directly fabricated by a centrifugal spinning method (CS). The effect of solvents, tetrahydrofuran (THF), and dimethylformamide (DMF) on the morphology and porous structure of the polystyrene fibers was evaluated by using scanning electron microscopy and nitrogen adsorption-desorption experiments. The formation mechanism for the porous structure on the fibers was also evaluated. The oil sorption capacities of the PS fibers for silicon oil, pump oil, and vegetable oil were investigated. The highest oil sorption capacity was found in PS fibers fabricated from PS solution with a THF/DMF weight ratio of 1/3, which exhibited the highest specific surface area, pore volume, and porosity. The high productivity and highly porous structure of PS fibers indicate that CS is a promising method to fabricate porous fibers for the cleanup of oil spills.

Target screening analysis of 970 semi-volatile organic compounds adsorbed on atmospheric particulate matter in Hanoi, Vietnam.

Vietnam's rapid economic development has resulted in dramatic increases in construction and the number of transportation vehicles. There is now growing public concern regarding increasing air pollution, especially in big cities; however, little information is available on air quality, particularly regarding semi-volatile organic compounds (SVOCs) adsorbed on atmospheric particulate matter. Here, we determined the frequency and concentrations of 970 SVOCs in 48 air particle samples collected by means of high-volume air sampling in Hanoi, Vietnam, by using a target screening method and a gas chromatography-mass spectrometry database. A total of 118 compounds (12.2% of the target compounds) were detected at least once in the samples, and the number of chemicals detected in each sample ranged from 85 to 103 (median, 92). For samples collected near a heavily trafficked road, the concentrations of target compounds in the samples were higher in samples collected during the day than in those collected at night, whereas the opposite was true for samples collected in a highly populated residential area with industrial activities related to the production of fresh noodles. Sixteen PAHs were detected at high concentrations in nearly 100% of the samples. Eighteen pesticides were detected, with permethrin being detected the most frequently (>70% samples), which can be explained by the use of permethrin-based Permecide 50 EC for dengue fever control during the sampling period. Endocrine-disrupting chemicals (i.e., bisphenol A, 4-nitrophenol) and pharmaceuticals and personal care products (diethyltoluamide, caffeine) were detected in over 90% of the samples. Seven sterols, five phthalate compounds and five organophosphorus flame retardants were detected in the samples. This is the first comprehensive survey of SVOCs adsorbed on atmospheric particulate matter in Vietnam, and as such, this study provides important new information about the frequency and concentrations of atmospheric SVOC contamination. The variety of chemicals detected in this study implies an abundance of pollution sources; further investigations to determine these pollution sources and the risks posed by the detected SVOCs to human health are warranted.

SHVC Tile-Based 360-Degree Video Streaming for Mobile VR: PC Offloading Over mmWave.

360-degree video streaming for high-quality virtual reality (VR) is challenging for current wireless systems because of the huge bandwidth it requires. However, millimeter wave (mmWave) communications in the 60 GHz band has gained considerable interest from the industry and academia because it promises gigabit wireless connectivity in the huge unlicensed bandwidth (i.e., up to 7 GHz). This massive unlicensed bandwidth offers great potential for addressing the demand for 360-degree video streaming. This paper investigates the problem of 360-degree video streaming for mobile VR using the SHVC, the scalable of High-Efficiency Video Coding (HEVC) standard and PC offloading over 60 GHz networks. We present a conceptual architecture based on advanced tiled-SHVC and mmWave communications. This architecture comprises two main parts. (1) Tile-based SHVC for 360-degree video streaming and optimizing parallel decoding. (2) Personal Computer (PC) offloading mechanism for transmitting uncompressed video (viewport only). The experimental results show that our tiled extractor method reduces the bandwidth required for 360-degree video streaming by more than 47% and the tile partitioning mechanism was improved by up to 25% in terms of the decoding time. The PC offloading mechanism was also successful in offloading 360-degree decoded (or viewport only) video to mobile devices using mmWave communication and the proposed transmission schemes.

Antibiotic resistance in Vietnam: moving towards a One Health surveillance system.

BACKGROUND: The international community strongly advocates the implementation of multi-sectoral surveillance policies for an effective approach to antibiotic resistance, in line with the One Health concept. To comply with these international recommendations, the Vietnamese government has issued an inter-ministerial surveillance strategy for antibiotic resistance, including an integrated surveillance system. However, one may question the ability and willingness of surveillance stakeholders to implement the collaborations required. To assess the feasibility of operationalising this strategy within the national context, we explored the role of key stakeholders in the strategy, as well as their abilities to comply with it. METHODS: We conducted a qualitative approach based on an iterative stakeholder mapping and analysis, in three distinct steps: (1) a description of the structure of the national surveillance strategy (literature review, key informant interviews); (2) an analysis of the key stakeholders' positions regarding the strategy (semi-structured interviews); (3) the identification of factors influencing the operationalisation of the collaborative surveillance strategy (comparison of data collected at the first and second steps). RESULTS: The mapping of the surveillance system, as well as the characterisation of key stakeholders according to organisational and functional attributes, underlined that inter-sectoral surveillance initiatives do exist, but that the organisation of the national surveillance system remains highly silo-oriented. Based on stakeholder perspectives, we identified seven factors that may influence the implementation of the One Health strategy at national level: governance and operational frameworks, divergence of institutional cultures, level of knowledge, technical capacities, allocation of resources, conflicting commercial interests and influence of international partners. CONCLUSIONS: The study suggests that the operationalisation of the collaborative surveillance strategy requires the full adhesion of stakeholders and the provision of appropriate resources. Based on these findings, we have proposed a guidance framework together with recommendations to move towards a more suitable governance and operational model for One Health surveillance of antibiotic resistance in Vietnam. To lever and promote successful inter-sectoral collaboration, a participatory "learning by doing" process could be applied to guide, frame and mentor stakeholders through the identification of appropriate levels of collaboration, depending on the expected positive impacts on the value of surveillance.

Two polymorphisms, rs2046210 and rs3803662, are associated with breast cancer risk in a Vietnamese case-control cohort.

Breast cancer is the most common cancer in women worldwide. Breast tumorigenesis encompasses both extrinsic and intrinsic factors. Among intrinsic aspects, the appearance of DNA variation can cause genetic instability, which may lead to carcinogenesis. Genome-wide association studies have found several potential breast cancer-associated single nucleotide polymorphisms (SNPs) in many different populations. Among these, seven (rs2046210, rs1219648, rs3817198, rs3803662, rs889312, rs10941679 and rs13281615) have been shown to be significantly associated with breast cancer risk in various populations including those very similar to the Vietnamese. Here, therefore, we have investigated the relationship between these SNPs and breast cancer risk in a Vietnamese population case-control cohort. Real-time PCR high-resolution melt analysis was performed to genotype 300 breast cancer cases and 325 healthy controls, and the association between the seven SNPs and breast cancer risk was determined by analyzing the differences in allelic and genotypic frequencies between case and control groups using R software. While five of the seven showed no association with breast cancer, there was a relationship between the other two SNPs, rs2046210 and rs3803662, and the risk of developing this disease in Vietnamese women. The A allele is the risk allele for both rs2046210 (OR [95% CI] = 1.43 [1.14 - 1.78], P = 0.0015) and rs3803662 (OR [95% CI] = 1.45 [1.16 - 1.83], P = 0.001). We conclude that two polymorphisms, rs2046210 in ESR1 and rs3803662 in TNRC9, are associated with breast cancer risk in the Vietnamese population.

Re-evaluation of the species of hookworms infecting dogs in Central Vietnam.

BACKGROUND: Differentiation of canine hookworm species is crucial from both a veterinary and public health standpoint. In Vietnam, three hookworm species, namely Ancylostoma caninum, Ancylostoma braziliense and Uncinaria stenocephala are reported to infect dogs. In light of the emerging distribution of A. ceylanicum in Asia, this study aims to re-evaluate the status of Ancylostoma in dogs in Vietnam. METHODS: Faecal samples collected from 200 community dogs in Dak Lak province were subjected to faecal floatation for the detection of hookworm eggs. Hookworm-positive samples were subjected to a PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) assay targeting the internal transcribed spacer (ITS) region of rDNA for hookworm species identification. A subset of hookworm-positive samples was also subject to haplotype characterisation at the cytochrome oxidase-1 (COX-1) gene. Detailed morphological criteria were utilised in addition to molecular markers, to identify adult hookworms recovered from necropsied dogs. RESULTS: Of 200 canine faecal samples, 111 (55.5 %) were positive for hookworm eggs on faecal flotation. Of these, 94/111 (84.7 %) were successfully amplified and assigned species status by PCR-RFLP targeting the ITS region. In total, 54.3 % (51/94) dogs harboured single infections with A. ceylanicum, 33.0 % (31/94) with A. caninum, and 12.7 % (12/94) harboured mixed infections with both A. ceylanicum and A. caninum. Adult worms recovered from necropsied dogs matched morphological description provided for A. ceylanicum, Looss (1911) for which the mediolateral and posteriolateral rays are parallel. Characterisation of the COX-1 gene placed all Vietnamese canine isolates of A. ceylanicum within the 'zoonotic' haplotype. CONCLUSION: Based on this information, it is apparent that the hookworms present in dogs in Vietnam are those of A. ceylanicum and not A. braziliense. Owing to the endemic nature of this significant zoonosis in dogs, the study strongly advocates for specific identification of this hookworm in human hookworm surveys.

High-concentration boron doping of graphene nanoplatelets by simple thermal annealing and their supercapacitive properties.

For the utilization of graphene in various energy storage and conversion applications, it must be synthesized in bulk with reliable and controllable electrical properties. Although nitrogen-doped graphene shows a high doping efficiency, its electrical properties can be easily affected by oxygen and water impurities from the environment. We here report that boron-doped graphene nanoplatelets with desirable electrical properties can be prepared by the simultaneous reduction and boron-doping of graphene oxide (GO) at a high annealing temperature. B-doped graphene nanoplatelets prepared at 1000 °C show a maximum boron concentration of 6.04 ± 1.44 at %, which is the highest value among B-doped graphenes prepared using various methods. With well-mixed GO and g-B2O3 as the dopant, highly uniform doping is achieved for potentially gram-scale production. In addition, as a proof-of-concept, highly B-doped graphene nanoplatelets were used as an electrode of an electrochemical double-layer capacitor (EDLC) and showed an excellent specific capacitance value of 448 F/g in an aqueous electrolyte without additional conductive additives. We believe that B-doped graphene nanoplatelets can also be used in other applications such as electrocatalyst and nano-electronics because of their reliable and controllable electrical properties regardless of the outer environment.

Graphene oxide nanosheet wrapped white-emissive conjugated polymer nanoparticles.

We have demonstrated the preparation of white-emissive conjugated polymer nanoparticles wrapped with graphene oxide (GO) nanosheets. Highly stable, GO-wrapped, poly(9,9-di-n-octylfluorenyl-2,7-diyl) nanoparticles (GO-PFO NPs) with diameters in the range 30-150 nm were successfully obtained by utilizing the GO nanosheets as an interface stabilizer in an emulsification process. The synthesized GO-PFO NPs exhibited unique white-emitting photoluminescence with a characteristic green-emissive broad band above 500 nm, which was distinct from the photoluminescent behavior of PFO NPs without GO. This green emission was deduced to originate from the presence of the GO nanosheet shell surrounding the PFO NPs, rather than from luminescence of GO itself or formation of keto defects in the PFO chain. PL decay analysis showed that the GO-wrapped PFO NPs had a longer luminescence lifetime in comparison to PFO NPs without GO, and highly efficient energy transfer to lower energy state induced by the GO occurred.

Genetic polymorphisms in miRNAs targeting the estrogen receptor and their effect on breast cancer risk.

Breast cancer is the cancer that most commonly affects women worldwide. This type of cancer is genetically complex, but is strongly linked to steroid hormone signaling systems. Because microRNAs act as translational regulators of multiple genes, including the steroid nuclear receptors, single nucleotide polymorphisms (SNPs) in microRNA genes can have potentially wide-ranging influences on breast cancer development. Thus, this study was conducted to investigate the relationships between six SNPs (rs6977848, rs199981120, rs185641358, rs113054794, rs66461782, and rs12940701) located in four miRNA genes predicted to target the estrogen receptor (miR-148a, miR-221, miR-186, and miR-152) and breast cancer risk in Caucasian Australian women. By using high resolution melt analysis (HRM) and polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), 487 samples including 225 controls and 262 cases were genotyped. Analysis of their genotype and allele frequencies indicated that the differences between case and control populations were not significant for rs6977848, rs66461782, and rs12940701 because their p-values are 0.81, 0.93, and 0.1, respectively, which are all above the threshold value (p = 0.05). Our data thus suggests that these SNPs do not affect breast cancer risk in the tested population. In addition, rs199981120, rs185641358, and rs113054794 could not be found in this population, suggesting that these SNPs do not occur in Caucasian Australians.