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A review on phytoremediation of contaminants in air, water and soil

Wei Z, Van Le Q, Peng W, Yang Y, Yang H, Gu H, et al.

J Hazard Mater, 2021 02 05;403:123658.
PMID: 33264867 DOI: 10.1016/j.jhazmat.2020.123658

There is a global need to use plants to restore the ecological environment. There is no systematic review of phytoremediation mechanisms and the parameters for environmental pollution. Here, we review this situation and describe the purification rate of different plants for different pollutants, as well as methods to improve the purification rate of plants. This is needed to promote the use of plants to restore the ecosystems and the environment. We found that plants mainly use their own metabolism including the interaction with microorganisms to repair their ecological environment. In the process of remediation, the purification factors of plants are affected by many conditions such as light intensity, stomatal conductance, temperature and microbial species. In addition the efficiency of phytoremediation is depending on the plants species-specific metabolism including air absorption and photosynthesis, diversity of soil microorganisms and heavy metal uptake. Although the use of nanomaterials and compost promote the restoration of plants to the environment, a high dose may have negative impacts on the plants. In order to improve the practicability of the phytoremediation on environmental restoration, further research is needed to study the effects of different kinds of catalysts on the efficiency of phytoremediation. Thus, the present review provides a recent update for development and applications of phytoremediation in different environments including air, water, and soil.
A review on valorization of oyster mushroom and waste generated in the mushroom cultivation industry

Wan Mahari WA, Peng W, Nam WL, Yang H, Lee XY, Lee YK, et al.

J Hazard Mater, 2020 12 05;400:123156.
PMID: 32574879 DOI: 10.1016/j.jhazmat.2020.123156

A review of valorization of oyster mushroom species and waste generated in the mushroom cultivation is presented, with a focus on the cultivation and valorization techniques, conditions, current research status and particularly the hazard mitigation and value-added recovery of the waste mushroom substrate (WMS) - an abundant waste in mushroom cultivation industry. Based on the studies reviewed, the production rate of the present mushroom industry is inadequate to meet market demands. There is a need for the development of new mushroom cultivation methods that can guarantee an increase in mushroom productivity and quality (nutritional and medicinal properties). This review shows that the cylindrical baglog cultivation method is more advantageous compared with the wood tray cultivation method to improve the mushroom yield and cost efficiency. Approximately 5 kg of potentially hazardous WMS (spreading diseases in mushroom farm) is generated for production of 1 kg of mushroom. This encourages various valorization of WMS for use in agricultural and energy conversion applications, mainly as biocompost, plant growing media, and bioenergy. The use of WMS as biofertilizer has shown desirable performance compared to conventional chemical fertilizer, whilst the use of WMS as energy feedstock could produce cleaner bioenergy sources compared to conventional fuels.
A comparison of neurotoxicity in cerebellum produced by dermal application of chlorpyrifos in young and adult mice

Krishnan K, Mitra NK, Yee LS, Yang HM

J Neural Transm (Vienna), 2012 Mar;119(3):345-52.
PMID: 21922192 DOI: 10.1007/s00702-011-0715-5

Chlorpyrifos (CPF), an organophosphate pesticide inhibits acetylcholinesterase (AChE) and causes neuromuscular incoordination among children and elderly. The objectives of the present study were to compare the neurotoxic effects of dermal application of CPF on the cerebellum in the parameters of glial fibrillary acidic protein (GFAP) expression in young and adult mice and to correlate with the changes in acetylcholinesterase levels. Male Balb/c mice, 150 days old (adult) and 18 days old (young) were dermally applied with ½ LD(50) of CPF over the tails for 14 days. Serum AChE concentration was estimated and GFAP immunostaining was performed on sagittal paraffin sections through the vermis of cerebellum. Although reduced in both age-groups exposed to CPF, percentage of reduction in serum AChE was more in adult compared to the young. Under GFAP immunostaining, brown colour fibres and glial cells were observed in cerebellar cortex and medulla in both the experimental groups. The mean GFAP-positive glial cell count in cerebellar medulla per mm(2) of section was significantly (p
Fulltext Infrapatellar fat pad resection or preservation during total knee arthroplasty: a meta-analysis of randomized controlled trials

Sun C, Zhang X, Lee WG, Tu Y, Li H, Cai X, et al.

J Orthop Surg Res, 2020 Aug 05;15(1):297.
PMID: 32758250 DOI: 10.1186/s13018-020-01823-2

BACKGROUND: The infrapatellar fat pad (IPFP) or Hoffa's fat pad is often resected during total knee arthroplasty in order to improve visibility. However, the management of the IPFP during total knee arthroplasty (TKA) is the subject of an ongoing debate that has no clear consensus. The purpose of this review was to appraise if resection of the IPFP affects clinical outcomes.
METHODS: We conducted a meta-analysis to identify relevant randomized controlled trials involving infrapatellar fat pad resection and infrapatellar fat pad preservation during total knee arthroplasty in electronic databases, including Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database, up to March 2020.
RESULTS: Nine randomized controlled trials, involving 783 TKAs (722 patients), were included in the systematic review. Outcome measures included patellar tendon length (PTL), Insall-Salvati ratio (ISR), rate of anterior knee pain, Knee Society Scores (KSS), and knee range of motion. The meta-analysis identified a trend toward the shortening of the patellar tendon with IPFP resection at 6 months (P = 0.0001) and 1 year (P = 0.001). We found no statistical difference in ISR (P = 0.87), rate of anterior knee pain within 6 months (p = 0.45) and 1 year (p = 0.38), KSS at 1 year (p = 0.77), and knee range of motion within 6 months (p = 0.61) and 1 year (0.46).
CONCLUSION: Based on the available level I evidence, we were unable to conclude that one surgical technique of IPFP can definitively be considered superior over the other. More adequately powered and better-designed randomized controlled trial (RCT) studies with long-term follow-up are required to produce evidence-based guidelines regarding IPFP resection.
Morphological and genetical changes of endothelial progenitor cells after in-vitro conversion into photoreceptors

Qiang S, Alsaeedi HA, Yuhong C, Yang H, Tong L, Kumar S, et al.

J. Photochem. Photobiol. B, Biol., 2018 Jun;183:127-132.
PMID: 29704860 DOI: 10.1016/j.jphotobiol.2018.04.003

BACKGROUND: Retinal degeneration is a condition ensued by various ocular disorders such as artery occlusion, diabetic retinopathy, retrolental fibroplasia and retinitis pigmentosa which cause abnormal loss of photoreceptor cells and lead to eventual vision impairment. No efficient treatment has yet been found, however, the use of stem cell therapy such as bone marrow and embryonic stem cells has opened a new treatment modality for retinal degenerative diseases. The major goal of this study is to analyze the potential of endothelial progenitor cells derived from bone marrow to differentiate into retinal neural cells for regenerative medicine purposes.
METHODS: In this study, endothelial progenitor cells were induced in-vitro with photoreceptor growth factor (taurine) for 21 days. Subsequently, the morphology and gene expression of CRX and RHO of the photoreceptors-induced EPCs were examined through immunostaining assay.
FINDINGS: The results indicated that the induced endothelial progenitor cells demonstrated positive gene expression of CRX and RHO. Our findings suggested that EPC cells may have a high advantage in cell replacement therapy for treating eye disease, in addition to other neural diseases, and may be a suitable cell source in regenerative medicine for eye disorders.
Fulltext Effects of Inflammatory Disease on Clinical Progression and Treatment of Ischiogluteal Bursitis: A Retrospective Observational Study

Roh YH, Yoo SJ, Choi YH, Yang HC, Nam KW

Malays Orthop J, 2020 Nov;14(3):32-41.
PMID: 33403060 DOI: 10.5704/MOJ.2011.007

Introduction: The symptoms of Ischiogluteal Bursitis (IGB) are often nonspecific and atypical, and its diagnosis is more challenging. Moreover, it is difficult to predict cases of chronic progression or poor treatment response. Therefore, the aim of this study was to investigate the clinical course of IGB patients and identify factors that are predictive of failure of conservative treatment.
Materials and Methods: Our study consisted of IGB patients diagnosed between 2010 March and 2016 December who had been followed-up for at least one year. Structured questionnaires and medical records were reviewed to analyse demographic characteristics, lifestyle patterns, blood tests, and imaging studies. We categorized the cases into two groups based on the response to conservative treatment and the need for surgical intervention.
Results: The most common initial chief symptoms were buttock pains in 24 patients (37.5%). Physical examinations showed the tenderness of ischial tuberosity area in 59 (92.2%) patients, but no specific findings were confirmed in 5 patients (7.8%). 51 patients (79.7%) responded well to the conservative management, 11 patients (17.2%) needed injection, and 2 patients (3.1%) had surgical treatment performed due to continuous recurrence. There was no difference in demographic and blood lab data between the two groups. However, the incidence of inflammatory diseases (response group: 10.3% vs non-response group: 66.7%, p=0.004) was significantly different between the two groups.
Conclusion: The diagnosis of IGB can be missed due to variations in clinical symptoms, and cautions should be exercised in patients with inflammatory diseases as conservative treatment is less effective in them, leading to chronic progression of IGB.
Adsorption of Pyrethroids in Water by Calcined Shell Powder: Preparation, Characterization, and Mechanistic Analysis

Ma X, Tao S, Fu S, Yang H, Lin B, Lou Y, et al.

Materials (Basel), 2023 Mar 31;16(7).
PMID: 37049096 DOI: 10.3390/ma16072802

Pyrethroids are common contaminants in water bodies. In this study, an efficient mussel shell-based adsorbent was prepared, the effects of factors (calcination temperature, calcination time, and sieved particle size) on the pyrethroid adsorption capacity from calcined shell powder were investigated via Box-Behnken design, and the prediction results of the model were verified. By characterizing (scanning electron microscopy, X-ray diffraction, Fourier infrared spectroscopy, and Brunauer-Emmett-Teller measurements) the adsorbent before and after the optimized preparation process, the results showed that calcined shell powder had a loose and porous structure, and the main component of the shell powder under optimized condition was calcium oxide. The adsorption mechanism was also investigated, and the analysis of adsorption data showed that the Langmuir, pseudo second-order, and intra-particle diffusion models were more suitable for describing the adsorption process. The adsorbent had good adsorption potential for pyrethroids, the adsorption capacity of the two pesticides was 1.05 and 1.79 mg/g, and the removal efficiency was over 40 and 70% at the maximum initial concentration, respectively.
Fulltext Radiation-Grafted Anion-Exchange Membrane for Fuel Cell and Electrolyzer Applications: A Mini Review

Lim KL, Wong CY, Wong WY, Loh KS, Selambakkannu S, Othman NAF, et al.

Membranes (Basel), 2021 May 27;11(6).
PMID: 34072048 DOI: 10.3390/membranes11060397

This review discusses the roles of anion exchange membrane (AEM) as a solid-state electrolyte in fuel cell and electrolyzer applications. It highlights the advancement of existing fabrication methods and emphasizes the importance of radiation grafting methods in improving the properties of AEM. The development of AEM has been focused on the improvement of its physicochemical properties, including ionic conductivity, ion exchange capacity, water uptake, swelling ratio, etc., and its thermo-mechano-chemical stability in high-pH and high-temperature conditions. Generally, the AEM radiation grafting processes are considered green synthesis because they are usually performed at room temperature and practically eliminated the use of catalysts and toxic solvents, yet the final products are homogeneous and high quality. The radiation grafting technique is capable of modifying the hydrophilic and hydrophobic domains to control the ionic properties of membrane as well as its water uptake and swelling ratio without scarifying its mechanical properties. Researchers also showed that the chemical stability of AEMs can be improved by grafting spacers onto base polymers. The effects of irradiation dose and dose rate on the performance of AEM were discussed. The long-term stability of membrane in alkaline solutions remains the main challenge to commercial use.
Fulltext All-Optical Modulation Technology Based on 2D Layered Materials

Yang H, Wang Y, Tiu ZC, Tan SJ, Yuan L, Zhang H

Micromachines (Basel), 2022 Jan 07;13(1).
PMID: 35056256 DOI: 10.3390/mi13010092

In the advancement of photonics technologies, all-optical systems are highly demanded in ultrafast photonics, signal processing, optical sensing and optical communication systems. All-optical devices are the core elements to realize the next generation of photonics integration system and optical interconnection. Thus, the exploration of new optoelectronics materials that exhibit different optical properties is a highlighted research direction. The emerging two-dimensional (2D) materials such as graphene, black phosphorus (BP), transition metal dichalcogenides (TMDs) and MXene have proved great potential in the evolution of photonics technologies. The optical properties of 2D materials comprising the energy bandgap, third-order nonlinearity, nonlinear absorption and thermo-optics coefficient can be tailored for different optical applications. Over the past decade, the explorations of 2D materials in photonics applications have extended to all-optical modulators, all-optical switches, an all-optical wavelength converter, covering the visible, near-infrared and Terahertz wavelength range. Herein, we review different types of 2D materials, their fabrication processes and optical properties. In addition, we also summarize the recent advances of all-optical modulation based on 2D materials. Finally, we conclude on the perspectives on and challenges of the future development of the 2D material-based all-optical devices.
Fulltext A Positively Selected MAGEE2 LoF Allele Is Associated with Sexual Dimorphism in Human Brain Size and Shows Similar Phenotypes in Magee2 Null Mice

Szpak M, Collins SC, Li Y, Liu X, Ayub Q, Fischer MC, et al.

Mol Biol Evol, 2021 Dec 09;38(12):5655-5663.
PMID: 34464968 DOI: 10.1093/molbev/msab243

A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation, and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10-6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of gray matter in males (P = 0.00094), and smaller volumes of gray (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behavior or cognition, but it might have been the driving force underlying the positive selection in humans.
Fulltext Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations

Arciero E, Kraaijenbrink T, Asan, Haber M, Mezzavilla M, Ayub Q, et al.

Mol Biol Evol, 2018 Aug 01;35(8):1916-1933.
PMID: 29796643 DOI: 10.1093/molbev/msy094

We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India, or Tibet at over 500,000 SNPs, and analyzed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resembled other South and East Asians, but in addition displayed their own specific ancestral component and showed strong population structure and genetic drift. We also found evidence for multiple admixture events involving Himalayan populations and South/East Asians between 200 and 2,000 years ago. In comparisons with available ancient genomes, the Himalayans, like other East and South Asian populations, showed similar genetic affinity to Eurasian hunter-gatherers (a 24,000-year-old Upper Palaeolithic Siberian), and the related Bronze Age Yamnaya. The high-altitude Himalayan populations all shared a specific ancestral component, suggesting that genetic adaptation to life at high altitude originated only once in this region and subsequently spread. Combining four approaches to identifying specific positively selected loci, we confirmed that the strongest signals of high-altitude adaptation were located near the Endothelial PAS domain-containing protein 1 and Egl-9 Family Hypoxia Inducible Factor 1 loci, and discovered eight additional robust signals of high-altitude adaptation, five of which have strong biological functional links to such adaptation. In conclusion, the demographic history of Himalayan populations is complex, with strong local differentiation, reflecting both genetic and cultural factors; these populations also display evidence of multiple genetic adaptations to high-altitude environments.
Fulltext Synthesis of 2,4-Diaminopyrimidine Core-Based Derivatives and Biological Evaluation of Their Anti-Tubercular Activities

Ouyang Y, Yang H, Zhang P, Wang Y, Kaur S, Zhu X, et al.

Molecules, 2017 Sep 22;22(10).
PMID: 28937657 DOI: 10.3390/molecules22101592

Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 μg/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays.
Fulltext Author Correction: Dense sampling of bird diversity increases power of comparative genomics

Feng S, Stiller J, Deng Y, Armstrong J, Fang Q, Reeve AH, et al.

Nature, 2021 Apr;592(7856):E24.
PMID: 33833441 DOI: 10.1038/s41586-021-03473-8
Fulltext Dense sampling of bird diversity increases power of comparative genomics

Feng S, Stiller J, Deng Y, Armstrong J, Fang Q, Reeve AH, et al.

Nature, 2020 11;587(7833):252-257.
PMID: 33177665 DOI: 10.1038/s41586-020-2873-9

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.
Fulltext A ring-like accretion structure in M87 connecting its black hole and jet

Lu RS, Asada K, Krichbaum TP, Park J, Tazaki F, Pu HY, et al.

Nature, 2023 Apr;616(7958):686-690.
PMID: 37100940 DOI: 10.1038/s41586-023-05843-w

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
Fulltext Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3

Wang HY, Yang H, Holm M, Tom H, Oltion K, Al-Khdhairawi AAQ, et al.

Nat Chem, 2022 Dec;14(12):1443-1450.
PMID: 36123449 DOI: 10.1038/s41557-022-01039-3

Ternatin-family cyclic peptides inhibit protein synthesis by targeting the eukaryotic elongation factor-1α. A potentially related cytotoxic natural product ('A3') was isolated from Aspergillus, but only 4 of its 11 stereocentres could be assigned. Here, we synthesized SR-A3 and SS-A3-two out of 128 possible A3 epimers-and discovered that synthetic SR-A3 is indistinguishable from naturally derived A3. Relative to SS-A3, SR-A3 exhibits an enhanced residence time and rebinding kinetics, as revealed by single-molecule fluorescence imaging of elongation reactions catalysed by eukaryotic elongation factor-1α in vitro. An increased residence time-stereospecifically conferred by the unique β-hydroxyl in SR-A3-was also observed in cells. Consistent with its prolonged duration of action, thrice-weekly dosing with SR-A3 led to a reduced tumour burden and increased survival in an aggressive Myc-driven mouse lymphoma model. Our results demonstrate the potential of SR-A3 as a cancer therapeutic and exemplify an evolutionary mechanism for enhancing cyclic peptide binding kinetics via stereospecific side-chain hydroxylation.
Fulltext Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Lawrenson K, Li Q, Kar S, Seo JH, Tyrer J, Spindler TJ, et al.

Nat Commun, 2015 Sep 22;6:8234.
PMID: 26391404 DOI: 10.1038/ncomms9234

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
Fulltext Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, et al.

Nat Genet, 2015 Feb;47(2):164-71.
PMID: 25581431 DOI: 10.1038/ng.3185

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
Fulltext Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Phelan CM, Kuchenbaecker KB, Tyrer JP, Kar SP, Lawrenson K, Winham SJ, et al.

Nat Genet, 2017 May;49(5):680-691.
PMID: 28346442 DOI: 10.1038/ng.3826

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Fulltext Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Hampras SS, Sucheston-Campbell LE, Cannioto R, Chang-Claude J, Modugno F, Dörk T, et al.

Oncotarget, 2016 10 25;7(43):69097-69110.
PMID: 27533245 DOI: 10.18632/oncotarget.10215

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.
METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.
RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).
CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

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