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12 results on '"Hanis Nazihah Hasmad"'

1. Electrospun Fiber-Coated Human Amniotic Membrane: A Potential Angioinductive Scaffold for Ischemic Tissue Repair

Author

Hanis Nazihah Hasmad, Ruszymah Bt Hj Idrus, Nadiah Sulaiman, and Yogeswaran Lokanathan

Subjects
Vascular Endothelial Growth Factor A, electrospun fiber, QH301-705.5, Cell Survival, Neovascularization, Physiologic, Biocompatible Materials, angiogenesis, human amniotic membrane, skeletal myoblast, ischemia, Catalysis, Inorganic Chemistry, Polylactic Acid-Polyglycolic Acid Copolymer, Cell Movement, Ischemia, Angiopoietin-1, Human Umbilical Vein Endothelial Cells, Humans, Regeneration, Amnion, Biology (General), Physical and Theoretical Chemistry, Muscle, Skeletal, QD1-999, Molecular Biology, Spectroscopy, Muscle Cells, Tissue Engineering, Tissue Scaffolds, Interleukin-8, Organic Chemistry, virus diseases, food and beverages, General Medicine, Fibroblasts, Computer Science Applications, Chemistry, Culture Media, Conditioned
Abstract

Cardiac patch implantation helps maximize the paracrine function of grafted cells and serves as a reservoir of soluble proangiogenic factors required for the neovascularization of infarcted hearts. We have previously fabricated a cardiac patch, EF-HAM, composed of a human amniotic membrane (HAM) coated with aligned PLGA electrospun fibers (EF). In this study, we aimed to evaluate the biocompatibility and angiogenic effects of EF-HAM scaffolds with varying fiber thicknesses on the paracrine behavior of skeletal muscle cells (SkM). Conditioned media (CM) obtained from SkM-seeded HAM and EF-HAM scaffolds were subjected to multiplex analysis of angiogenic factors and tested on HUVECs for endothelial cell viability, migration, and tube formation analyses. All three different groups of EF-HAM scaffolds demonstrated excellent biocompatibility with SkM. CM derived from SkM-seeded EF-HAM 7 min scaffolds contained significantly elevated levels of proangiogenic factors, including angiopoietin-1, IL-8, and VEGF-C compared to plain CM, which was obtained from SkM cultured on the plain surface. CM obtained from all SkM-seeded EF-HAM scaffolds significantly increased the viability of HUVECs compared to plain CM after five days of culture. However, only EF-HAM 7 min CM induced a higher migration capacity in HUVECs and formed a longer and more elaborate capillary-like network on Matrigel compared with plain CM. Surface roughness and wettability of EF-HAM 7 min scaffolds might have influenced the proportion of skeletal myoblasts and fibroblasts growing on the scaffolds and subsequently potentiated the angiogenic paracrine function of SkM. This study demonstrated the angioinductive properties of EF-HAM composite scaffold and its potential applications in the repair and regeneration of ischemic tissues.

Published
2022

2. Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author

Natalia Bogdanova, Karen Carty, Brooke L. Fridley, Argyrios Ziogas, Matthias Dürst, Ignace Vergote, Anxhela Gjyshi, Barry P. Rosen, Heli Nevanlinna, Anna H. Wu, Estrid Høgdall, Sandra Orsulic, Alice W. Lee, Liisa M. Pelttari, Timothy P. Hughes, Francesmary Modugno, Kirsten B. Moysich, Malcolm C. Pike, Xifeng Wu, Anja Rudolph, Philipp Harter, Jolanta Lissowska, Edwin S. Iversen, Susan J. Ramus, Douglas F. Easton, Julie M. Cunningham, Katja K.H. Aben, Liv Cecilie Vestrheim Thomsen, Lynne R. Wilkens, Lene Lundvall, Melissa Buckley, Shelley S. Tworoger, Simon A. Gayther, Allan Jensen, Robert P. Edwards, Angela Brooks-Wilson, Jonathan Tyrer, Rosalind Glasspool, Soo Hwang Teo, Gerhard A. Coetzee, Renato S. Carvalho, Matthew L. Freedman, Jan Lubinski, Diether Lambrechts, Ellen L. Goode, Wei Zheng, Thomas A. Sellers, Y. Ann Chen, Harvey A. Risch, Leon F.A.G. Massuger, Kathryn L. Terry, Beata Spiewankiewicz, Andrew Berchuck, Jennifer A. Doherty, Usha Menon, Christine Walsh, Louise A. Brinton, Hoda Anton-Culver, Alice S. Whittemore, Kunle Odunsi, Linda S. Cook, John R. McLaughlin, Ralf Bützow, Joseph L. Kelley, Fiona Bruinsma, Iwona K. Rzepecka, Jennifer B. Permuth, Dong Liang, Jolanta Kupryjanczyk, Nicolas Wentzensen, Karen H. Lu, Marc T. Goodman, Katharina Bischof, Yin Ling Woo, Nicholas T. Woods, Yurii B. Shvetsov, Yu-Tang Gao, Ya Yu Tsai, Andreas du Bois, Aleksandra Gentry-Maharaj, Weiva Sieh, Nadeem Siddiqui, Mary Anne Rossing, Joellen M. Schildkraut, Thilo Dörk, Douglas A. Levine, RL Milne, Lotte Ansgaard Thomsen, Sara H. Olson, Jenny Chang-Claude, Jacek Gronwald, Hannah P. Yang, Peter Hillemanns, Hamed S. Najafabadi, Ed Dicks, Alvaro N.A. Monteiro, Tanja Pejovic, Diana Eccles, Peter A. Fasching, Honglin Song, Hanis Nazihah Hasmad, Beth Y. Karlan, Matthias W. Beckmann, Pamela J. Thompson, Dennis J. Hazelett, Elizabeth M. Poole, Sandrina Lambrechts, Alexander Hein, Gustavo Mendoza-Fandiño, Arif B. Ekici, Kate Lawrenson, Xiao-Ou Shu, Linda E. Kelemen, Elisa V. Bandera, Michelle A.T. Hildebrandt, Clareann H. Bunker, Madalene Earp, Anne M. van Altena, Simon G. Coetzee, Ally Yang, Roberta B. Ness, James Paul, Cezary Cybulski, Valerie McGuire, Line Bjørge, Lara E. Sucheston-Campbell, Ian G. Campbell, Ian McNeish, Shan Wang-Gohrke, Daniel W. Cramer, Paulo C Lyra, Yukie Bean, Agnieszka Dansonka-Mieszkowska, Melissa C. Southey, Celeste Leigh Pearce, Howard C. Shen, Susanne K. Kjaer, Keitaro Matsuo, Anna Jakubowska, Paul D.P. Pharoah, Lambertus A. Kiemeney, Graham G. Giles, Irene Orlow, Sean J. Yoder, Reidun K. Kopperud, Jenny Lester, Georgia Chenevix-Trench, Houtan Noushmehr, and Catherine M. Phelan

Subjects
0301 basic medicine, Cancer Research, Linkage disequilibrium, Cell Cycle Proteins, Genome-wide association study, Single-nucleotide polymorphism, Locus (genetics), Carcinoma, Ovarian Epithelial, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Genetic Predisposition to Disease, Scaffold/matrix attachment region, Gene, Genotyping, Ovarian Neoplasms, Genetics, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Base Sequence, Chromosome Mapping, DNA, Neoplasm, medicine.disease, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Cystadenocarcinoma, Serous, 3. Good health, DNA-Binding Proteins, HEK293 Cells, 030104 developmental biology, Oncology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Female, MAPEAMENTO GENÉTICO, Chromosomes, Human, Pair 9, Ovarian cancer, Genome-Wide Association Study
Abstract

Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. Significance: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene. See related commentary by Choi and Brown, p. 439

Published
2019

3. Decellularization and genipin crosslinking of amniotic membrane suitable for tissue engineering applications

Author

Siti Fatmah Azizi, Siti Solehah Zainol, Yogeswaran Lokanathan, Nabil Mohamad Iman, Hanis Nazihah Hasmad, Mohd Reusmaazran Yusof, Rajasegaran Muniandy, Haslinda Abd Aziz, Salina Husain, and Sarumathi Gobinathan

Subjects
0301 basic medicine, animal structures, Biocompatibility, Biomedical Engineering, Biophysics, Bioengineering, Biocompatible Materials, 02 engineering and technology, Turbinates, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Tissue engineering, Thermolysin, Pregnancy, medicine, Humans, Iridoids, Amnion, Collagenases, Cells, Cultured, Extracellular Matrix Proteins, Decellularization, Chromatography, Tissue Engineering, Tissue Scaffolds, food and beverages, Fibroblasts, 021001 nanoscience & nanotechnology, 030104 developmental biology, Membrane, Cross-Linking Reagents, chemistry, Genipin, Collagenase, Female, Collagen, Swelling, medicine.symptom, 0210 nano-technology, medicine.drug
Abstract

Amniotic membrane has the potential to be used as scaffold in various tissue engineering applications. However, increasing its biostability at the same time maintaining its biocompatibility is important to enhance its usage as a scaffold. This studied characteristics genipin-crosslinked amniotic membrane as a bioscaffold. Redundant human amniotic membranes (HAM) divided into native (nAM), decellularized (dAM) and genipin-crosslinked (clAM) groups. The dAM and clAM group were decellularized using thermolysin (TL) and sodium hydroxide (NaOH) solution. Next, clAM group was crosslinked with 0.5% and 1.0% (w/v) genipin. The HAM was then studied for in vitro degradation, percentage of swelling, optical clarity, ultrastructure and mechanical strength. Meanwhile, fibroblasts isolated from nasal turbinates were then seeded onto nAM, dAM and clAM for biocompatibility studies. clAM had the slowest degradation rate and were still morphologically intact after 30 days of incubation in 0.01% collagenase type 1 solution. The dAM had a significantly highest percentage of swelling than other groups (p 0.05). Besides, the dAM retained the collagen content at similar level of nAM. Although the dAM had highest mechanical strength compared to the rest of the groups, the differences were statistically insignificant. Cell attachment on dAM and 0.5% clAM was higher compared to that on nAM and 1.0% clAM. In conclusion, clAM have better biostability and biocompatibility compared to the nAM and dAM. Together with other suitable characteristics of the clAM such as percentage of swelling, structural integrity and ECM content, clAM is suitable as scaffold for various tissue engineering applications.

Published
2018

4. Human Amniotic Membrane with Aligned Electrospun Fiber as Scaffold for Aligned Tissue Regeneration

Author

Ruszymah Bt Hj Idrus, Shiplu Roy Chowdhury, Zainul Rashid Mohd Razi, Mohd Reusmaazran Yusof, and Hanis Nazihah Hasmad

Subjects
0301 basic medicine, Scaffold, Materials science, Polymers, Biomedical Engineering, Nanofibers, Medicine (miscellaneous), Bioengineering, Biocompatible Materials, 02 engineering and technology, 03 medical and health sciences, chemistry.chemical_compound, Tissue engineering, immune system diseases, hemic and lymphatic diseases, Materials Testing, Humans, Amnion, Muscle, Skeletal, Cells, Cultured, Cell Proliferation, Decellularization, Tissue Engineering, Tissue Scaffolds, technology, industry, and agriculture, virus diseases, food and beverages, Biomaterial, 021001 nanoscience & nanotechnology, Electrospinning, Extracellular Matrix, PLGA, 030104 developmental biology, chemistry, Nanofiber, Tissue Decellularization, Female, 0210 nano-technology, Biomedical engineering
Abstract

Fabrication of composite scaffolds is one of the strategies proposed to enhance the functionality of tissue-engineered scaffolds for improved tissue regeneration. By combining multiple elements together, unique biomimetic scaffolds with desirable physical and mechanical properties can be tailored for tissue-specific applications. Despite having a highly porous structure, the utility of electrospun fibers (EF) as scaffold is usually hampered by their insufficient mechanical strength. In this study, we attempted to produce a mechanically competent scaffold with cell-guiding ability by fabricating aligned poly lactic-co-glycolic acid (PLGA) fibers on decellularized human amniotic membrane (HAM), known to possess favorable tensile and wound healing properties. Decellularization of HAM in 18.75 μg/mL of thermolysin followed by a brief treatment in 0.25 M sodium hydroxide efficiently removed the amniotic epithelium and preserved the ultrastructure of the underlying extracellular matrix. The electrospinning of 20% (w/v) PLGA 50:50 polymer on HAM yielded beadless fibers with straight morphology. Subsequent physical characterization revealed that EF-HAM scaffold with a 3-min fabrication had the most aligned fibers with the lowest fiber diameter in comparison with EF-HAM 5- and 7-min scaffolds. Hydrated EF-HAM scaffolds with 3-min deposition had a greater tensile strength than the other scaffolds despite having thinner fibers. Nevertheless, wet HAM and EF-HAMs regardless of the fiber thicknesses had a significantly lower Young's modulus, and hence, a higher elasticity compared with dry HAM and EF-HAMs. Biocompatibility analysis showed that the viability and migration rate of skeletal muscle cells on EF-HAMs were similar to control and HAM alone. Skeletal muscle cells seeded on HAM were shown to display random orientation, whereas cells on EF-HAM scaffolds were oriented along the alignment of the electrospun PLGA fibers. In summary, besides having good mechanical strength and elasticity, EF-HAM scaffold design decorated with aligned fiber topography holds a promising potential for use in the development of aligned tissue constructs.

Published
2018

5. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

Author

Alice S. Whittemore, Kunle Odunsi, Joe Dennis, Usha Menon, Agnieszka Dansonka-Mieszkowska, Angela Brooks-Wilson, Ingo B. Runnebaum, Melissa C. Southey, Bu-Tian Ji, Y. Ann Chen, Shashi Lele, Dong Liang, Jacek Gronwald, Keitaro Matsuo, Anna Jakubowska, Paul D.P. Pharoah, Lambertus A. Kiemeney, Andreas du Bois, Diether Lambrechts, Simon A. Gayther, Aleksandra Gentry-Maharaj, Brooke L. Fridley, Boon Kiong Lim, Kathryn L. Terry, Ira Schwaab, Jenny Chang-Claude, Mary Anne Rossing, Thilo Dörk, Kirsten B. Moysich, Satoyo Hosono, Rosalind Glasspool, Camilla Krakstad, Thomas A. Sellers, Douglas A. Levine, Estrid Høgdall, Yurii B. Shvetsov, Joellen M. Schildkraut, Douglas F. Easton, Philipp Harter, Francesmary Modugno, Ellen L. Goode, Karen Carty, John R. McLaughlin, Celeste Leigh Pearce, Alvaro N.A. Monteiro, Yu-Tang Gao, Arto Leminen, Peter A. Fasching, Kristine G. Wicklund, Maria Bisogna, Linda E. Kelemen, Sandrina Lambrechts, Edwin S. Iversen, Jennifer A. Doherty, Karen Lu, Robert P. Edwards, Elisa V. Bandera, Christine Walsh, Liisa M. Pelttari, Fiona Bruinsma, Iwona K. Rzepecka, Michelle A.T. Hildebrandt, Argyrios Ziogas, Soo-Hwang Teo, Susanne K. Kjaer, Lara E. Sucheston-Campbell, Nadeem Siddiqui, Hui-Yi Lin, Linda S. Cook, Julie M. Cunningham, Louise A. Brinton, Shelley S. Tworoger, Allan Jensen, Irene Orlow, Natalia Bogdanova, Helga B. Salvesen, Ralf Bützow, Steven A. Narod, Susan J. Ramus, Xifeng Wu, Anja Rudolph, Jolanta Kupryjanczyk, Nicolas Wentzensen, Clareann H. Bunker, Ganna Chornokur, Ed Dicks, Joseph H. Rothstein, Wei Zheng, Andrew Berchuck, Ignace Vergote, Lynne R. Wilkens, Ingvild L. Tangen, Beata Spiewankiewicz, Alice W. Lee, Yukie Bean, Peter Hillemanns, Lotte Ansgaard Thomsen, Leon F.A.G. Massuger, Valerie McGuire, Diana Eccles, Catherine M. Phelan, Yin Ling Woo, Patricia Harrington, Rachel Palmieri Weber, Evelyn Despierre, Hoda Anton-Culver, Anne M. van Altena, Eva S. Schernhammer, Ernest K. Amankwah, Ian G. Campbell, Jonathan Tyrer, Daniel W. Cramer, Matthias W. Beckmann, Shan Wang-Gohrke, Hannah P. Yang, Graham G. Giles, Lene Lundvall, Ian McNeish, Claus Høgdall, Elizabeth M. Poole, Roger L. Milne, Honglin Song, Hanis Nazihah Hasmad, Jan Lubinski, Ursula Eilber, Jenny Lester, Arif B. Ekici, Pamela J. Thompson, Harvey A. Risch, Kate Lawrenson, Malcolm C. Pike, Jennifer Permuth-Wey, Sandra Orsulic, Roberta B. Ness, James Paul, Robert A. Vierkant, Alexander Hein, Line Bjørge, Zhihua Chen, Marc T. Goodman, Melissa Kellar, Cezary Cybulski, Xiao-Ou Shu, Matthias Dürst, Barry P. Rosen, Heather S.L. Jim, Anna H. Wu, Natalia Antonenkova, Weiva Sieh, Tanja Pejovic, Florian Heitz, Beth Y. Karlan, Nhu D. Le, Heli Nevanlinna, Sara H. Olson, Jolanta Lissowska, and Katja K.H. Aben

Subjects
Oncology, medicine.medical_specialty, education.field_of_study, Epidemiology, Population, Single-nucleotide polymorphism, Genome-wide association study, Odds ratio, Biology, medicine.disease, Bioinformatics, Internal medicine, medicine, Carcinoma, Epithelial–mesenchymal transition, Ovarian cancer, Lung cancer, education, Genetics (clinical)
Abstract

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value

Published
2015

6. Genome-wide significant risk associations for mucinous ovarian carcinoma

Author

Jenny Lester, Arif B. Ekici, Xiao-Ou Shu, Georgia Chenevix-Trench, Julie M. Cunningham, Catherine M. Phelan, Tassja J. Spindler, Shelley S. Tworoger, Allan Jensen, Diana Eccles, Wei Zheng, Satoyo Hosono, Svend Aage Engelholm, Linda S. Cook, Thomas A. Sellers, John R. McLaughlin, Matthias W. Beckmann, Elizabeth M. Poole, Ignace Vergote, Francesmary Modugno, Jennifer A. Doherty, Sandrina Lambrechts, Lara Sucheston, Wang Gohrke Shan, Rosalind Glasspool, Barry P. Rosen, Pamela J. Thompson, Christine Walsh, Camilla Krakstad, Jennifer Permuth-Wey, Hoda Anton-Culver, Ralf Bützow, Ed Dicks, Yin Ling Woo, Honglin Song, Qiyuan Li, Leon F.A.G. Massuger, Yurii B. Shvetsov, Joellen M. Schildkraut, Xiaoqing Chen, Hannah P. Yang, Graham G. Giles, Sara H. Olson, Edwin S. Iversen, Claus Høgdall, Jacek Grownwald, Fiona Bruinsma, Peter Hillemanns, Iwona K. Rzepecka, Douglas T. Easton, Robert P. Edwards, Lynne R. Wilkens, Yukie Bean, Y. Ann Chen, Jonathan Tyrer, Tanja Pejovic, Patricia Harrington, Iain A. McNeish, Steven A. Narod, Joanna Moes-Sosnowska, Hanis Nazihah Hasmad, Ji-Heui Seo, Line Bjørge, Peter A. Fasching, Daniel W. Cramer, Florian Heitz, Beth Y. Karlan, Cezary Cybulski, Simon A. Gayther, Jolanta Kupryjanczyk, Nhu D. Le, Alexander Hein, Soo Hwang Teo, Nicolas Wentzensen, Valerie McGuire, Michelle A.T. Hildebrandt, Argyrios Ziogas, Heli Nevanlinna, Karen H. Lu, Diether Lambrechts, Kirsten B. Moysich, Jonathan Beesley, Kate Lawrenson, Ian G. Campbell, Andrew Berchuck, Philipp Harter, Lene Lundvall, Sandra Orsulic, Kathryn L. Terry, Jolanta Lissowska, Helen Baker, Matthew L. Freedman, Linda E. Kelemen, Maria Bisogna, Celeste Leigh Pearce, Ira Schwaab, Elisa V. Bandera, Kristine G. Wicklund, Arto Leminen, Nadeem Siddiqui, Joseph H. Rothstein, Melissa Kellar, Matthias Dürst, Harvey A. Risch, Włodzimierz Sawicki, Katja K.H. Aben, Alice S. Whittemore, Kunle Odunsi, Shashi Lele, Noor Azmi Mat Adenan, Susanne K. Kjaer, Robert A. Vierkant, Jan Lubinski, Natalia Bogdanova, Helga B. Salvesen, Anja Rudolph, Els Van Nieuwenhuysen, Irene Orlow, Joe Dennis, Ingvild L. Tangen, Estrid Høgdall, Alice W. Lee, Roberta B. Ness, James Paul, Malcolm C. Pike, Rachel Palmieri Weber, Anna H. Wu, Agnieszka Dansonka-Mieszkowska, Melissa C. Southey, Natalia Antonenkova, Anne M. van Altena, Xifeng Wu, Keitaro Matsuo, Anna Jakubowska, Paul D.P. Pharoah, Weiva Sieh, Lambertus A. Kiemeney, Lotte Nedergaard, Ursula Eilber, Janet M. Lee, Zhihua Chen, Andreas du Bois, Joseph L. Kelley, Aleksandra Gentry-Maharaj, Jenny Chang-Claude, Ellen L. Goode, Bu Tian Ji, Liisa M. Pelttari, Usha Menon, Dong Liang, Yu-Tang Gao, Brooke L. Fridley, Mary Anne Rossing, Thilo Dörk, Douglas A. Levine, Louise A. Brinton, Marc T. Goodman, Angela Brooks-Wilson, Ingo B. Runnebaum, Karen Carty, and Susan J. Ramus

Subjects
Green Fluorescent Proteins, Molecular Sequence Data, Quantitative Trait Loci, Single-nucleotide polymorphism, Genome-wide association study, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cell Line, Tumor, Ovarian carcinoma, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, 030304 developmental biology, Genetic association, Cell Nucleus, Homeodomain Proteins, Ovarian Neoplasms, 0303 health sciences, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, medicine.disease, Adenocarcinoma, Mucinous, Neoplasm Proteins, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, Gene Expression Regulation, Neoplastic, Microscopy, Fluorescence, Chromosomes, Human, Pair 2, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Expression quantitative trait loci, Cancer research, Adenocarcinoma, Female, Ovarian cancer, Genome-Wide Association Study
Abstract

Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Published
2015

7. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

Author

Francesmary Modugno, Alice S. Whittemore, Kunle Odunsi, Heli Nevanlinna, Fiona Bruinsma, Iwona K. Rzepecka, Jolanta Lissowska, Malcolm C. Pike, Bu-Tian Ji, Michelle A.T. Hildebrandt, Warren Davis, Agnieszka Dansonka-Mieszkowska, Line Bjørge, Roberta B. Ness, James Paul, Katja K.H. Aben, Nonna Kolomeyevskaya, Melissa C. Southey, Bridget Kruszka, Daniel W. Cramer, Shashikant Lele, Edwin S. Iversen, Kristina Schmitt, Julie M. Cunningham, Xifeng Wu, Celeste Leigh Pearce, Keitaro Matsuo, Cezary Cybulski, Linda E. Kelemen, Kirsten B. Moysich, Kristine G. Wicklund, Ralf Bützow, Shelley S. Tworoger, Grace Friel, Robert P. Edwards, Agnieszka Timorek, Leah Preus, Anna Jakubowska, Paul D.P. Pharoah, Karen Lu, Lambertus A. Kiemeney, Allan Jensen, Elisa V. Bandera, Steven A. Narod, Soo-Hwang Teo, Susanne K. Kjaer, Jonathan Tyrer, Joseph H. Rothstein, Irene Orlow, Rachel Palmieri Weber, Janine M. Joseph, Anna M. van Altena, Mary Nesline, Rüdiger Klapdor, Hannah P. Yang, Graham G. Giles, Pamela J. Thompson, Christine Walsh, Jolanta Kupryjanczyk, Wei Zheng, Nicolas Wentzensen, Angela Brooks-Wilson, Arto Leminen, Philipp Harter, Nadeem Siddiqui, Joanna Moes-Sosnowska, Yin Ling Woo, Anja Rudolph, John R. McLaughlin, Louise A. Brinton, Ingo B. Runnebaum, Shalaka S. Hampras, Linda S. Cook, Lotte Nedergaard, Lara E. Sucheston-Campbell, Natalia Bogdanova, Alexander Hein, Joseph L. Kelley, Claus Høgdall, Matthias Dürst, Jennifer A. Doherty, Ignace Vergote, Argyrios Ziogas, Ian G. Campbell, Prashant Singh, Hoda Anton-Culver, Shan Wang-Gohrke, Helga B. Salvesen, Stefan Nickels, Ingvild L. Tangen, Joe Dennis, Georgia Chenevix-Trench, Eva S. Schernhammer, Paul K. Wallace, Leon F.A.G. Massuger, Lynne R. Wilkens, Ed Dicks, Yukie Bean, Alice W. Lee, Ian McNeish, Evelyn Despierre, Patricia Harrington, Kevin H. Eng, Maria Bisogna, Nhu D. Le, Sandrina Lambrechts, Andrew Berchuck, Honglin Song, Hanis Nazihah Hasmad, Nils Schoof, Diana Eccles, Harvey A. Risch, Xiao-Ou Shu, Rosalind Glasspool, Peter Hillemanns, Jenny Permuth-Wey, Chi-Chen Hong, Catherine M. Phelan, Marc T. Goodman, Peter A. Fasching, Matthias W. Beckmann, Helen Baker, Doug Easton, Robert A. Vierkant, Barbara Perkins, Lene Lundvall, Elizabeth M. Poole, Joanna Plisiecka-Halasa, Arif B. Ekici, Melissa Kellar, Jan Lubinski, Alyssa Clay, Diether Lambrechts, Jacek Gronwald, Keith L. Knutson, Karen Carty, Camilla Krakstad, Jenny Lester, Simon A. Gayther, Ya-Yu Tsai, Rikki Cannioto, Kathryn L. Terry, Ira Schwaab, Susan J. Ramus, Andreas du Bois, Thomas A. Sellers, Estrid Høgdall, Valeria McGuire, Yurii B. Shvetsov, Joellen M. Schildkraut, Aleksandra Gentry-Maharaj, Jenny Chang-Claude, Sara H. Olson, Ellen L. Goode, Song Liu, Usha Menon, Dong Liang, Tanja Pejovic, Yu-Tang Gao, Florian Heitz, Beth Y. Karlan, Brooke L. Fridley, Mary Anne Rossing, Thilo Dörk, Douglas A. Levine, Weiva Sieh, Liisa M. Pelttari, Anna H. Wu, Natalia Antonenkova, Satoyo Hosono, Dennis, Joe [0000-0003-4591-1214], Dicks, Ed [0000-0002-0617-0401], Easton, Douglas [0000-0003-2444-3247], Song, Honglin [0000-0001-5076-7371], Tyrer, Jonathan [0000-0003-3724-4757], Pharoah, Paul [0000-0001-8494-732X], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, endocrine system diseases, Carcinoma, Ovarian Epithelial, T-Lymphocytes, Regulatory, 0302 clinical medicine, STAGE, Gene Frequency, Risk Factors, Genotype, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, education.field_of_study, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], immunosuppression, Middle Aged, Protein-Serine-Threonine Kinases, female genital diseases and pregnancy complications, 3. Good health, TGFBR2, Gene Expression Regulation, Neoplastic, Serous fluid, ovarian cancer, Oncology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Life Sciences & Biomedicine, EXPRESSION, Adult, CARCINOMA, Population, chemical and pharmacologic phenomena, Single-nucleotide polymorphism, FCGR2B, Protein Serine-Threonine Kinases, PERIPHERAL-BLOOD, Biology, DENDRITIC CELLS, Polymorphism, Single Nucleotide, 03 medical and health sciences, LUNG-CANCER, medicine, BREAST-CANCER, Humans, Genetic Predisposition to Disease, REGULATORY T-CELLS, education, Aged, Science & Technology, RECEPTOR, Receptor, Transforming Growth Factor-beta Type II, biomarkers, Cell Biology, medicine.disease, 030104 developmental biology, FC-GAMMA-RIIB, Immunology, genetic variation, Cancer research, Ovarian cancer, Receptors, Transforming Growth Factor beta, Clear cell, Priority Research Paper, Adenocarcinoma, Clear Cell
Abstract

Contains fulltext : 167177.pdf (Publisher’s version ) (Open Access) 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.

Published
2016

8. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

Author

Steven A. Narod, Beata Spiewankiewicz, Usha Menon, Tanja Pejovic, Dong Liang, Lynne R. Wilkens, Diana Eccles, Claus Høgdall, Florian Heitz, Beth Y. Karlan, John R. McLaughlin, Xiao-Ou Shu, Jennifer A. Doherty, Marc T. Goodman, Yu-Tang Gao, Brooke L. Fridley, Matthias W. Beckmann, Satoyo Hosono, Mary Anne Rossing, Elizabeth M. Poole, Thilo Dörk, Roger L. Milne, Douglas A. Levine, Arif B. Ekici, Francesmary Modugno, Hanis Nazihah Hasmad, Evelyn Despierre, Harvey A. Risch, Michelle A.T. Hildebrandt, Jenny Lester, Argyrios Ziogas, Arto Leminen, Sara H. Olson, Kate Lawrenson, Sandra Orsulic, Nadeem Siddiqui, Weiva Sieh, Ganna Chornokur, Ernest K. Amankwah, Natalia Bogdanova, Liisa M. Pelttari, Nhu D. Le, Lene Lundvall, Kirsten B. Moysich, Robert A. Vierkant, Helga B. Salvesen, Douglas F. Easton, Yin Ling Woo, Lotte Ansgaard Thomsen, Boon Kiong Lim, Philipp Harter, Hannah P. Yang, Graham G. Giles, Andrew Berchuck, Heather S.L. Jim, Anna H. Wu, Christine Walsh, Zhihua Chen, Alice S. Whittemore, Louise A. Brinton, Anne M. van Altena, Alice W. Lee, Fiona Bruinsma, Iwona K. Rzepecka, Natalia Antonenkova, Melissa Kellar, Jonathan Tyrer, Peter Hillemanns, Kunle Odunsi, Joe Dennis, Heli Nevanlinna, Alexander Hein, Catherine M. Phelan, Xifeng Wu, Jolanta Lissowska, Angela Brooks-Wilson, Ingo B. Runnebaum, Roberta B. Ness, James Paul, Linda S. Cook, Jacek Gronwald, Katja K.H. Aben, Agnieszka Dansonka-Mieszkowska, Melissa C. Southey, Linda E. Kelemen, Sandrina Lambrechts, Jan Lubinski, Leon F.A.G. Massuger, Karen Carty, Matthias Dürst, Ursula Eilber, Simon A. Gayther, Karen Lu, Bu-Tian Ji, Elisa V. Bandera, Shashi Lele, Keitaro Matsuo, Maria Bisogna, Anna Jakubowska, Paul D.P. Pharoah, Lambertus A. Kiemeney, Susan J. Ramus, Alvaro N.A. Monteiro, Edwin S. Iversen, Robert P. Edwards, Diether Lambrechts, Ellen L. Goode, Pamela J. Thompson, Ralf Bützow, Clareann H. Bunker, Jennifer Permuth-Wey, Anja Rudolph, Joseph H. Rothstein, Kathryn L. Terry, Ira Schwaab, Andreas du Bois, Aleksandra Gentry-Maharaj, Jolanta Kupryjanczyk, Nicolas Wentzensen, Ignace Vergote, Valerie McGuire, Jenny Chang-Claude, Ingvild L. Tangen, Ian G. Campbell, Daniel W. Cramer, Shan Wang-Gohrke, Peter A. Fasching, Rosalind Glasspool, Camilla Krakstad, Hoda Anton-Culver, Eva S. Schernhammer, Thomas A. Sellers, Lara E. Sucheston-Campbell, Estrid Høgdall, Yurii B. Shvetsov, Joellen M. Schildkraut, Honglin Song, Julie M. Cunningham, Shelley S. Tworoger, Allan Jensen, Ian McNeish, Wei Zheng, Barry P. Rosen, Malcolm C. Pike, Line Bjørge, Cezary Cybulski, Celeste Leigh Pearce, Kristine G. Wicklund, Soo-Hwang Teo, Susanne K. Kjaer, Hui-Yi Lin, Irene Orlow, Yukie Bean, Ann Y. Chen, and Rachel Palmieri Weber

Subjects
endocrine system, 0303 health sciences, media_common.quotation_subject, Single-nucleotide polymorphism, Biology, medicine.disease, Bioinformatics, Article, 03 medical and health sciences, PER3, 0302 clinical medicine, CSNK1E, 030220 oncology & carcinogenesis, Genotype, Genetic variation, Cancer research, medicine, Circadian rhythm, Ovarian cancer, Ovulation, 030304 developmental biology, media_common
Abstract

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10(-4)]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. ispartof: Journal of Genetics and Genome Research vol:2 issue:2 pages:017- ispartof: location:United States status: published

Published
2015

10. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

Author

Kate, Lawrenson, Edwin S, Iversen, Jonathan, Tyrer, Rachel Palmieri, Weber, Patrick, Concannon, Dennis J, Hazelett, Qiyuan, Li, Jeffrey R, Marks, Andrew, Berchuck, Janet M, Lee, Katja K H, Aben, Hoda, Anton-Culver, Natalia, Antonenkova, Elisa V, Bandera, Yukie, Bean, Matthias W, Beckmann, Maria, Bisogna, Line, Bjorge, Natalia, Bogdanova, Louise A, Brinton, Angela, Brooks-Wilson, Fiona, Bruinsma, Ralf, Butzow, Ian G, Campbell, Karen, Carty, Jenny, Chang-Claude, Georgia, Chenevix-Trench, Ann, Chen, Zhihua, Chen, Linda S, Cook, Daniel W, Cramer, Julie M, Cunningham, Cezary, Cybulski, Joanna, Plisiecka-Halasa, Joe, Dennis, Ed, Dicks, Jennifer A, Doherty, Thilo, Dörk, Andreas, du Bois, Diana, Eccles, Douglas T, Easton, Robert P, Edwards, Ursula, Eilber, Arif B, Ekici, Peter A, Fasching, Brooke L, Fridley, Yu-Tang, Gao, Aleksandra, Gentry-Maharaj, Graham G, Giles, Rosalind, Glasspool, Ellen L, Goode, Marc T, Goodman, Jacek, Gronwald, Philipp, Harter, Hanis Nazihah, Hasmad, Alexander, Hein, Florian, Heitz, Michelle A T, Hildebrandt, Peter, Hillemanns, Estrid, Hogdall, Claus, Hogdall, Satoyo, Hosono, Anna, Jakubowska, James, Paul, Allan, Jensen, Beth Y, Karlan, Susanne Kruger, Kjaer, Linda E, Kelemen, Melissa, Kellar, Joseph L, Kelley, Lambertus A, Kiemeney, Camilla, Krakstad, Diether, Lambrechts, Sandrina, Lambrechts, Nhu D, Le, Alice W, Lee, Rikki, Cannioto, Arto, Leminen, Jenny, Lester, Douglas A, Levine, Dong, Liang, Jolanta, Lissowska, Karen, Lu, Jan, Lubinski, Lene, Lundvall, Leon F A G, Massuger, Keitaro, Matsuo, Valerie, McGuire, John R, McLaughlin, Heli, Nevanlinna, Iain, McNeish, Usha, Menon, Francesmary, Modugno, Kirsten B, Moysich, Steven A, Narod, Lotte, Nedergaard, Roberta B, Ness, Mat Adenan, Noor Azmi, Kunle, Odunsi, Sara H, Olson, Irene, Orlow, Sandra, Orsulic, Celeste L, Pearce, Tanja, Pejovic, Liisa M, Pelttari, Jennifer, Permuth-Wey, Catherine M, Phelan, Malcolm C, Pike, Elizabeth M, Poole, Susan J, Ramus, Harvey A, Risch, Barry, Rosen, Mary Anne, Rossing, Joseph H, Rothstein, Anja, Rudolph, Ingo B, Runnebaum, Iwona K, Rzepecka, Helga B, Salvesen, Agnieszka, Budzilowska, Thomas A, Sellers, Xiao-Ou, Shu, Yurii B, Shvetsov, Nadeem, Siddiqui, Weiva, Sieh, Honglin, Song, Melissa C, Southey, Lara, Sucheston, Ingvild L, Tangen, Soo-Hwang, Teo, Kathryn L, Terry, Pamela J, Thompson, Agnieszka, Timorek, Shelley S, Tworoger, Els, Van Nieuwenhuysen, Ignace, Vergote, Robert A, Vierkant, Shan, Wang-Gohrke, Christine, Walsh, Nicolas, Wentzensen, Alice S, Whittemore, Kristine G, Wicklund, Lynne R, Wilkens, Yin-Ling, Woo, Xifeng, Wu, Anna H, Wu, Hannah, Yang, Wei, Zheng, Argyrios, Ziogas, Gerhard A, Coetzee, Matthew L, Freedman, Alvaro N A, Monteiro, Joanna, Moes-Sosnowska, Jolanta, Kupryjanczyk, Paul D, Pharoah, Simon A, Gayther, and Joellen M, Schildkraut

Subjects
Cancer Research, endocrine system diseases, Genome-wide association study, Carcinoma, Ovarian Epithelial, Risk Factors, Neoplasms, Ovarian Epithelial, 2.1 Biological and endogenous factors, Neoplasms, Glandular and Epithelial, Aetiology, skin and connective tissue diseases, Cancer, Genetics, Ovarian Neoplasms, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Glandular and Epithelial, General Medicine, Single Nucleotide, female genital diseases and pregnancy complications, Ovarian Cancer, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Female, Biotechnology, Australian Ovarian Cancer Study Group, Quantitative Trait Loci, Oncology and Carcinogenesis, Locus (genetics), Single-nucleotide polymorphism, Original Manuscript, Biology, Polymorphism, Single Nucleotide, Rare Diseases, Clinical Research, Australian Cancer Study, SNP, Humans, Genetic Predisposition to Disease, Genetic Testing, Oncology & Carcinogenesis, 1000 Genomes Project, Polymorphism, CHEK2, Genetic association, Prevention, Carcinoma, Human Genome, Checkpoint Kinase 2, Genetic Loci, Case-Control Studies, Cancer research, Imputation (genetics), Genome-Wide Association Study
Abstract

Contains fulltext : 152042.pdf (Publisher’s version ) (Closed access) Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P

Published
2015

11. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Author

Rosalind Glasspool, Lynne R. Wilkens, Camilla Krakstad, Diana Eccles, Liisa M. Pelttari, Thomas A. Sellers, Anja Rudolph, Estrid Høgdall, Yurii B. Shvetsov, Matthias W. Beckmann, Ignace Vergote, Angela Brooks-Wilson, Ingo B. Runnebaum, Joellen M. Schildkraut, Joe Dennis, Ingvild L. Tangen, Elizabeth M. Poole, Arif B. Ekici, Xiao-Ou Shu, Alice S. Whittemore, Valerie McGuire, Kunle Odunsi, Agnieszka Dansonka-Mieszkowska, Melissa C. Southey, Keitaro Matsuo, Anna Jakubowska, Paul D.P. Pharoah, Lambertus A. Kiemeney, Douglas T. Easton, Simon A. Gayther, Anna deFazio, Ian G. Campbell, Hanis Nazihah Hasmad, Shashi Lele, Maria Bisogna, Zhihua Chen, Usha Menon, Jenny Lester, Ursula Eilber, Iwona K. Rzepecka, Shan Wang-Gohrke, Steven A. Narod, Qiyuan Li, Dong Liang, Jonathan Tyrer, Kate Lawrenson, Hoda Anton-Culver, Alvaro N.A. Monteiro, Ed Dicks, Lene Lundvall, Sandra Orsulic, Brooke L. Fridley, Ellen L. Goode, Linda E. Kelemen, Edwin S. Iversen, Ya Yu Tsai, Mary Anne Rossing, Karen Carty, Thilo Dörk, Penelope M. Webb, Yukie Bean, Matthias Dürst, Soo Hwang Teo, Claus Høgdall, Robert P. Edwards, Alison M. Karst, Yu-Tang Gao, Harvey A. Risch, Patricia Harrington, Daniel W. Cramer, Ji-Heui Seo, Douglas A. Levine, Christine Walsh, Karen Lu, Elisa V. Bandera, Louise A. Brinton, Satoyo Hosono, Hannah P. Yang, Graham G. Giles, Robert A. Vierkant, Argyrios Ziogas, Honglin Song, Ian McNeish, Anne M. van Altena, Tanja Pejovic, Florian Heitz, Beth Y. Karlan, Kirsten B. Moysich, Philipp Harter, Joseph L. Kelley, Andrew Berchuck, Paul A. James, Peter Hillemanns, Susan J. Ramus, Jacek Grownwald, Celeste Leigh Pearce, Ronny Drapkin, Kristine G. Wicklund, Mat Adenan Noor Azmi, Lara Sucheston, Alexander Hein, Jolanta Kupryjanczyk, Ralf Bützow, Georgia Chenevix-Trench, Michelle A.T. Hildebrandt, Francesmary Modugno, John R. McLaughlin, Arto Leminen, Nicolas Wentzensen, Siddhartha Kar, Sara H. Olson, Susanne K. Kjaer, Barry P. Rosen, Andreas du Bois, Linda S. Cook, Jennifer A. Doherty, Joseph H. Rothstein, Aleksandra Gentry-Maharaj, Julie M. Cunningham, Leon F.A.G. Massuger, Irene Orlow, Rachel Palmieri Weber, Pamela J. Thompson, Tassja J. Spindler, Jenny Chang-Claude, Jennifer Permuth-Wey, Catherine M. Phelan, Yi-Bu Chen, Bu Tian Ji, Heli Nevanlinna, Roberta B. Ness, Shelley S. Tworoger, Allan Jensen, Anna H. Wu, Malcolm C. Pike, Fiona Bruinsma, Line Bjørge, Jolanta Lissowska, Natalia Antonenkova, Cezary Cybulski, Wei Zheng, Lotte Nedergaard, Els Van Nieuwenhuysen, Anne Chen, Janet M. Lee, David D.L. Bowtell, Helen Baker, Katja K.H. Aben, Xifeng Wu, Melissa Kellar, Weiva Sieh, Nhu D. Le, Marc T. Goodman, Matthew L. Freedman, Yin Ling Woo, Sandrina Lambrechts, Peter A. Fasching, Diether Lambrechts, Kathryn L. Terry, Ira Schwaab, Jan Lubinski, Natalia Bogdanova, Helga B. Salvesen, Alice W. Lee, Agnieszka Timorek, Nadeem Siddiqui, Department of Pathology, Medicum, Department of Obstetrics and Gynecology, Clinicum, and HUS Gynecology and Obstetrics

Subjects
EXPRESSION, Quantitative Trait Loci, General Physics and Astronomy, Locus (genetics), Genome-wide association study, Quantitative trait locus, Biology, Carcinoma, Ovarian Epithelial, VARIANTS, ANALYSES REVEAL, BREAST, General Biochemistry, Genetics and Molecular Biology, Article, Nuchal Cord, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Cell Line, Tumor, Genetic predisposition, SNP, Humans, Genetic Predisposition to Disease, Neoplasms, Glandular and Epithelial, GENOME-WIDE ASSOCIATION, Genetic Association Studies, 030304 developmental biology, Genetic association, Genetics, Homeodomain Proteins, Ovarian Neoplasms, 0303 health sciences, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, LONG-RANGE INTERACTION, IDENTIFICATION, General Chemistry, RISK LOCI, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, FALLOPIAN-TUBE, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Expression quantitative trait loci, Female, 3111 Biomedicine, HOX GENES, Protein Binding
Abstract

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, Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Published
2015

12. Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients

Author

Melissa C. Southey, Wei Xiong Wen, Eswary Thirthagiri, Daniel J. Park, Hanis Nazihah Hasmad, Peter Choon Eng Kang, Mahirah Ma'som, Yin Ling Woo, Tu Nguyen-Dumont, Boon Kiong Lim, Soo Hwang Teo, and Kah Nyin Lai

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, endocrine system diseases, PALB2, Genetic counseling, DNA Mutational Analysis, Genes, BRCA2, Genes, BRCA1, Carcinoma, Ovarian Epithelial, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Asian People, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Neoplasms, Glandular and Epithelial, Family history, skin and connective tissue diseases, Germ-Line Mutation, Genetic testing, Gynecology, BRCA2 Protein, Ovarian Neoplasms, medicine.diagnostic_test, business.industry, BRCA1 Protein, Obstetrics and Gynecology, Cancer, medicine.disease, Genes, p53, Penetrance, female genital diseases and pregnancy complications, 030104 developmental biology, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Female, Tumor Suppressor Protein p53, Ovarian cancer, business
Abstract

Objective Despite the discovery of breast and ovarian cancer predisposition genes BRCA1 and BRCA2 more than two decades ago, almost all the available data relate to women of European ancestry, with only a handful of studies in Asian populations. In this study, we determined the frequency of germline alterations in BRCA1 and BRCA2 in ovarian cancer patients from a multi-ethnic cross-sectional cohort of Asian ovarian cancer patients from Malaysia. Methods From October 2008 to February 2015, we established a hospital-based cohort of ovarian cancer patients and the germline status of all 218 women with invasive epithelial ovarian cancer was tested using targeted amplification and sequencing of the intron–exon junctions and exonic sequences of BRCA1 , BRCA2 , PALB2 and TP53. Results BRCA1 and BRCA2 mutations were found in 8% (17 cases) and 3% (7 cases) of the ovarian cancer patients, respectively. Mutation carriers were diagnosed at a similar age to non-carriers, but were more likely to be Indian, have serous ovarian cancer, and have more relatives with breast or ovarian cancer. Nonetheless, 42% (10/24) of mutation carriers did not have any family history of breast or ovarian cancer and offering genetic counselling and genetic testing only to women with family history would mean that 35% (6/17) of BRCA1 mutation carriers and 57% (4/7) of BRCA2 mutation carriers would not be offered genetic testing. Conclusions Our data suggest that, similar to Caucasians, a significant proportion of Asian ovarian cancer was attributed to germline mutations in BRCA1 and to a lesser extent in BRCA2 .

Published
2015

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