Search

Your search keyword '"Pathak, Harsh"' showing total 188 results
Start Over Author "Pathak, Harsh" Search Limiters Full Text
188 results on '"Pathak, Harsh"'

1. Rethinking the Relationship between Recurrent and Non-Recurrent Neural Networks: A Study in Sparsity

Author

Hershey, Quincy, Paffenroth, Randy, Pathak, Harsh, and Tavener, Simon

Subjects
Computer Science - Machine Learning
Abstract

Neural networks (NN) can be divided into two broad categories, recurrent and non-recurrent. Both types of neural networks are popular and extensively studied, but they are often treated as distinct families of machine learning algorithms. In this position paper, we argue that there is a closer relationship between these two types of neural networks than is normally appreciated. We show that many common neural network models, such as Recurrent Neural Networks (RNN), Multi-Layer Perceptrons (MLP), and even deep multi-layer transformers, can all be represented as iterative maps. The close relationship between RNNs and other types of NNs should not be surprising. In particular, RNNs are known to be Turing complete, and therefore capable of representing any computable function (such as any other types of NNs), but herein we argue that the relationship runs deeper and is more practical than this. For example, RNNs are often thought to be more difficult to train than other types of NNs, with RNNs being plagued by issues such as vanishing or exploding gradients. However, as we demonstrate in this paper, MLPs, RNNs, and many other NNs lie on a continuum, and this perspective leads to several insights that illuminate both theoretical and practical aspects of NNs.

Published
2024

2. Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort

Author

Saeed, Anwaar, Park, Robin, Pathak, Harsh, Al-Bzour, Ayah Nedal, Dai, Junqiang, Phadnis, Milind, Al-Rajabi, Raed, Kasi, Anup, Baranda, Joaquina, Sun, Weijing, Williamson, Stephen, Chiu, Yu-Chiao, Osmanbeyoglu, Hatice Ulku, Madan, Rashna, Abushukair, Hassan, Mulvaney, Kelly, Godwin, Andrew K., and Saeed, Azhar

Published
2024
Full Text
View/download PDF

5. A window of opportunity trial evaluating intratumoral injection of Copaxone® in patients with percutaneously accessible tumors

Author

Baranda, Joaquina C., Mohyuddin, Ghulam Rehman, Bur, Andrés M., Shnayder, Yelizaveta, Sweeney, Kyle R., Kakarala, Kiran, Prouty, Megan, Pathak, Harsh, Puri, Rajni, Mitra, Amrita, Madan, Rashna, Forrest, M. Laird, Huang, Aric, Weir, Scott, Godwin, Andrew K., Alhakamy, Nabil A., Griffin, J. Daniel, and Berkland, Cory J.

Published
2023
Full Text
View/download PDF

7. Efficient Super Resolution For Large-Scale Images Using Attentional GAN

Author

Pathak, Harsh Nilesh, Li, Xinxin, Minaee, Shervin, and Cowan, Brooke

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Single Image Super Resolution (SISR) is a well-researched problem with broad commercial relevance. However, most of the SISR literature focuses on small-size images under 500px, whereas business needs can mandate the generation of very high resolution images. At Expedia Group, we were tasked with generating images of at least 2000px for display on the website, four times greater than the sizes typically reported in the literature. This requirement poses a challenge that state-of-the-art models, validated on small images, have not been proven to handle. In this paper, we investigate solutions to the problem of generating high-quality images for large-scale super resolution in a commercial setting. We find that training a generative adversarial network (GAN) with attention from scratch using a large-scale lodging image data set generates images with high PSNR and SSIM scores. We describe a novel attentional SISR model for large-scale images, A-SRGAN, that uses a Flexible Self Attention layer to enable processing of large-scale images. We also describe a distributed algorithm which speeds up training by around a factor of five., Comment: Accepted by IEEE International Conference on Big Data, 2018

Published
2018

8. Drug discovery using clinical outcome-based Connectivity Mapping: application to ovarian cancer

Author

Raghavan, Rama, Hyter, Stephen, Pathak, Harsh B, Godwin, Andrew K, Konecny, Gottfried, Wang, Chen, Goode, Ellen L, and Fridley, Brooke L

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Orphan Drug, Genetics, Ovarian Cancer, Rare Diseases, Biotechnology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Antineoplastic Agents, Cell Line, Tumor, Computational Biology, Databases, Genetic, Disease Progression, Dose-Response Relationship, Drug, Drug Discovery, Drug Screening Assays, Antitumor, Female, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Staging, Ovarian Neoplasms, Proportional Hazards Models, Recurrence, Gene expression signature, Time to recurrence, Bioinformatics, Connectivity Mapping, Drug discovery, Ovarian cancer, Biological Sciences, Information and Computing Sciences, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundEpithelial ovarian cancer (EOC) is the fifth leading cause of cancer death among women in the United States (5 % of cancer deaths). The standard treatment for patients with advanced EOC is initial debulking surgery followed by carboplatin-paclitaxel combination chemotherapy. Unfortunately, with chemotherapy most patients relapse and die resulting in a five-year overall survival around 45 %. Thus, finding novel therapeutics for treating EOC is essential. Connectivity Mapping (CMAP) has been used widely in cancer drug discovery and generally has relied on cancer cell line gene expression and drug phenotype data. Therefore, we took a CMAP approach based on tumor information and clinical endpoints from high grade serous EOC patients.MethodsWe determined tumor gene expression signatures (e.g., sets of genes) associated with time to recurrence (with and without adjustment for additional clinical covariates) among patients within TCGA (n = 407) and, separately, from the Mayo Clinic (n = 326). Each gene signature was inputted into CMAP software (Broad Institute) to determine a set of drugs for which our signature "matches" the "reference" signature, and drugs that overlapped between the CMAP analyses and the two studies were carried forward for validation studies involving drug screens on a set of 10 EOC cell lines.ResultsOf the 11 drugs carried forward, five (mitoxantrone, podophyllotoxin, wortmannin, doxorubicin, and 17-AAG) were known a priori to be cytotoxics and were indeed shown to effect EOC cell viability.ConclusionsFuture research is needed to investigate the use of these CMAP and similar analyses for determining combination therapies that might work synergistically to kill cancer cells and to apply this in silico bioinformatics approach using clinical outcomes to other cancer drug screening studies.

Published
2016

9. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

Author

Rebbeck, Timothy R, Mitra, Nandita, Wan, Fei, Sinilnikova, Olga M, Healey, Sue, McGuffog, Lesley, Mazoyer, Sylvie, Chenevix-Trench, Georgia, Easton, Douglas F, Antoniou, Antonis C, Nathanson, Katherine L, CIMBA Consortium, Laitman, Yael, Kushnir, Anya, Paluch-Shimon, Shani, Berger, Raanan, Zidan, Jamal, Friedman, Eitan, Ehrencrona, Hans, Stenmark-Askmalm, Marie, Einbeigi, Zakaria, Loman, Niklas, Harbst, Katja, Rantala, Johanna, Melin, Beatrice, Huo, Dezheng, Olopade, Olufunmilayo I, Seldon, Joyce, Ganz, Patricia A, Nussbaum, Robert L, Chan, Salina B, Odunsi, Kunle, Gayther, Simon A, Domchek, Susan M, Arun, Banu K, Lu, Karen H, Mitchell, Gillian, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Godwin, Andrew K, Pathak, Harsh, Ross, Eric, Daly, Mary B, Whittemore, Alice S, John, Esther M, Miron, Alexander, Terry, Mary Beth, Chung, Wendy K, Goldgar, David E, Buys, Saundra S, Janavicius, Ramunas, Tihomirova, Laima, Tung, Nadine, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Steele, Linda, Neuhausen, Susan L, Ding, Yuan Chun, Ejlertsen, Bent, Gerdes, Anne-Marie, Hansen, Thomas VO, Ramón y Cajal, Teresa, Osorio, Ana, Benitez, Javier, Godino, Javier, Tejada, Maria-Isabel, Duran, Mercedes, Weitzel, Jeffrey N, Bobolis, Kristie A, Sand, Sharon R, Fontaine, Annette, Savarese, Antonella, Pasini, Barbara, Peissel, Bernard, Bonanni, Bernardo, Zaffaroni, Daniela, Vignolo-Lutati, Francesca, Scuvera, Giulietta, Giannini, Giuseppe, Bernard, Loris, Genuardi, Maurizio, Radice, Paolo, Dolcetti, Riccardo, Manoukian, Siranoush, Pensotti, Valeria, Gismondi, Viviana, Yannoukakos, Drakoulis, Fostira, Florentia, Garber, Judy, Torres, Diana, Rashid, Muhammad Usman, Hamann, Ute, Peock, Susan, Frost, Debra, Platte, Radka, Evans, D Gareth, Eeles, Rosalind, Davidson, Rosemarie, and Eccles, Diana

Subjects
CIMBA Consortium, Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, Nucleotides, Risk Factors, Age of Onset, Heterozygote, Mutation, Genes, BRCA1, Genes, BRCA2, Adult, Middle Aged, Female, Cancer, Prevention, Rare Diseases, Breast Cancer, Clinical Research, Ovarian Cancer, General & Internal Medicine, Medical and Health Sciences
Abstract

ImportanceLimited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.ObjectiveTo identify mutation-specific cancer risks for carriers of BRCA1/2.Design, setting, and participantsObservational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.ExposuresMutations of BRCA1 or BRCA2.Main outcomes and measuresBreast and ovarian cancer risks.ResultsAmong BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.Conclusions and relevanceBreast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Published
2015

11. Circulating Tumor Cell Subpopulations Predict Treatment Outcome in Pancreatic Ductal Adenocarcinoma (PDAC) Patients

Author

Freed, Ian M., primary, Kasi, Anup, additional, Fateru, Oluwadamilola, additional, Hu, Mengjia, additional, Gonzalez, Phasin, additional, Weatherington, Nyla, additional, Pathak, Harsh, additional, Hyter, Stephen, additional, Sun, Weijing, additional, Al-Rajabi, Raed, additional, Baranda, Joaquina, additional, Hupert, Mateusz L., additional, Chalise, Prabhakar, additional, Godwin, Andrew K., additional, A. Witek, Malgorzata, additional, and Soper, Steven A., additional

Published
2023
Full Text
View/download PDF

12. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

Author

Siddiq, Afshan, Couch, Fergus J, Chen, Gary K, Lindström, Sara, Eccles, Diana, Millikan, Robert C, Michailidou, Kyriaki, Stram, Daniel O, Beckmann, Lars, Rhie, Suhn Kyong, Ambrosone, Christine B, Aittomäki, Kristiina, Amiano, Pilar, Apicella, Carmel, Investigators, Australian Breast Cancer Tissue Bank, Baglietto, Laura, Bandera, Elisa V, Beckmann, Matthias W, Berg, Christine D, Bernstein, Leslie, Blomqvist, Carl, Brauch, Hiltrud, Brinton, Louise, Bui, Quang M, Buring, Julie E, Buys, Saundra S, Campa, Daniele, Carpenter, Jane E, Chasman, Daniel I, Chang-Claude, Jenny, Chen, Constance, Clavel-Chapelon, Françoise, Cox, Angela, Cross, Simon S, Czene, Kamila, Deming, Sandra L, Diasio, Robert B, Diver, W Ryan, Dunning, Alison M, Durcan, Lorraine, Ekici, Arif B, Fasching, Peter A, Study, Familial Breast Cancer, Feigelson, Heather Spencer, Fejerman, Laura, Figueroa, Jonine D, Fletcher, Olivia, Flesch-Janys, Dieter, Gaudet, Mia M, Consortium, The GENICA, Gerty, Susan M, Rodriguez-Gil, Jorge L, Giles, Graham G, van Gils, Carla H, Godwin, Andrew K, Graham, Nikki, Greco, Dario, Hall, Per, Hankinson, Susan E, Hartmann, Arndt, Hein, Rebecca, Heinz, Judith, Hoover, Robert N, Hopper, John L, Hu, Jennifer J, Huntsman, Scott, Ingles, Sue A, Irwanto, Astrid, Isaacs, Claudine, Jacobs, Kevin B, John, Esther M, Justenhoven, Christina, Kaaks, Rudolf, Kolonel, Laurence N, Coetzee, Gerhard A, Lathrop, Mark, Le Marchand, Loic, Lee, Adam M, Lee, I-Min, Lesnick, Timothy, Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Martin, Nicholas G, McLean, Catriona A, Meijers-Heijboer, Hanne, Meindl, Alfons, Miron, Penelope, Monroe, Kristine R, Montgomery, Grant W, Müller-Myhsok, Bertram, Nickels, Stefan, Nyante, Sarah J, Olswold, Curtis, Overvad, Kim, Palli, Domenico, Park, Daniel J, Palmer, Julie R, and Pathak, Harsh

Subjects
Biological Sciences, Genetics, Clinical Research, Aging, Human Genome, Breast Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Australian Breast Cancer Tissue Bank Investigators, Familial Breast Cancer Study, GENICA Consortium, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

Published
2012

14. Cyber Security in Power System: Challenges and Opportunities

Author

Mohit Kumar Maheshwari, Anurag Kumar Gupta, Pathak, Harsh Kumar, Khan, Hera, and Maurya, Arun Kumar

Subjects
Cyber security, PLC, SCADA, PHP device
Abstract

Modern power grids are not isolated from the outside world – disturbance on any system or in any component can cause instability or even blackout in the case of a power grid [ because all components of the control system of the power grid are not isolated is lords, they all are interconnected]. Cyber-attacks on the power grid could result in significant economic losses. In the present scenario, in Russia -Ukraine war, Russia wanted to destroy Ukraine's power grid system to break its energy supply and make the war easier for them. This power describes the power grid, Cyber security, Architecture of the power grid, Details about the Indian power grid present era of digital technologies, Requirements from cyber security for a power grid, and Type of cyber-attacks that could occur in our security scheme. Here we present a PV cell-based power grid model also to give you a clear view of the power grid. The short form we use in this paper: -PHP device (Hypertext processor), ASP (Active sensor page), OT system (Operational Technologies system), IT system (Information Technology System), PX data (Plotty Express), AMR system (Automated Meter Reading system), REMC (Renewable Energy Management Center), SCADA (Supervisory Control and Data Acquisition)., {"references":["1.\tMaurya, A. K., Rai, A. K., & Ahuja, H. (2022). Performance Analysis of a 40kWp Grid Connected Solar PV System in Northern India. Journal of Research and Advancement in Electrical Engineering, 4(3).","2.\tYe, J., Guo, L., Yang, B., Li, F., Du, L., Guan, L., & Song, W. (2020). Cyber–physical security of powertrain systems in modern electric vehicles: Vulnerabilities, challenges, and future visions. IEEE Journal of Emerging and Selected Topics in Power Electronics, 9(4), 4639-4657.","3.\tMaurya, A. K., Rai, A. K., & Ahuja, H. (2022, December). Comparative Analysis of Different MPPT Algorithms for Roof-Top Solar PV System. In 2022 International Conference on Automation, Computing and Renewable Systems (ICACRS) (pp. 1412-1417). IEEE.","4.\tBhattacharya, S., Saini, D., & Singh, N. Internet of Things (IoT) in smart cities: A review. In 2017 2nd International Conference for Convergence in Technology (I2CT) (pp. 386-391) IEEE, 2017.","5.\tMaurya, A. K., Tyagi, Y., Khan, H., Narang, D., & Ahuja, H. (2022, December). Components & Control Scheme used for Line of Sight Stabilization in Defence Applications. In 2022 International Conference on Automation, Computing and Renewable Systems (ICACRS) (pp. 1425-1431). IEEE.","6.\tCaragliu, A., Del Bo, C., & Nijkamp, P. (2009). Smart cities in Europe. Research Memoranda Series 0048 (VU University Amsterdam, Faculty of Economics, Business Administration and Econometrics). J. Urban Technol, 18.","7.\tMaurya, A. K., Khan, H., Rai, A. K., & Ahuja, H. (2022, December). Load Frequency Control by using Different Controllers in Multi-Area Power System Networks. In 2022 International Conference on Automation, Computing and Renewable Systems (ICACRS) (pp. 1418-1424). IEEE.","8.\tTschorsch, F., & Scheuermann, B. (2013). An algorithm for privacy-preserving distributed user statistics. Computer Networks, 57(14), 2775-2787.","9.\tMaurya, A. K., & Khan, H. (2022). Converters' Topologies & Experimental Characteristics of Roof-top Solar PV System: A Comparative Analysis. Advancement and Research in Instrumentation Engineering, 5(3).","10.\tGubbi, J., Buyya, R., Marusic, S., & Palaniswami, M. (2013). Internet of Things (IoT): A vision, architectural elements, and future directions. Future generation computer systems, 29(7), 1645-1660."]}

Published
2023
Full Text
View/download PDF

15. Abstract 5334: Targeting the KIF15-TPX2 PPI to overcome KIF11 inhibitor resistance in epithelial ovarian cancer

Author

Gibbs, Benjamin K., primary, Douglas, Justin T., additional, Wates, Rebecca J., additional, McDonald, Peter R., additional, Whitaker, Amy M., additional, Ndi, Cornelius N., additional, Pathak, Harsh B., additional, Harned, Laurie A., additional, Neuenswander, Sarah A., additional, Broward, Melinda A., additional, Freudenthal, Bret D., additional, Roy, Anuradha, additional, Schoenen, Frank J., additional, and Godwin, Andrew K., additional

Published
2023
Full Text
View/download PDF

17. Proteomic Profiling of Fallopian Tube-Derived Extracellular Vesicles Using a Microfluidic Tissue-on-Chip System

Author

Zha, Didi, primary, Rayamajhi, Sagar, additional, Sipes, Jared, additional, Russo, Angela, additional, Pathak, Harsh B., additional, Li, Kailiang, additional, Sardiu, Mihaela E., additional, Bantis, Leonidas E., additional, Mitra, Amrita, additional, Puri, Rajni V., additional, Trinidad, Camille V., additional, Cain, Brian P., additional, Isenberg, Brett C., additional, Coppeta, Jonathan, additional, MacLaughlan, Shannon, additional, Godwin, Andrew K., additional, and Burdette, Joanna E., additional

Published
2023
Full Text
View/download PDF

18. First-Line Immunotherapy with Check-Point Inhibitors: Prospective Assessment of Cognitive Function

Author

Myers, Jamie S., primary, Parks, Adam C., additional, Mahnken, Jonathan D., additional, Young, Kate J., additional, Pathak, Harsh B., additional, Puri, Rajni V., additional, Unrein, Amber, additional, Switzer, Phyllis, additional, Abdulateef, Yazan, additional, Sullivan, Samantha, additional, Walker, John F., additional, Streeter, David, additional, and Burns, Jeffrey M., additional

Published
2023
Full Text
View/download PDF

19. Microfluidic affinity selection of active SARS-CoV-2 virus particles

Author

Gamage, Sachindra S. T., primary, Pahattuge, Thilanga N., additional, Wijerathne, Harshani, additional, Childers, Katie, additional, Vaidyanathan, Swarnagowri, additional, Athapattu, Uditha S., additional, Zhang, Lulu, additional, Zhao, Zheng, additional, Hupert, Mateusz L., additional, Muller, Rolf M., additional, Muller-Cohn, Judy, additional, Dickerson, Janet, additional, Dufek, Dylan, additional, Geisbrecht, Brian V., additional, Pathak, Harsh, additional, Pessetto, Ziyan, additional, Gan, Gregory N., additional, Choi, Junseo, additional, Park, Sunggook, additional, Godwin, Andrew K., additional, Witek, Malgorzata A., additional, and Soper, Steven A., additional

Published
2022
Full Text
View/download PDF

22. Abstract 5306: IRAK1: A novel TOLLway to target ovarian cancer

Author

Standing, David, primary, Gunewardena, Sumedha, additional, Sayed, Afreen A., additional, Pritchard, Michele T., additional, Pathak, Harsh B., additional, Godwin, Andrew K., additional, Petersen, Shariska, additional, Khabele, Dineo, additional, Roy, Jensen A., additional, Dandawate, Prasad, additional, Weir, Scott J., additional, and Anant, Shrikant, additional

Published
2022
Full Text
View/download PDF

23. Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal

Author

Chugh, Rishi Man, primary, Bhanja, Payel, additional, Olea, Ximena Diaz, additional, Tao, Fang, additional, Schroeder, Kealan, additional, Zitter, Ryan, additional, Arora, Tanu, additional, Pathak, Harsh, additional, Kimler, Bruce F., additional, Godwin, Andrew K., additional, Perry, John M., additional, and Saha, Subhrajit, additional

Published
2022
Full Text
View/download PDF

24. Altered Intestinal Permeability Biomarkers in Schizophrenia: A Possible Link with Subclinical Inflammation

Author

Gokulakrishnan, Kuppan, primary, Nikhil, Joyappa, additional, VS, Sreeraj, additional, Holla, Bharath, additional, Thirumoorthy, Chinnasamy, additional, Sandhya, Narasimhan, additional, Nichenametla, Sonika, additional, Pathak, Harsh, additional, Shivakumar, Venkataram, additional, Debnath, Monojit, additional, Venkatasubramanian, Ganesan, additional, and Varambally, Shivarama, additional

Published
2022
Full Text
View/download PDF

25. Abstract P2-01-05: Impact of post-treatment ctDNA and residual cancer burden (RCB) on outcomes in patients with triple-negative breast cancer (TNBC) and residual disease

Author

Sharma, Priyanka, primary, Stecklein, Shane R, additional, Kimler, Bruce F, additional, Yoder, Rachel, additional, Schwensen, Kelsey, additional, Staley, Joshua M, additional, Khan, Qamar J, additional, O'Dea, Anne P, additional, Nye, Lauren E, additional, Elia, Manana, additional, Heldstab, Jaimie, additional, Home, Trisha, additional, Hyter, Stephen, additional, Isakova, Kamilla, additional, Pathak, Harsh B, additional, and Godwin, Andrew K, additional

Published
2022
Full Text
View/download PDF

26. sj-docx-1-bmi-10.1177_11772719221132693 – Supplemental material for MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation

Author

Crow, Jennifer, Samuel, Glenson, Farrow, Emily, Gibson, Margaret, Johnston, Jefferey, Guest, Erin, Miller, Neil, Pei, Dong, Koestler, Devin, Pathak, Harsh, Liang, Xiaobo, Mangels, Cooper, and Godwin, Andrew K

Subjects
Biochemistry
Abstract

Supplemental material, sj-docx-1-bmi-10.1177_11772719221132693 for MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation by Jennifer Crow, Glenson Samuel, Emily Farrow, Margaret Gibson, Jefferey Johnston, Erin Guest, Neil Miller, Dong Pei, Devin Koestler, Harsh Pathak, Xiaobo Liang, Cooper Mangels and Andrew K Godwin in Biomarker Insights

Published
2022
Full Text
View/download PDF

28. MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation

Author

Crow, Jennifer, primary, Samuel, Glenson, additional, Farrow, Emily, additional, Gibson, Margaret, additional, Johnston, Jefferey, additional, Guest, Erin, additional, Miller, Neil, additional, Pei, Dong, additional, Koestler, Devin, additional, Pathak, Harsh, additional, Liang, Xiaobo, additional, Mangels, Cooper, additional, and Godwin, Andrew K, additional

Published
2022
Full Text
View/download PDF

29. Concurrent conventional & high-definition transcranial direct current stimulation for treatment of schizophrenia with co-morbid obsessive-compulsive disorder: A case report

Author

Nayok, Swarna Buddha, primary, Pathak, Harsh, additional, Suhas, Satish, additional, Thimmashetty, Vani H., additional, Shivaprakash, Prakrithi, additional, Madhu Sudhan, Ragibommanahalli M., additional, Sreeraj, Vanteemar S., additional, Narayanaswamy, Janardhanan C., additional, and Venkatasubramanian, Ganesan, additional

Published
2021
Full Text
View/download PDF

30. Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer

Author

Sharma, Priyanka, primary, Abramson, Vandana G., additional, O'Dea, Anne, additional, Nye, Lauren, additional, Mayer, Ingrid, additional, Pathak, Harsh B., additional, Hoffmann, Marc, additional, Stecklein, Shane R., additional, Elia, Manana, additional, Lewis, Sharon, additional, Scott, Jecinta, additional, De Jong, Jilliann A., additional, Wang, Yen Y., additional, Yoder, Rachel, additional, Schwensen, Kelsey, additional, Finke, Karissa, additional, Heldstab, Jaimie, additional, LaFaver, Stephanie, additional, Williamson, Stephen K., additional, Phadnis, Milind A., additional, Reed, Gregory A., additional, Kimler, Bruce F., additional, Khan, Qamar J., additional, and Godwin, Andrew K., additional

Published
2021
Full Text
View/download PDF

31. WJMSC‐derived small extracellular vesicle enhance T cell suppression through PD‐L1

Author

Li, Meizhang, primary, Soder, Rupal, additional, Abhyankar, Sunil, additional, Abdelhakim, Haitham, additional, Braun, Mitchell W., additional, Trinidad, Camille V., additional, Pathak, Harsh B., additional, Pessetto, Ziyan, additional, Deighan, Clayton, additional, Ganguly, Siddhartha, additional, Dawn, Buddhadeb, additional, McGuirk, Joseph, additional, Dunavin, Neil, additional, and Godwin, Andrew K., additional

Published
2021
Full Text
View/download PDF

36. 54 - Immunogenicity of Sars-Cov-2 Vaccination in Hematopoietic Stem Cell Transplant and Chimeric Antigen Receptor T-Cell Therapy Recipients

Author

Mushtaq, Muhammad Umair, Nelson, Maggie, Bivona, Cory R, Godwin, Andrew, Sharma, Priyanka, Martin, Grace, Li, Kevin, Streeter, Natalie, Zhang, Jun, Abdelhakim, Haitham, Hoffmann, Marc, Liu, Ben, Zheng, Cucong, Mitchell, Laura, Pessetto, Ziyan, Pathak, Harsh, Abhyankar, Sunil, Khan, Qamar, and McGuirk, Joseph P.

Published
2022
Full Text
View/download PDF

38. Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CDpro

Author

Wimmer Eckard, Rombaut Bart, Cameron Craig E, Pathak Harsh B, Franco David, and Paul Aniko V

Subjects
Poliovirus, RNA replication, virus maturation, HeLa cell-free translation-RNA replication system, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Poliovirus protein 3CDpro possesses both proteinase and RNA binding activities, which are located in the 3Cpro domain of the protein. The RNA polymerase (3Dpol) domain of 3CDpro modulates these activities of the protein. We have recently shown that the level of 3CDpro in HeLa cell-free in vitro translation-RNA replication reactions is suboptimal for efficient virus production. However, the addition of either 3CDpro mRNA or of purified 3CDpro protein to in vitro reactions, programmed with viral RNA, results in a 100-fold increase in virus yield. Mutational analyses of 3CDpro indicated that RNA binding by the 3Cpro domain and the integrity of interface I in the 3Dpol domain of the protein are both required for function. The aim of these studies was to determine the exact step or steps at which 3CDpro enhances virus yield and to determine the mechanism by which this occurs. Our results suggest that the addition of extra 3CDpro to in vitro translation RNA-replication reactions results in a mild enhancement of both minus and plus strand RNA synthesis. By examining the viral particles formed in the in vitro reactions on sucrose gradients we determined that 3CDpro has only a slight stimulating effect on the synthesis of capsid precursors but it strikingly enhances the maturation of virus particles. Both the stimulation of RNA synthesis and the maturation of the virus particles are dependent on the presence of an intact RNA binding site within the 3Cpro domain of 3CDpro. In addition, the integrity of interface I in the 3Dpol domain of 3CDpro is required for efficient production of mature virus. Surprisingly, plus strand RNA synthesis and virus production in in vitro reactions, programmed with full-length transcript RNA, are not enhanced by the addition of extra 3CDpro. Our results indicate that the stimulation of RNA synthesis and virus maturation by 3CDpro in vitro is dependent on the presence of a VPg-linked RNA template.

Published
2005
Full Text
View/download PDF

41. PTN Signaling: Components and Mechanistic Insights in Human Ovarian Cancer

Author

Sethi, Geetika, Kwon, Youngjoo, Burkhalter, Rebecca J, Pathak, Harsh B., Madan, Rashna, McHugh, Sarah, Atay, Safinur, Murthy, Smruthi, Tawfik, Ossama W., and Godwin, Andrew K.

Subjects
Adult, Aged, 80 and over, Ovarian Neoplasms, endocrine system diseases, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Apoptosis, Carcinoma, Ovarian Epithelial, Middle Aged, female genital diseases and pregnancy complications, Article, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cytokines, Humans, Female, Gene Silencing, Neoplasms, Glandular and Epithelial, Mitogen-Activated Protein Kinases, RNA, Small Interfering, Carrier Proteins, Aged, Signal Transduction
Abstract

Molecular vulnerabilities represent promising candidates for the development of targeted therapies that hold the promise to overcome the challenges encountered with non-targeted chemotherapy for the treatment of ovarian cancer. Through a synthetic lethality screen, we previously identified pleiotrophin (PTN) as a molecular vulnerability in ovarian cancer and showed that siRNA-mediated PTN knockdown induced apoptotic cell death in epithelial ovarian cancer (EOC) cells. Although, it is well known that PTN elicits its pro-tumorigenic effects through its receptor, protein tyrosine phosphatase receptor Z1 (PTPRZ1), little is known about the potential importance of this pathway in the pathogenesis of ovarian cancer. In this study, we show that PTN is expressed, produced, and secreted in a panel of EOC cell lines. PTN levels in serous ovarian tumor tissues are on average 3.5-fold higher relative to normal tissue and PTN is detectable in serum samples of patients with EOC. PTPRZ1 is also expressed and produced by EOC cells and is found to be up-regulated in serous ovarian tumor tissue relative to normal ovarian surface epithelial tissue (P0.05). Gene silencing of PTPRZ1 in EOC cell lines using siRNA-mediated knockdown shows that PTPRZ1 is essential for viability and results in significant apoptosis with no effect on the cell cycle phase distribution. In order to determine how PTN mediates survival, we silenced the gene using siRNA mediated knockdown and performed expression profiling of 36 survival-related genes. Through computational mapping of the differentially expressed genes, members of the MAPK (mitogen-activated protein kinase) family were found to be likely effectors of PTN signaling in EOC cells. Our results provide the first experimental evidence that PTN and its signaling components may be of significance in the pathogenesis of epithelial ovarian cancer and provide a rationale for clinical evaluation of MAPK inhibitors in PTN and/or PTPRZ1 expressing ovarian tumors.

Published
2014

43. A Synthetic Lethality Screen Using a Focused siRNA Library to Identify Sensitizers to Dasatinib Therapy for the Treatment of Epithelial Ovarian Cancer.

Author

Pathak, Harsh B, Zhou, Yan, Sethi, Geetika, Hirst, Jeff, Schilder, Russell J, Golemis, Erica A, Godwin, Andrew K, Pathak, Harsh B, Zhou, Yan, Sethi, Geetika, Hirst, Jeff, Schilder, Russell J, Golemis, Erica A, and Godwin, Andrew K

Abstract

Molecular targeted therapies have been the focus of recent clinical trials for the treatment of patients with recurrent epithelial ovarian cancer (EOC). The majority have not fared well as monotherapies for improving survival of these patients. Poor bioavailability, lack of predictive biomarkers, and the presence of multiple survival pathways can all diminish the success of a targeted agent. Dasatinib is a tyrosine kinase inhibitor of the Src-family kinases (SFK) and in preclinical studies shown to have substantial activity in EOC. However, when evaluated in a phase 2 clinical trial for patients with recurrent or persistent EOC, it was found to have minimal activity. We hypothesized that synthetic lethality screens performed using a cogently designed siRNA library would identify second-site molecular targets that could synergize with SFK inhibition and improve dasatinib efficacy. Using a systematic approach, we performed primary siRNA screening using a library focused on 638 genes corresponding to a network centered on EGFR, HER2, and the SFK-scaffolding proteins BCAR1, NEDD9, and EFS to screen EOC cells in combination with dasatinib. We followed up with validation studies including deconvolution screening, quantitative PCR to confirm effective gene silencing, correlation of gene expression with dasatinib sensitivity, and assessment of the clinical relevance of hits using TCGA ovarian cancer data. A refined list of five candidates (CSNK2A1, DAG1, GRB2, PRKCE, and VAV1) was identified as showing the greatest potential for improving sensitivity to dasatinib in EOC. Of these, CSNK2A1, which codes for the catalytic alpha subunit of protein kinase CK2, was selected for additional evaluation. Synergistic activity of the clinically relevant inhibitor of CK2, CX-4945, with dasatinib in reducing cell proliferation and increasing apoptosis was observed across multiple EOC cell lines. This overall approach to improving drug efficacy can be applied to other targeted agents that

Published
2015

45. A perspective on joint venture: an international business expansion strategy and legal implications with specific reference to India.

Author

PATHAK, Harsh

Subjects
INTERNATIONAL business enterprises, JOINT ventures, MARKETING strategy, APPELLATE courts
Abstract

Collaboration between firms is not a new concept, but the new thing that can be seen is that the collaborations have increased significantly during the past couple of decades, along with the increasing international competition. Moreover, the nature of collaboration has changed, shifting from peripheral interests to the very core functions of the corporation, and from equity to non-equity forms of collaboration. This paper essentially focuses on the legal framework governing the various aspects of a Joint Venture in India in brief, the methods of Joint Ventures, as well as RBI regulations on the topic. The research methodology adopted is largely analytical and descriptive. Reliance has been placed largely on various sources like articles and online articles. [ABSTRACT FROM AUTHOR]

Published
2018

46. Common Breast Cancer Susceptibility Loci Are Associated with Triple-Negative Breast Cancer

Author

Stevens, Kristen N. Vachon, Celine M. Lee, Adam M. Slager, Susan Lesnick, Timothy Olswold, Curtis Fasching, Peter A. and Miron, Penelope Eccles, Diana Carpenter, Jane E. Godwin, Andrew K. Ambrosone, Christine Winqvist, Robert Brauch, Hiltrud Schmidt, Marjanka K. Cox, Angela Cross, Simon S. and Sawyer, Elinor Hartmann, Arndt Beckmann, Matthias W. and Schulz-Wendtland, Ruediger Ekici, Arif B. Tapper, William J. and Gerty, Susan M. Durcan, Lorraine Graham, Nikki Hein, Rebecca and Nickels, Stephan Flesch-Janys, Dieter Heinz, Judith and Sinn, Hans-Peter Konstantopoulou, Irene Fostira, Florentia and Pectasides, Dimitrios Dimopoulos, Athanasios M. Fountzilas, George Clarke, Christine L. Balleine, Rosemary Olson, Janet E. Fredericksen, Zachary Diasio, Robert B. Pathak, Harsh and Ross, Eric Weaver, JoEllen Ruediger, Thomas Forsti, Asta and Duennebier, Thomas Ademuyiwa, Foluso Kulkarni, Swati and Pylkaes, Katri Jukkola-Vuorinen, Arja Ko, Yon-Dschun Van Limbergen, Erik Janssen, Hilde Peto, Julian Fletcher, Olivia and Giles, Graham G. Baglietto, Laura Verhoef, Senno and Tomlinson, Ian Kosma, Veli-Matti Beesley, Jonathan Greco, Dario Blomqvist, Carl Irwanto, Astrid Liu, Jianjun and Blows, Fiona M. Dawson, Sarah-Jane Margolin, Sara Mannermaa, Arto Martin, Nicholas G. Montgomery, Grant W. Lambrechts, Diether Silva, Isabel dos Santos Severi, Gianluca Hamann, Ute Pharoah, Paul Easton, Douglas F. Chang-Claude, Jenny and Yannoukakos, Drakoulis Nevanlinna, Heli Wang, Xianshu Couch, Fergus J. GENICA Consortium

Subjects
skin and connective tissue diseases
Abstract

Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240-9. (C)2011 AACR.

Published
2011

47. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer

Author

Haiman, Christopher A. Chen, Gary K. Vachon, Celine M. and Canzian, Federico Dunning, Alison Millikan, Robert C. Wang, Xianshu Ademuyiwa, Foluso Ahmed, Shahana Ambrosone, Christine B. Baglietto, Laura Balleine, Rosemary Bandera, Elisa V. Beckmann, Matthias W. Berg, Christine D. Bernstein, Leslie Blomqvist, Carl Blot, William J. Brauch, Hiltrud and Buring, Julie E. Carey, Lisa A. Carpenter, Jane E. and Chang-Claude, Jenny Chanock, Stephen J. Chasman, Daniel I. and Clarke, Christine L. Cox, Angela Cross, Simon S. Deming, Sandra L. Diasio, Robert B. Dimopoulos, Athanasios M. and Driver, W. Ryan Duennebier, Thomas Durcan, Lorraine Eccles, Diana Edlund, Christopher K. Ekici, Arif B. Fasching, Peter A. Feigelson, Heather S. Flesch-Janys, Dieter Fostira, Florentia Foersti, Asta Fountzilas, George Gerty, Susan M. and Giles, Graham G. Godwin, Andrew K. Goodfellow, Paul and Graham, Nikki Greco, Dario Hamann, Ute Hankinson, Susan E. and Hartmann, Arndt Hein, Rebecca Heinz, Judith Holbrook, Andrea Hoover, Robert N. Hu, Jennifer J. Hunter, David J. and Ingles, Sue A. Irwanto, Astrid Ivanovich, Jennifer John, Esther M. Johnson, Nicola Jukkola-Vuorinen, Arja Kaaks, Rudolf Ko, Yon-Dschun Kolonel, Laurence N. Konstantopoulou, Irene Kosma, Veli-Matti Kulkarni, Swati Lambrechts, Diether and Lee, Adam M. Le Marchand, Loic Lesnick, Timothy Liu, Jianjun Lindstrom, Sara Mannermaa, Arto Margolin, Sara and Martin, Nicholas G. Miron, Penelope Montgomery, Grant W. and Nevanlinna, Heli Nickels, Stephan Nyante, Sarah Olswold, Curtis Palmer, Julie Pathak, Harsh Pectasides, Dimitrios and Perou, Charles M. Peto, Julian Pharoah, Paul D. P. Pooler, Loreall C. Press, Michael F. Pylkas, Katri Rebbeck, Timothy R. Rodriguez-Gil, Jorge L. Rosenberg, Lynn Ross, Eric and Ruediger, Thomas Silva, Isabel dos Santos Sawyer, Elinor and Schmidt, Marjanka K. Schulz-Wendtland, Ruediger Schumacher, Fredrick Severi, Gianluca Sheng, Xin Signorello, Lisa B. and Sinn, Hans-Peter Stevens, Kristen N. Southey, Melissa C. and Tapper, William J. Tomlinson, Ian Hogervorst, Frans B. L. and Wauters, Els Weaver, JoEllen Wildiers, Hans Winqvist, Robert and Van Den Berg, David Wan, Peggy Xia, Lucy Y. Yannoukakos, Drakoulis Zheng, Wei Ziegler, Regina G. Siddiq, Afshan and Slager, Susan L. Stram, Daniel O. Easton, Douglas Kraft, Peter Henderson, Brian E. Couch, Fergus J. Gene Environm Interaction Breast C

Abstract

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (

Published
2011

48. 19p13.1 is a triple negative-specific breast cancer susceptibility locus

Author

Stevens, Kristen N, Fredericksen, Zachary, Vachon, Celine M, Wang, Xianshu, Margolin, Sara, Lindblom, Annika, Nevanlinna, Heli, Greco, Dario, Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Vrieling, Alina, Flesch-Janys, Dieter, Sinn, Hans-Peter, Wang-Gohrke, Shan, Nickels, Stefan, Brauch, Hiltrud, Ko, Yon-Dschun, Fischer, Hans-Peter, Network, The Genica, Schmutzler, Rita K, Meindl, Alfons, Bartram, Claus R, Schott, Sarah, Engel, Christoph, Godwin, Andrew K, Weaver, Joellen, Pathak, Harsh B, Sharma, Priyanka, Brenner, Hermann, Muller, Heiko, Arndt, Volker, Stegmaier, Christa, Miron, Penelope, Yannoukakos, Drakoulis, Stavropoulou, Alexandra, Fountzilas, George, Gogas, Helen J, Swann, Ruth, Dwek, Miriam, Perkins, Katherine Anne, Milne, Roger L, Benítez, Javier, Zamora, M Pilar, Ignacio Arias Pérez, José, Bojesen, Stig E, Nielsen, Sune F, Nordestgaard, Borge G, Flyger, Henrik, Guénel, Pascal, Truong, Thérèse, Menegaux, Florence, Cordina-Duverger, Emilie, Burwinkel, Barbara, Marmé, Frederick, Schneeweiss, Andreas, Sohn, Christof, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael J, Peto, Julian, Johnson, Nichola, Fletcher, Olivia, Dos Santos Silva, Isabel, Fasching, Peter A, Beckmann, Matthias W, Hartmann, Arndt, Ekici, Arif B, Lophatananon, Artitaya, Muir, Kenneth, Puttawibul, Puttisak, Wiangnon, Surapon, Schmidt, Marjanka K, Broeks, Annegien, Braaf, Linde M, Rosenberg, Efraim H, Hopper, John L, Apicella, Carmel, Park, Daniel J, Southey, Melissa C, Swerdlow, Anthony J, Ashworth, Alan, Orr, Nick, Schoemaker, Minouk J, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Clarke Dur, Christina, Shen, Chen-Yang, Yu, Jyh-Cherng, Hsu, Huan-Ming, Hsiung, Chia-Ni, Hamann, Ute, Dünnebier, Thomas, Rüdiger, Thomas, Ulrich Ulmer, Hans, Pharoah, Paul D P, Dunning, Alison M, Humphreys, Manjeet K, Wang, Qin, Cox, Angela, Cross, Simon S, Reed, Malcolm W R, Hall, Per, Czene, Kamila, Ambrosone, Christine B, Ademuyiwa, Foluso, Hwang, Helena, Eccles, Diana M, Garcia-Closas, Montserrat, Figueroa, Jonine D, Sherman, Mark E, Lissowska, Jolanta, Devilee, Peter, Seynaeve, Caroline, Tollenaar, R A E M, Hooning, Maartje J, Andrulis, Irene L, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, John, Esther M, Miron, Alexander, Grenaker Alnaes, Grethe, Kristensen, Vessela, Borresen-Dale, Anne-Lise, Giles, Graham G, Baglietto, Laura, McLean, Catriona A, Severi, Gianluca, Kosel, Matthew L, Pankratz, V Shane, Slager, Susan, Olson, Janet E, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Barile, Monica, Lambrechts, Diether, Hatse, Sigrid, Dieudonne, Anne-Sophie, Christiaens, Marie-Rose, Chenevix-Trench, Georgia, Investigators, Kconfab, Group, Aocs, Beesley, Jonathan, Chen, Xiaoqing, Mannermaa, Arto, Kosma, Veli-Matti, Hartikainen, Jaana M, Soini, Ylermi, Easton, Douglas F, Couch, Fergus J, Stevens, Kristen N, Fredericksen, Zachary, Vachon, Celine M, Wang, Xianshu, Margolin, Sara, Lindblom, Annika, Nevanlinna, Heli, Greco, Dario, Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Vrieling, Alina, Flesch-Janys, Dieter, Sinn, Hans-Peter, Wang-Gohrke, Shan, Nickels, Stefan, Brauch, Hiltrud, Ko, Yon-Dschun, Fischer, Hans-Peter, Network, The Genica, Schmutzler, Rita K, Meindl, Alfons, Bartram, Claus R, Schott, Sarah, Engel, Christoph, Godwin, Andrew K, Weaver, Joellen, Pathak, Harsh B, Sharma, Priyanka, Brenner, Hermann, Muller, Heiko, Arndt, Volker, Stegmaier, Christa, Miron, Penelope, Yannoukakos, Drakoulis, Stavropoulou, Alexandra, Fountzilas, George, Gogas, Helen J, Swann, Ruth, Dwek, Miriam, Perkins, Katherine Anne, Milne, Roger L, Benítez, Javier, Zamora, M Pilar, Ignacio Arias Pérez, José, Bojesen, Stig E, Nielsen, Sune F, Nordestgaard, Borge G, Flyger, Henrik, Guénel, Pascal, Truong, Thérèse, Menegaux, Florence, Cordina-Duverger, Emilie, Burwinkel, Barbara, Marmé, Frederick, Schneeweiss, Andreas, Sohn, Christof, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael J, Peto, Julian, Johnson, Nichola, Fletcher, Olivia, Dos Santos Silva, Isabel, Fasching, Peter A, Beckmann, Matthias W, Hartmann, Arndt, Ekici, Arif B, Lophatananon, Artitaya, Muir, Kenneth, Puttawibul, Puttisak, Wiangnon, Surapon, Schmidt, Marjanka K, Broeks, Annegien, Braaf, Linde M, Rosenberg, Efraim H, Hopper, John L, Apicella, Carmel, Park, Daniel J, Southey, Melissa C, Swerdlow, Anthony J, Ashworth, Alan, Orr, Nick, Schoemaker, Minouk J, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Clarke Dur, Christina, Shen, Chen-Yang, Yu, Jyh-Cherng, Hsu, Huan-Ming, Hsiung, Chia-Ni, Hamann, Ute, Dünnebier, Thomas, Rüdiger, Thomas, Ulrich Ulmer, Hans, Pharoah, Paul D P, Dunning, Alison M, Humphreys, Manjeet K, Wang, Qin, Cox, Angela, Cross, Simon S, Reed, Malcolm W R, Hall, Per, Czene, Kamila, Ambrosone, Christine B, Ademuyiwa, Foluso, Hwang, Helena, Eccles, Diana M, Garcia-Closas, Montserrat, Figueroa, Jonine D, Sherman, Mark E, Lissowska, Jolanta, Devilee, Peter, Seynaeve, Caroline, Tollenaar, R A E M, Hooning, Maartje J, Andrulis, Irene L, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, John, Esther M, Miron, Alexander, Grenaker Alnaes, Grethe, Kristensen, Vessela, Borresen-Dale, Anne-Lise, Giles, Graham G, Baglietto, Laura, McLean, Catriona A, Severi, Gianluca, Kosel, Matthew L, Pankratz, V Shane, Slager, Susan, Olson, Janet E, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Barile, Monica, Lambrechts, Diether, Hatse, Sigrid, Dieudonne, Anne-Sophie, Christiaens, Marie-Rose, Chenevix-Trench, Georgia, Investigators, Kconfab, Group, Aocs, Beesley, Jonathan, Chen, Xiaoqing, Mannermaa, Arto, Kosma, Veli-Matti, Hartikainen, Jaana M, Soini, Ylermi, Easton, Douglas F, and Couch, Fergus J

Abstract

The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.

Published
2012
Full Text
View/download PDF

49. A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

Author

Ding, Yuan C, McGuffog, Lesley, Healey, Sue, Friedman, Eitan, Laitman, Yael, Paluch-Shimon, Shani, Kaufman, Bella, Liljegren, Annelie, Lindblom, Annika, Olsson, Hakan, Kristoffersson, Ulf, Stenmark Askmalm, Marie, Melin, Beatrice, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Huzarski, Tomasz, Cybulski, Cezary, Byrski, Tomasz, Osorio, Ana, Ramony Cajal, Teresa, Stavropoulou, Alexandra V, Benitez, Javier, Hamann, Ute, Rookus, Matti, Aalfs, Cora M, de Lange, Judith L, Meijers-Heijboer, Hanne E J, Oosterwijk, Jan C, van Asperen, Christi J, Gomez Garcia, Encarna B, Hoogerbrugge, Nicoline, Jager, Agnes, van der Luijt, Rob B, Easton, Douglas F, Peock, Susan, Frost, Debra, Ellis, Steve D, Platte, Radka, Fineberg, Elena, Evans, D Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Brewer, Carole, Tischkowitz, Marc, Godwin, Andrew K, Pathak, Harsh, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M, Mazoyer, Sylvie, Barjhoux, Laure, Leone, Melanie, Gauthier-Villars, Marion, Caux-Moncoutier, Virginie, de Pauw, Antoine, Hardouin, Agnes, Berthet, Pascaline, Dreyfus, Helene, Fert Ferrer, Sandra, Collonge-Rame, Marie-Agnes, Sokolowska, Johanna, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy, John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng Maria, Gschwantler-Kaulich, Daphne, Fink-Retter, Anneliese, Hansen, Thomas V O, Ejlertsen, Bent, Johannsson, Oskar T, Offit, Kenneth, Sarrel, Kara, Gaudet, Mia M, Vijai, Joseph, Robson, Mark, Piedmonte, Marion R, Andrews, Lesley, Cohn, David, DeMars, Leslie R, DiSilvestro, Paul, Rodriguez, Gustavo, Ewart Toland, Amanda, Montagna, Marco, Agata, Simona, Imyanitov, Evgeny, Isaacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Ramus, Susan J, Sucheston, Lara, Karlan, Beth Y, Gross, Jenny, Ganz, Patricia A, Beattie, Mary S, Schmutzler, Rita K, Wappenschmidt, Barbara, Meindl, Alfons, Arnold, Norbert, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Nevanlinna, Heli, Aittomaki, Kristiina, Spurdle, Amanda B, Beesley, Jonathan, Chen, Xiaoqing, Tomlinson, Gail E, Weitzel, Jeffrey, Garber, Judy E, Olopade, Olufunmilayo I, Rubinstein, Wendy S, Tung, Nadine, Blum, Joanne L, Narod, Steven A, Brummel, Sean, Gillen, Daniel L, Lindor, Noralane, Fredericksen, Zachary, Pankratz, Vernon S, Couch, Fergus J, Radice, Paolo, Peterlongo, Paolo, Greene, Mark H, Loud, Jennifer T, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Gerdes, Anne-Marie, Birk Jensen, Uffe, Skytte, Anne-Bine, Caligo, Maria A, Lee, Andrew, Chenevix-Trench, Georgia, Antoniou, Antonis C, Neuhausen, Susan L, Ding, Yuan C, McGuffog, Lesley, Healey, Sue, Friedman, Eitan, Laitman, Yael, Paluch-Shimon, Shani, Kaufman, Bella, Liljegren, Annelie, Lindblom, Annika, Olsson, Hakan, Kristoffersson, Ulf, Stenmark Askmalm, Marie, Melin, Beatrice, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Gronwald, Jacek, Huzarski, Tomasz, Cybulski, Cezary, Byrski, Tomasz, Osorio, Ana, Ramony Cajal, Teresa, Stavropoulou, Alexandra V, Benitez, Javier, Hamann, Ute, Rookus, Matti, Aalfs, Cora M, de Lange, Judith L, Meijers-Heijboer, Hanne E J, Oosterwijk, Jan C, van Asperen, Christi J, Gomez Garcia, Encarna B, Hoogerbrugge, Nicoline, Jager, Agnes, van der Luijt, Rob B, Easton, Douglas F, Peock, Susan, Frost, Debra, Ellis, Steve D, Platte, Radka, Fineberg, Elena, Evans, D Gareth, Lalloo, Fiona, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Brewer, Carole, Tischkowitz, Marc, Godwin, Andrew K, Pathak, Harsh, Stoppa-Lyonnet, Dominique, Sinilnikova, Olga M, Mazoyer, Sylvie, Barjhoux, Laure, Leone, Melanie, Gauthier-Villars, Marion, Caux-Moncoutier, Virginie, de Pauw, Antoine, Hardouin, Agnes, Berthet, Pascaline, Dreyfus, Helene, Fert Ferrer, Sandra, Collonge-Rame, Marie-Agnes, Sokolowska, Johanna, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy, John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng Maria, Gschwantler-Kaulich, Daphne, Fink-Retter, Anneliese, Hansen, Thomas V O, Ejlertsen, Bent, Johannsson, Oskar T, Offit, Kenneth, Sarrel, Kara, Gaudet, Mia M, Vijai, Joseph, Robson, Mark, Piedmonte, Marion R, Andrews, Lesley, Cohn, David, DeMars, Leslie R, DiSilvestro, Paul, Rodriguez, Gustavo, Ewart Toland, Amanda, Montagna, Marco, Agata, Simona, Imyanitov, Evgeny, Isaacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Ignacio, Ramus, Susan J, Sucheston, Lara, Karlan, Beth Y, Gross, Jenny, Ganz, Patricia A, Beattie, Mary S, Schmutzler, Rita K, Wappenschmidt, Barbara, Meindl, Alfons, Arnold, Norbert, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Nevanlinna, Heli, Aittomaki, Kristiina, Spurdle, Amanda B, Beesley, Jonathan, Chen, Xiaoqing, Tomlinson, Gail E, Weitzel, Jeffrey, Garber, Judy E, Olopade, Olufunmilayo I, Rubinstein, Wendy S, Tung, Nadine, Blum, Joanne L, Narod, Steven A, Brummel, Sean, Gillen, Daniel L, Lindor, Noralane, Fredericksen, Zachary, Pankratz, Vernon S, Couch, Fergus J, Radice, Paolo, Peterlongo, Paolo, Greene, Mark H, Loud, Jennifer T, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Gerdes, Anne-Marie, Birk Jensen, Uffe, Skytte, Anne-Bine, Caligo, Maria A, Lee, Andrew, Chenevix-Trench, Georgia, Antoniou, Antonis C, and Neuhausen, Susan L

Abstract

Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. less thanbrgreater than less thanbrgreater thanMethods: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. less thanbrgreater than less thanbrgreater thanResults: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P-difference, 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03). less thanbrgreater than less thanbrgreater thanConclusion: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers. less thanbrgreater than less thanbrgreater thanImpact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers., Funding Agencies|NIH|R01CA74415P30CA033752|Israel cancer association||Mutua Madrilena Foundation||Red de Investigacion en Cancer|RD06/0020/1160|Spanish Ministry of Science and Innovation|FIS P1081120SAF2010-20493|Cancer Research UK|C1287/A10118C1287/A11990C5047/A8385|NIHR||NEYE Foundation||Clinical Genetics Branch, DCEG National Cancer Institute (NCI)||Community Oncology and Prevention Trials Program-COPTRG National Cancer Institute (NCI)||Russian Foundation for Basic Research|10-04-9211010-04-9260111-04-00227|Federal Agency for Science and Innovations|02.740.11.0780|Royal Society|JP090615|Research Council of Lithuania|LIG-19/2010|Institut Catala dOncologia (ICO)||Asociacion Espanola Contra el Cancer, Spanish Health Research Fund||Carlos III Health Institute||Catalan Health Institute||Autonomous Government of Catalonia|ISCIIIRETIC RD06/0020/1051PI10/01422PI10/314882009SGR290|American Cancer Society|120950-SIOP-06-258-06-COUN|German Cancer Aid|DKH 109076|Helsinki University Central Hospital||Academy of Finland|132473|Finnish Cancer Society||Sigrid Juselius Foundation||Canadian Institutes of Health Research||Canadian Breast Cancer Research Alliance|019511|NCI, under RFA|CA-06-503|Cancer Care Ontario|U01 CA69467|Cancer Prevention Institute of California|U01 CA69417|Columbia University|U01 CA69398|Fox Chase Cancer Center|U01 CA69631|Huntsman Cancer Institute|U01 CA69446|University of Melbourne|U01 CA69638|National Health and Medical Research Council of Australia||New South Wales Cancer Council||Victorian Health Promotion Foundation (Australia)||Victorian Breast Cancer Research Consortium||NITA|P01 CA16094R01 CA22435|National Institutes of Health|P30 CA13696P30 ES009089UL1 RR025764R01278978|National Center for Research Resources||National Center for Advancing Translational Sciences||NCI|P30 CA042014|NHMRC|145684288704454508|US NCI at the NIH|NO2-CP-11019-50N02-CP-65504|Westat, Inc.||Breast cancer Research Foundation||Komen Foundation for the Cure||Dutch Cancer Society

Published
2012
Full Text
View/download PDF

50. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Author

Ramus, Susan J, Antoniou, Antonis C, Kuchenbaecker, Karoline B, Soucy, Penny, Beesley, Jonathan, Chen, Xiaoqing, McGuffog, Lesley, Sinilnikova, Olga M, Healey, Sue, Barrowdale, Daniel, Lee, Andrew, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Liljegren, Annelie, Lindblom, Annika, Olsson, Håkan, Kristoffersson, Ulf, Stenmark-Askmalm, Marie, Melin, Beatrice, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Tejada, Maria-Isabel, Hamann, Ute, Rookus, Matti, van Leeuwen, Flora E, Aalfs, Cora M, Meijers-Heijboer, Hanne E J, van Asperen, Christi J, van Roozendaal, K E P, Hoogerbrugge, Nicoline, Collée, J Margriet, Kriege, Mieke, van der Luijt, Rob B, Peock, Susan, Frost, Debra, Ellis, Steve D, Platte, Radka, Fineberg, Elena, Evans, D Gareth, Lalloo, Fiona, Jacobs, Chris, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Paterson, Joan, Douglas, Fiona, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J, Walker, Lisa, Porteous, Mary E, Kennedy, M John, Pathak, Harsh, Godwin, Andrew K, Stoppa-Lyonnet, Dominique, Caux-Moncoutier, Virginie, de Pauw, Antoine, Gauthier-Villars, Marion, Mazoyer, Sylvie, Léoné, Mélanie, Calender, Alain, Lasset, Christine, Bonadona, Valérie, Hardouin, Agnès, Berthet, Pascaline, Bignon, Yves-Jean, Uhrhammer, Nancy, Faivre, Laurence, Loustalot, Catherine, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy K, John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng, Pfeiler, Georg, Fink-Retter, Anneliese, Hansen, Thomas v O, Ejlertsen, Bent, Johannsson, Oskar Th, Offit, Kenneth, Kirchhoff, Tomas, Gaudet, Mia M, Vijai, Joseph, Robson, Mark, Piedmonte, Marion, Phillips, Kelly-Anne, Van Le, Linda, Hoffman, James S, Ewart Toland, Amanda, Montagna, Marco, Tognazzo, Silvia, Imyanitov, Evgeny, Issacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Iganacio, Tornero, Eva, Navarro, Matilde, Moysich, Kirsten B, Karlan, Beth Y, Gross, Jenny, Olah, Edith, Vaszko, Tibor, Teo, Soo-Hwang, Ganz, Patricia A, Beattie, Mary S, Dorfling, Cecelia M, van Rensburg, Elizabeth J, Diez, Orland, Kwong, Ava, Schmutzler, Rita K, Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Heidemann, Simone, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Fiebig, Britta, Schäfer, Dieter, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Plante, Marie, Spurdle, Amanda B, Neuhausen, Susan L, Ding, Yuan Chun, Wang, Xianshu, Lindor, Noralane, Fredericksen, Zachary, Pankratz, V Shane, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Bonanni, Bernardo, Bernard, Loris, Dolcetti, Riccardo, Papi, Laura, Ottini, Laura, Radice, Paolo, Greene, Mark H, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Ozcelik, Hilmi, Pharoah, Paul D P, Gayther, Simon A, Simard, Jacques, Easton, Douglas F, Couch, Fergus J, Chenevix-Trench, Georgia, Ramus, Susan J, Antoniou, Antonis C, Kuchenbaecker, Karoline B, Soucy, Penny, Beesley, Jonathan, Chen, Xiaoqing, McGuffog, Lesley, Sinilnikova, Olga M, Healey, Sue, Barrowdale, Daniel, Lee, Andrew, Thomassen, Mads, Gerdes, Anne-Marie, Kruse, Torben A, Jensen, Uffe Birk, Skytte, Anne-Bine, Caligo, Maria A, Liljegren, Annelie, Lindblom, Annika, Olsson, Håkan, Kristoffersson, Ulf, Stenmark-Askmalm, Marie, Melin, Beatrice, Domchek, Susan M, Nathanson, Katherine L, Rebbeck, Timothy R, Jakubowska, Anna, Lubinski, Jan, Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Gronwald, Jacek, Huzarski, Tomasz, Byrski, Tomasz, Cybulski, Cezary, Toloczko-Grabarek, Aleksandra, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Tejada, Maria-Isabel, Hamann, Ute, Rookus, Matti, van Leeuwen, Flora E, Aalfs, Cora M, Meijers-Heijboer, Hanne E J, van Asperen, Christi J, van Roozendaal, K E P, Hoogerbrugge, Nicoline, Collée, J Margriet, Kriege, Mieke, van der Luijt, Rob B, Peock, Susan, Frost, Debra, Ellis, Steve D, Platte, Radka, Fineberg, Elena, Evans, D Gareth, Lalloo, Fiona, Jacobs, Chris, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Eccles, Diana, Cole, Trevor, Cook, Jackie, Paterson, Joan, Douglas, Fiona, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J, Walker, Lisa, Porteous, Mary E, Kennedy, M John, Pathak, Harsh, Godwin, Andrew K, Stoppa-Lyonnet, Dominique, Caux-Moncoutier, Virginie, de Pauw, Antoine, Gauthier-Villars, Marion, Mazoyer, Sylvie, Léoné, Mélanie, Calender, Alain, Lasset, Christine, Bonadona, Valérie, Hardouin, Agnès, Berthet, Pascaline, Bignon, Yves-Jean, Uhrhammer, Nancy, Faivre, Laurence, Loustalot, Catherine, Buys, Saundra, Daly, Mary, Miron, Alex, Terry, Mary Beth, Chung, Wendy K, John, Esther M, Southey, Melissa, Goldgar, David, Singer, Christian F, Tea, Muy-Kheng, Pfeiler, Georg, Fink-Retter, Anneliese, Hansen, Thomas v O, Ejlertsen, Bent, Johannsson, Oskar Th, Offit, Kenneth, Kirchhoff, Tomas, Gaudet, Mia M, Vijai, Joseph, Robson, Mark, Piedmonte, Marion, Phillips, Kelly-Anne, Van Le, Linda, Hoffman, James S, Ewart Toland, Amanda, Montagna, Marco, Tognazzo, Silvia, Imyanitov, Evgeny, Issacs, Claudine, Janavicius, Ramunas, Lazaro, Conxi, Blanco, Iganacio, Tornero, Eva, Navarro, Matilde, Moysich, Kirsten B, Karlan, Beth Y, Gross, Jenny, Olah, Edith, Vaszko, Tibor, Teo, Soo-Hwang, Ganz, Patricia A, Beattie, Mary S, Dorfling, Cecelia M, van Rensburg, Elizabeth J, Diez, Orland, Kwong, Ava, Schmutzler, Rita K, Wappenschmidt, Barbara, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Heidemann, Simone, Niederacher, Dieter, Preisler-Adams, Sabine, Gadzicki, Dorotehea, Varon-Mateeva, Raymonda, Deissler, Helmut, Gehrig, Andrea, Sutter, Christian, Kast, Karin, Fiebig, Britta, Schäfer, Dieter, Caldes, Trinidad, de la Hoya, Miguel, Nevanlinna, Heli, Aittomäki, Kristiina, Plante, Marie, Spurdle, Amanda B, Neuhausen, Susan L, Ding, Yuan Chun, Wang, Xianshu, Lindor, Noralane, Fredericksen, Zachary, Pankratz, V Shane, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Bonanni, Bernardo, Bernard, Loris, Dolcetti, Riccardo, Papi, Laura, Ottini, Laura, Radice, Paolo, Greene, Mark H, Mai, Phuong L, Andrulis, Irene L, Glendon, Gord, Ozcelik, Hilmi, Pharoah, Paul D P, Gayther, Simon A, Simard, Jacques, Easton, Douglas F, Couch, Fergus J, and Chenevix-Trench, Georgia

Abstract

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results