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104 results on '"Georgia, Chenevix-Trench"'

1. Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease

Author: Dhanya Ramachandran, Jonathan P. Tyrer, Stefan Kommoss, Anna DeFazio, Marjorie J. Riggan, AOCS Group, Penelope M. Webb, Peter A. Fasching, Diether Lambrechts, María J. García, Cristina Rodríguez-Antona, Marc T. Goodman, Francesmary Modugno, Kirsten B. Moysich, Beth Y. Karlan, Jenny Lester, Susanne K. Kjaer, Allan Jensen, Estrid Høgdall, Ellen L. Goode, William A. Cliby, Amanika Kumar, Chen Wang, Julie M. Cunningham, Stacey J. Winham, Alvaro N. Monteiro, Joellen M. Schildkraut, Daniel W. Cramer, Kathryn L. Terry, Linda Titus, Line Bjorge, Liv Cecilie Vestrheim Thomsen, OPAL Study Group, Tanja Pejovic, Claus K. Høgdall, Iain A. McNeish, Taymaa May, David G. Huntsman, Jacobus Pfisterer, Ulrich Canzler, Tjoung-Won Park-Simon, Willibald Schröder, Antje Belau, Lars Hanker, Philipp Harter, Jalid Sehouli, Rainer Kimmig, Nikolaus de Gregorio, Barbara Schmalfeldt, Klaus Baumann, Felix Hilpert, Alexander Burges, Boris Winterhoff, Peter Schürmann, Lisa-Marie Speith, Peter Hillemanns, Andrew Berchuck, Sharon E. Johnatty, Susan J. Ramus, Georgia Chenevix-Trench, Paul D. P. Pharoah, Thilo Dörk, and Florian Heitz
Subjects: Medicine, Genetics, QH426-470
Abstract: Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10−8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
Published: 2024
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2. Using polygenic risk modification to improve breast cancer prevention: study protocol for the PRiMo multicentre randomised controlled trial

Author: Melissa C Southey, Georgia Chenevix-Trench, Paul A James, Simone McInerny, Lyon Mascarenhas, Tatiane Yanes, Lara Petelin, and Mary-Anne Young
Subjects: Medicine
Abstract: Introduction Established personal and familial risk factors contribute collectively to a woman’s risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to investigate these risks but recent information on the role of common genomic variants, in the form of a Polygenic Risk Score (PRS), has provided the potential to further personalise breast and ovarian cancer risk assessment. Data from cohort studies support the potential of an integrated risk assessment to improve targeted risk management but experience of this approach in clinical practice is limited.Methods and analysis The polygenic risk modification trial is an Australian multicentre prospective randomised controlled trial of integrated risk assessment including personal and family risk factors with inclusion of breast and ovarian PRS vs standard care. The study will enrol women, unaffected by cancer, undergoing predictive testing at a familial cancer clinic for a pathogenic variant in a known breast cancer (BC) or ovarian cancer (OC) predisposition gene (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D). Array-based genotyping will be used to generate breast cancer (313 SNP) and ovarian cancer (36 SNP) PRS. A suite of materials has been developed for the trial including an online portal for patient consent and questionnaires, and a clinician education programme to train healthcare providers in the use of integrated risk assessment. Long-term follow-up will evaluate differences in the assessed risk and management advice, patient risk management intentions and adherence, patient-reported experience and outcomes, and the health service implications of personalised risk assessment.Ethics and dissemination This study has been approved by the Human Research Ethics Committee of Peter MacCallum Cancer Centre and at all participating centres. Study findings will be disseminated via peer-reviewed publications and conference presentations, and directly to participants.Trial registration number ACTRN12621000009819.
Published: 2024
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3. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Author: Pooja Middha, Xiaoliang Wang, Sabine Behrens, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Thaïs Baert, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Javier Benitez, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Daniele Campa, Federico Canzian, Angel Carracedo, Jose E. Castelao, Stephen J. Chanock, Georgia Chenevix-Trench, CTS Consortium, Emilie Cordina-Duverger, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Laure Dossus, Pierre-Antoine Dugué, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine D. Figueroa, Olivia Fletcher, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Graham G. Giles, Anna González-Neira, Felix Grassmann, Anne Grundy, Pascal Guénel, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Susan E. Hankinson, Elaine F. Harkness, Bernd Holleczek, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, David J. Hunter, Christian Ingvar, ABCTB Investigators, kConFab Investigators, Karolin Isaksson, Helena Jernström, Esther M. John, Michael E. Jones, Rudolf Kaaks, Renske Keeman, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Susanna Larsson, Loic Le Marchand, Flavio Lejbkowicz, Shuai Li, Martha Linet, Jolanta Lissowska, Maria Elena Martinez, Tabea Maurer, Anna Marie Mulligan, Claire Mulot, Rachel A. Murphy, William G. Newman, Sune F. Nielsen, Børge G. Nordestgaard, Aaron Norman, Katie M. O’Brien, Janet E. Olson, Alpa V. Patel, Ross Prentice, Erika Rees-Punia, Gad Rennert, Valerie Rhenius, Kathryn J. Ruddy, Dale P. Sandler, Christopher G. Scott, Mitul Shah, Xiao-Ou Shu, Ann Smeets, Melissa C. Southey, Jennifer Stone, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Katarzyna Tomczyk, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Sophia S. Wang, Clarice R. Weinberg, Hans Wildiers, Walter Willett, Stacey J. Winham, Alicja Wolk, Xiaohong R. Yang, M. Pilar Zamora, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul D. P. Pharoah, Montserrat García-Closas, Marjanka K. Schmidt, Peter Kraft, Roger L. Milne, Sara Lindström, Douglas F. Easton, and Jenny Chang-Claude
Subjects: Breast cancer, Gene-environment interactions, Genetic epidemiology, European ancestry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability
Published: 2023
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4. PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants

Author: Taru A. Muranen, Anna Morra, Sofia Khan, Daniel R. Barnes, Manjeet K. Bolla, Joe Dennis, Renske Keeman, Goska Leslie, Michael T. Parsons, Qin Wang, Thomas U. Ahearn, Kristiina Aittomäki, Irene L. Andrulis, Banu K. Arun, Sabine Behrens, Katarzyna Bialkowska, Stig E. Bojesen, Nicola J. Camp, Jenny Chang-Claude, Kamila Czene, Peter Devilee, HEBON investigators, Susan M. Domchek, Alison M. Dunning, Christoph Engel, D. Gareth Evans, Manuela Gago-Dominguez, Montserrat García-Closas, Anne-Marie Gerdes, Gord Glendon, Pascal Guénel, Eric Hahnen, Ute Hamann, Helen Hanson, Maartje J. Hooning, Reiner Hoppe, Louise Izatt, Anna Jakubowska, Paul A. James, Vessela N. Kristensen, Fiona Lalloo, Geoffrey J. Lindeman, Arto Mannermaa, Sara Margolin, Susan L. Neuhausen, William G. Newman, Paolo Peterlongo, Kelly-Anne Phillips, Miquel Angel Pujana, Johanna Rantala, Karina Rønlund, Emmanouil Saloustros, Rita K. Schmutzler, Andreas Schneeweiss, Christian F. Singer, Maija Suvanto, Yen Yen Tan, Manuel R. Teixeira, Mads Thomassen, Marc Tischkowitz, Vishakha Tripathi, Barbara Wappenschmidt, Emily Zhao, Douglas F. Easton, Antonis C. Antoniou, Georgia Chenevix-Trench, Paul D. P. Pharoah, Marjanka K. Schmidt, Carl Blomqvist, and Heli Nevanlinna
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the prognostic estimates. The breast cancer mortality of BRCA2 carriers was underestimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was overestimated. These data suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when estimating the prognosis of ER-positive breast cancer patients.
Published: 2023
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5. CRISPR screens identify gene targets at breast cancer risk loci

Author: Natasha K. Tuano, Jonathan Beesley, Murray Manning, Wei Shi, Laura Perlaza-Jimenez, Luis F. Malaver-Ortega, Jacob M. Paynter, Debra Black, Andrew Civitarese, Karen McCue, Aaron Hatzipantelis, Kristine Hillman, Susanne Kaufmann, Haran Sivakumaran, Jose M. Polo, Roger R. Reddel, Vimla Band, Juliet D. French, Stacey L. Edwards, David R. Powell, Georgia Chenevix-Trench, and Joseph Rosenbluh
Subjects: Post GWAS, Breast cancer risk, Functional phenotypic screens, Target discovery, Biology (General), QH301-705.5, Genetics, QH426-470
Abstract: Abstract Background Genome-wide association studies (GWAS) have identified > 200 loci associated with breast cancer risk. The majority of candidate causal variants are in non-coding regions and likely modulate cancer risk by regulating gene expression. However, pinpointing the exact target of the association, and identifying the phenotype it mediates, is a major challenge in the interpretation and translation of GWAS. Results Here, we show that pooled CRISPR screens are highly effective at identifying GWAS target genes and defining the cancer phenotypes they mediate. Following CRISPR mediated gene activation or suppression, we measure proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on DNA repair. We perform 60 CRISPR screens and identify 20 genes predicted with high confidence to be GWAS targets that promote cancer by driving proliferation or modulating the DNA damage response in breast cells. We validate the regulation of a subset of these genes by breast cancer risk variants. Conclusions We demonstrate that phenotypic CRISPR screens can accurately pinpoint the gene target of a risk locus. In addition to defining gene targets of risk loci associated with increased breast cancer risk, we provide a platform for identifying gene targets and phenotypes mediated by risk variants.
Published: 2023
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6. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

Author: Christopher Hakkaart, John F. Pearson, Louise Marquart, Joe Dennis, George A. R. Wiggins, Daniel R. Barnes, Bridget A. Robinson, Peter D. Mace, Kristiina Aittomäki, Irene L. Andrulis, Banu K. Arun, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Sami Belhadj, Lieke Berger, Marinus J. Blok, Susanne E. Boonen, Julika Borde, Angela R. Bradbury, Joan Brunet, Saundra S. Buys, Maria A. Caligo, Ian Campbell, Wendy K. Chung, Kathleen B. M. Claes, GEMO Study Collaborators, EMBRACE Collaborators, Marie-Agnès Collonge-Rame, Jackie Cook, Casey Cosgrove, Fergus J. Couch, Mary B. Daly, Sita Dandiker, Rosemarie Davidson, Miguel de la Hoya, Robin de Putter, Capucine Delnatte, Mallika Dhawan, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Alan Donaldson, Jacqueline Eason, Douglas F. Easton, Hans Ehrencrona, Christoph Engel, D. Gareth Evans, Ulrike Faust, Lidia Feliubadaló, Florentia Fostira, Eitan Friedman, Megan Frone, Debra Frost, Judy Garber, Simon A. Gayther, Andrea Gehrig, Paul Gesta, Andrew K. Godwin, David E. Goldgar, Mark H. Greene, Eric Hahnen, Christopher R. Hake, Ute Hamann, Thomas V. O. Hansen, Jan Hauke, Julia Hentschel, Natalie Herold, Ellen Honisch, Peter J. Hulick, Evgeny N. Imyanitov, SWE-BRCA Investigators, kConFab Investigators, HEBON Investigators, Claudine Isaacs, Louise Izatt, Angel Izquierdo, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Vijai Joseph, Beth Y. Karlan, Zoe Kemp, Judy Kirk, Irene Konstantopoulou, Marco Koudijs, Ava Kwong, Yael Laitman, Fiona Lalloo, Christine Lasset, Charlotte Lautrup, Conxi Lazaro, Clémentine Legrand, Goska Leslie, Fabienne Lesueur, Phuong L. Mai, Siranoush Manoukian, Véronique Mari, John W. M. Martens, Lesley McGuffog, Noura Mebirouk, Alfons Meindl, Austin Miller, Marco Montagna, Lidia Moserle, Emmanuelle Mouret-Fourme, Hannah Musgrave, Sophie Nambot, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Joanne Ngeow Yuen Yie, Tu Nguyen-Dumont, Liene Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Claus-Eric Ott, Sue K. Park, Michael T. Parsons, Inge Sokilde Pedersen, Ana Peixoto, Pedro Perez-Segura, Paolo Peterlongo, Timea Pocza, Paolo Radice, Juliane Ramser, Johanna Rantala, Gustavo C. Rodriguez, Karina Rønlund, Efraim H. Rosenberg, Maria Rossing, Rita K. Schmutzler, Payal D. Shah, Saba Sharif, Priyanka Sharma, Lucy E. Side, Jacques Simard, Christian F. Singer, Katie Snape, Doris Steinemann, Dominique Stoppa-Lyonnet, Christian Sutter, Yen Yen Tan, Manuel R. Teixeira, Soo Hwang Teo, Mads Thomassen, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Alison H. Trainer, Vishakha Tripathi, Nadine Tung, Klaartje van Engelen, Elizabeth J. van Rensburg, Ana Vega, Alessandra Viel, Lisa Walker, Jeffrey N. Weitzel, Marike R. Wevers, Georgia Chenevix-Trench, Amanda B. Spurdle, Antonis C. Antoniou, and Logan C. Walker
Subjects: Biology (General), QH301-705.5
Abstract: The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.
Published: 2022
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7. Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer

Author: Jodi M. Saunus, Xavier M. De Luca, Korinne Northwood, Ashwini Raghavendra, Alexander Hasson, Amy E. McCart Reed, Malcolm Lim, Samir Lal, A. Cristina Vargas, Jamie R. Kutasovic, Andrew J. Dalley, Mariska Miranda, Emarene Kalaw, Priyakshi Kalita-de Croft, Irma Gresshoff, Fares Al-Ejeh, Julia M. W. Gee, Chris Ormandy, Kum Kum Khanna, Jonathan Beesley, Georgia Chenevix-Trench, Andrew R. Green, Emad A. Rakha, Ian O. Ellis, Dan V. Nicolau, Peter T. Simpson, and Sunil R. Lakhani
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Intratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We investigated its relevance in breast cancer by immunophenotyping 21 normal breast and 1860 tumour samples. Nuclear SOX10 was detected in normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In tumours, nuclear SOX10 was almost exclusive to TNBC, and predicted poorer outcome amongst cross-sectional (p = 0.0015, hazard ratio 2.02, n = 224) and metaplastic (p = 0.04, n = 66) cases. To understand SOX10’s influence over the transcriptome during the transition from normal to malignant states, we performed a systems-level analysis of co-expression data, de-noising the networks with an eigen-decomposition method. This identified a core module in SOX10’s normal mammary epithelial network that becomes rewired to NCSC genes in TNBC. Crucially, this reprogramming was proportional to genome-wide promoter methylation loss, particularly at lineage-specifying CpG-island shores. We propose that the progressive, genome-wide methylation loss in TNBC simulates more primitive epigenome architecture, making cells vulnerable to SOX10-driven reprogramming. This study demonstrates potential utility for SOX10 as a prognostic biomarker in TNBC and provides new insights about developmental phenotypic mimicry—a major contributor to intratumoral heterogeneity.
Published: 2022
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8. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Leila Dorling, Sara Carvalho, Jamie Allen, Michael T. Parsons, Cristina Fortuno, Anna González-Neira, Stephan M. Heijl, Muriel A. Adank, Thomas U. Ahearn, Irene L. Andrulis, Päivi Auvinen, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Michael Bremer, Ignacio Briceno, Nicola J. Camp, Archie Campbell, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, NBCS Collaborators, J. Margriet Collée, Kamila Czene, Joe Dennis, Thilo Dörk, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, Graham G. Giles, Gord Glendon, Pascal Guénel, Melanie Gündert, Andreas Hadjisavvas, Eric Hahnen, Per Hall, Ute Hamann, Elaine F. Harkness, Mikael Hartman, Frans B. L. Hogervorst, Antoinette Hollestelle, Reiner Hoppe, Anthony Howell, kConFab Investigators, SGBCC Investigators, Anna Jakubowska, Audrey Jung, Elza Khusnutdinova, Sung-Won Kim, Yon-Dschun Ko, Vessela N. Kristensen, Inge M. M. Lakeman, Jingmei Li, Annika Lindblom, Maria A. Loizidou, Artitaya Lophatananon, Jan Lubiński, Craig Luccarini, Michael J. Madsen, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Dimitrios Mavroudis, Roger L. Milne, Nur Aishah Mohd Taib, Kenneth Muir, Heli Nevanlinna, William G. Newman, Jan C. Oosterwijk, Sue K. Park, Paolo Peterlongo, Paolo Radice, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Mitul Shah, Xueling Sim, Melissa C. Southey, Harald Surowy, Maija Suvanto, Ian Tomlinson, Diana Torres, Thérèse Truong, Christi J. van Asperen, Regina Waltes, Qin Wang, Xiaohong R. Yang, Paul D. P. Pharoah, Marjanka K. Schmidt, Javier Benitez, Bas Vroling, Alison M. Dunning, Soo Hwang Teo, Anders Kvist, Miguel de la Hoya, Peter Devilee, Amanda B. Spurdle, Maaike P. G. Vreeswijk, and Douglas F. Easton
Subjects: Breast cancer, Genetic epidemiology, Risk prediction, Missense variants, Medicine, Genetics, QH426-470
Abstract: Abstract Background Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.
Published: 2022
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9. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Thomas U. Ahearn, Haoyu Zhang, Kyriaki Michailidou, Roger L. Milne, Manjeet K. Bolla, Joe Dennis, Alison M. Dunning, Michael Lush, Qin Wang, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Adinda Baten, Heiko Becher, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Federico Canzian, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, Christine L. Clarke, NBCS Collaborators, J. Margriet Collée, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Miriam Dwek, Diana M. Eccles, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Giuseppe Floris, Manuela Gago-Dominguez, Susan M. Gapstur, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Mark S. Goldberg, Anna González-Neira, Grethe I. Grenaker Alnæs, Mervi Grip, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Elaine F. Harkness, Bernadette A. M. Heemskerk-Gerritsen, Bernd Holleczek, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Anthony Howell, ABCTB Investigators, kConFab/AOCS Investigators, Milena Jakimovska, Anna Jakubowska, Esther M. John, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Saila Kauppila, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Vessela N. Kristensen, Ute Krüger, Katerina Kubelka-Sabit, Allison W. Kurian, Kyriacos Kyriacou, Diether Lambrechts, Derrick G. Lee, Annika Lindblom, Martha Linet, Jolanta Lissowska, Ana Llaneza, Wing-Yee Lo, Robert J. MacInnis, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Maria Elena Martinez, Catriona McLean, Alfons Meindl, Usha Menon, Heli Nevanlinna, William G. Newman, Jesse Nodora, Kenneth Offit, Håkan Olsson, Nick Orr, Tjoung-Won Park-Simon, Alpa V. Patel, Julian Peto, Guillermo Pita, Dijana Plaseska-Karanfilska, Ross Prentice, Kevin Punie, Katri Pylkäs, Paolo Radice, Gad Rennert, Atocha Romero, Thomas Rüdiger, Emmanouil Saloustros, Sarah Sampson, Dale P. Sandler, Elinor J. Sawyer, Rita K. Schmutzler, Minouk J. Schoemaker, Ben Schöttker, Mark E. Sherman, Xiao-Ou Shu, Snezhana Smichkoska, Melissa C. Southey, John J. Spinelli, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Diana Torres, Melissa A. Troester, Celine M. Vachon, Carolien H. M. van Deurzen, Elke M. van Veen, Philippe Wagner, Clarice R. Weinberg, Camilla Wendt, Jelle Wesseling, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Fergus J. Couch, Jacques Simard, Peter Kraft, Douglas F. Easton, Paul D. P. Pharoah, Marjanka K. Schmidt, Montserrat García-Closas, and Nilanjan Chatterjee
Subjects: Breast cancer, Etiologic heterogeneity, Genetic predisposition, Common breast cancer susceptibility variants, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate
Published: 2022
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10. Rare germline copy number variants (CNVs) and breast cancer risk

Author: Joe Dennis, Jonathan P. Tyrer, Logan C. Walker, Kyriaki Michailidou, Leila Dorling, Manjeet K. Bolla, Qin Wang, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Laura E. Beane Freeman, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Hermann Brenner, Jose E. Castelao, Jenny Chang-Claude, Georgia Chenevix-Trench, Christine L. Clarke, NBCS Collaborators, J. Margriet Collée, CTS Consortium, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Peter Devilee, Thilo Dörk, Laure Dossus, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, Graham G. Giles, Anna González-Neira, Pascal Guénel, Eric Hahnen, Christopher A. Haiman, Per Hall, Antoinette Hollestelle, Reiner Hoppe, John L. Hopper, Anthony Howell, ABCTB Investigators, kConFab/AOCS Investigators, Agnes Jager, Anna Jakubowska, Esther M. John, Nichola Johnson, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Veli-Matti Kosma, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Martha Linet, Alicja Ogrodniczak, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Dimitrios Mavroudis, Roger L. Milne, Taru A. Muranen, Rachel A. Murphy, Heli Nevanlinna, Janet E. Olson, Håkan Olsson, Tjoung-Won Park-Simon, Charles M. Perou, Paolo Peterlongo, Dijana Plaseska-Karanfilska, Katri Pylkäs, Gad Rennert, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Rana Shibli, Ann Smeets, Penny Soucy, Melissa C. Southey, Anthony J. Swerdlow, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Camilla Wendt, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Argyrios Ziogas, Jacques Simard, Alison M. Dunning, Paul D. P. Pharoah, and Douglas F. Easton
Subjects: Biology (General), QH301-705.5
Abstract: Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs.
Published: 2022
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11. TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members

Author: Rachel, Delahunty, Linh, Nguyen, Stuart, Craig, Belinda, Creighton, Dinuka, Ariyaratne, Dale W, Garsed, Elizabeth, Christie, Sian, Fereday, Lesley, Andrews, Alexandra, Lewis, Sharne, Limb, Ahwan, Pandey, Joy, Hendley, Nadia, Traficante, Natalia, Carvajal, Amanda B, Spurdle, Bryony, Thompson, Michael T, Parsons, Victoria, Beshay, Mila, Volcheck, Timothy, Semple, Richard, Lupat, Kenneth, Doig, Jiaan, Yu, Xiao Qing, Chen, Anna, Marsh, Christopher, Love, Sanela, Bilic, Maria, Beilin, Cassandra B, Nichols, Christina, Greer, Yeh Chen, Lee, Susan, Gerty, Lynette, Gill, Emma, Newton, Julie, Howard, Rachel, Williams, Christie, Norris, Andrew N, Stephens, Erin, Tutty, Courtney, Smyth, Shona, O'Connell, Thomas, Jobling, Colin J R, Stewart, Adeline, Tan, Stephen B, Fox, Nicholas, Pachter, Jason, Li, Jason, Ellul, Gisela, Mir Arnau, Mary-Anne, Young, Louisa, Gordon, Laura, Forrest, Marion, Harris, Karen, Livingstone, Jane, Hill, Georgia, Chenevix-Trench, Paul A, Cohen, Penelope M, Webb, Michael, Friedlander, Paul, James, David, Bowtell, and Kathryn, Alsop
Subjects: Male, Ovarian Neoplasms, Cancer Research, Australia, Breast Neoplasms, Pilot Projects, Carcinoma, Ovarian Epithelial, Oncology, Humans, Family, Female, Genetic Predisposition to Disease, Genetic Testing, Retrospective Studies
Abstract: PURPOSE Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.
Published: 2022
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12. The potential of Senicapoc, a KCNN4 inhibitor, for the prevention and treatment of breast cancer

Author: Christos Xiao, Mariska Miranda, Wei Shi, Jonathan Beesley, Jodi M. Saunus, Andrew Civitarese, Debra M. Black, Meagan Ruppert, Melrine Pereira, Susan Jackson, Zachary Teale, Dylan Carter-Cusack, Lauren Kalinowski, Jamie R. Kutasovic, Amy E. McCart Reed, Herlina Y. Handoko, XiaoQing Chen, Darrell Bessette, Kelli MacDonald, Sunil R. Lakhani, Georgia Chenevix-Trench, Kara Britt, and Fares Al-Ejeh
Abstract: BackgroundGenome-wide association studies have identified a breast cancer risk locus at 19q13.31. The candidate causal variants at this locus are located in the first exon ofKCNN4.KCNN4, which regulates membrane potential and Ca2+signaling, is a good candidate for drug repositioning because its inhibitor, Senicapoc, has been shown to be well tolerated in Phase-II and -III clinical trials for asthma and sickle cell anemia.MethodsWe evaluated public mRNA expression data to determine whether the allele at 19q13.31 associated with increased breast cancer risk was associated withKCNN4expression. We also used immunohistochemistry to evaluate the relationship between KCNN4 protein expression and breast cancer survival. We then used Senicapoc in two murine mammary tumor models to determine if it would delay tumor development. We also treated mice bearing 4T1 mammary tumors with Senicapoc, by subcutaneous injection and by oral gavage. Finally we used gene editing to make deletions withinKcnn4in 4T1 to determine whether Senicapoc had off-target effects on tumor growth.ResultsAnalysis of the Genotype-Tissue Expression Project showed that the allele at 19q13.31 associated with increased breast cancer risk is associated with increasedKCNN4expression, suggesting that inhibiting KCNN4 might reduce breast cancer risk. Using immunohistochemistry in a large breast cancer cohort, we found that membrane and cytoplasmic expression is a marker of poor prognosis in triple negative breast cancer. We then tested the efficacy of Senicapoc to prevent and treat breast cancer. This showed that it delays the development of mammary tumors in two murine models, and slows growth of a syngeneic (4T1) model of triple negative breast cancer. Senicapoc monotherapy showed similar efficacy to anthracycline/taxane-based chemotherapy in these studies, with a stronger effect when they were combined.ConclusionsThese results provide a rationale for clinical testing of Senicapoc for treating, and even preventing, breast cancer.
Published: 2023
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13. Supplementary Grant Support from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar
Abstract: Supplementary Grant Support
Published: 2023
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14. Supplementary Methods, Figures S1 - S3 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar
Abstract: Supplementary Figure S1. LocusZoom regional association plots for the seven new cross-cancer loci that were > 1 Mb from known index SNPs. Supplementary Figure S2A-B. Box plots showing eQTL associations between (A) rs9375701 and L3MBTL3 in normal breast and prostate tissues and (B) rs8037137 and RCCD1 in normal breast and ovarian tissues. Supplementary Figure S3. Interactions between BCL2L11 and the 32 Biocarta "Death Pathway" genes. Interactions were identified using the GeneMania server. Circles contain gene names, lines represent interactions, and the color of the line indicates a specific type of interaction as listed in the legend.
Published: 2023
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15. Supplementary Tables S1 - S10 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author: Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar
Abstract: Supplementary Table S1. Known risk loci for each cancer. Supplementary Table S2. Regions where known index SNPs for at least two of the three cancers lie within 1 Mb of each other. Supplementary Table S3. Full results from the meta-analysis of breast, ovarian, and prostate cancer showing the 18 independent loci associated at P < 10-8 with the same direction of effect across all three cancers. Supplementary Table S4. Conditional analysis of the rs1469713 (breast-ovarian-prostate cancer) signal, conditioning on the rs4808801 (breast cancer-specific) signal that was < 1 Mb away using GCTA software. Supplementary Table S5. Most significantly-associated genotyped SNP at new loci where index SNPs were imputed. Supplementary Table S6. Expression QTL analysis results from the GTEx Portal for the new cross-cancer risk loci listed in main Table 2. Supplementary Table S7. SNPs with P < 10-8 at the new cross-cancer risk loci listed in main Table 2 that overlap predicted enhancers in at least two cell types. Supplementary Table S8. HaploReg and non-coding RNA annotation of variants with P < 10-8 at the new cross-cancer risk loci listed in main Table 2. Supplementary Table S9. Eight of the 32 genes involved in induction of apoptosis through DR3 and DR4/5 Death Receptors (MSigDB: Biocarta "Death Pathway") a that were < 1 Mb away from an independent P < 10-5 index SNP in the 3-cancer meta-analysis. Supplementary Table S10. INRICH pathway analysis results for pathways with empirical P < 0.05. Apoptosis-related pathways containing BCL2L11 are shaded.
Published: 2023
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16. Data from Mutation of ERBB2 Provides a Novel Alternative Mechanism for the Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant Potential Tumors

Author: David D.L. Bowtell, Georgia Chenevix-Trench, Anna deFazio, Michael J. Birrer, Raghwa Sharma, Peter Russell, Nadia Traficante, Sian Fereday, Bianca Locandro, Lisa Simms, Nic Waddell, Richard Tothill, Anna V. Tinker, Joshy George, Jeremy M. Arnold, and Michael S. Anglesio
Abstract: Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as tumors of low malignant potential (LMP). Like their invasive counterparts, LMP tumors may be associated with extraovarian disease, for example, in the peritoneal cavity and regional lymph nodes. However, unlike typical invasive carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen in most serous carcinomas. Typically, LMP tumors are associated with KRAS and BRAF mutations. Interrogation of expression profiles in serous LMP tumors suggested overall redundancy of RAS-MAPK pathway mutations and a distinct mechanism of oncogenesis compared with high-grade ovarian carcinomas. Our findings indicate that activating mutation of the RAS-MAPK pathway in serous LMP may be present in >70% of cases compared with ∼12.5% in serous ovarian carcinomas. In addition to mutations of KRAS (18%) and BRAF (48%) mutations, ERBB2 mutations (6%), but not EGFR, are prevalent among serous LMP tumors. Based on the expression profile signature observed throughout our serous LMP cohort, we propose that RAS-MAPK pathway activation is a requirement of serous LMP tumor development and that other activators of this pathway are yet to be defined. Importantly, as few nonsurgical options exist for treatment of recurrent LMP tumors, therapeutic targeting of this pathway may prove beneficial, especially in younger patients where maintaining fertility is important. (Mol Cancer Res 2008;6(11):1678–90)
Published: 2023
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17. Supplementary Tables 1 - 4 from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author: Ellen L. Goode, Keith L. Knutson, Lara E. Sucheston, Kunle Odunsi, Roberta B. Ness, Simon A. Gayther, Paul D.P. Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel W. Cramer, Celeste Leigh Pearce, Joellen M. Schildkraut, Usha Menon, Susanne K. Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas Wentzensen, Jolanta Kupryjanczyk, Jenny Chang-Claude, Elisa V. Bandera, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Gottfried Konecny, Peter A. Fasching, Ian Campbell, Marc T. Goodman, Tanja Pejovic, Yukie T. Bean, Laura E. Hays, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W. Beckmann, Arif B. Ekici, James Paul, Robert Brown, James M. Flanagan, Philipp Harter, Andreas du Bois, Ira Schwaab, Claus K. Hogdall, Sara H. Olson, Lene Lundvall, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Petra Seibold, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Beata Spiewankiewicz, Louise A. Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubiński, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Howard Shen, Brenda Diergaarde, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van Den Berg, Kathryn L. Terry, Allison F. Vitonis, Starr M. Ramirez, Thomas A. Sellers, Catherine M. Phelan, Jennifer A. Doherty, Sharon E. Johnatty, Anna deFazio, Honglin Song, Jonathan Tyrer, Chen Wang, Kate Lawrenson, Lynn C. Hartmann, Claudia Preston, David N. Rider, Julie M. Cunningham, Brooke L. Fridley, Krista M. Goergen, Matthew J. Maurer, Matthew S. Block, Zachary C. Fogarty, Robert A. Vierkant, Ann L. Oberg, Kimberly R. Kalli, Kirsten B. Moysich, and Bridget Charbonneau
Abstract: PDF file - 157K, Supplemental Table 1. Regulatory T cell genes included in this study (N=25). Supplemental Table 2. Regulatory T cell SNPs included in this study. Supplemental Table 3. Participating invasive epithelial ovarian cancer studies. Supplemental Table 4. Association between clinical variables and overall survival.
Published: 2023
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18. Data from Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome

Author: Ellen L. Goode, Keith L. Knutson, Lara E. Sucheston, Kunle Odunsi, Roberta B. Ness, Simon A. Gayther, Paul D.P. Pharoah, Georgia Chenevix-Trench, Mary Anne Rossing, Daniel W. Cramer, Celeste Leigh Pearce, Joellen M. Schildkraut, Usha Menon, Susanne K. Kjaer, Douglas A. Levine, Jacek Gronwald, Hoda Anton Culver, Alice S. Whittemore, Beth Y. Karlan, Diether Lambrechts, Nicolas Wentzensen, Jolanta Kupryjanczyk, Jenny Chang-Claude, Elisa V. Bandera, Estrid Hogdall, Florian Heitz, Stanley B. Kaye, Gottfried Konecny, Peter A. Fasching, Ian Campbell, Marc T. Goodman, Tanja Pejovic, Yukie T. Bean, Laura E. Hays, Galina Lurie, Diana Eccles, Alexander Hein, Matthias W. Beckmann, Arif B. Ekici, James Paul, Robert Brown, James M. Flanagan, Philipp Harter, Andreas du Bois, Ira Schwaab, Claus K. Hogdall, Sara H. Olson, Lene Lundvall, Irene Orlow, Lisa E. Paddock, Anja Rudolph, Petra Seibold, Agnieszka Dansonka-Mieszkowska, Iwona K. Rzepecka, Beata Spiewankiewicz, Louise A. Brinton, Hannah Yang, Montserrat Garcia-Closas, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Christine Walsh, Jenny Lester, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Argyrios Ziogas, Jan Lubiński, Cezary Cybulski, Janusz Menkiszak, Allan Jensen, Howard Shen, Brenda Diergaarde, Susan J. Ramus, Aleksandra Gentry-Maharaj, Andrew Berchuck, Anna H. Wu, Malcolm C. Pike, David Van Den Berg, Kathryn L. Terry, Allison F. Vitonis, Starr M. Ramirez, Thomas A. Sellers, Catherine M. Phelan, Jennifer A. Doherty, Sharon E. Johnatty, Anna deFazio, Honglin Song, Jonathan Tyrer, Chen Wang, Kate Lawrenson, Lynn C. Hartmann, Claudia Preston, David N. Rider, Julie M. Cunningham, Brooke L. Fridley, Krista M. Goergen, Matthew J. Maurer, Matthew S. Block, Zachary C. Fogarty, Robert A. Vierkant, Ann L. Oberg, Kimberly R. Kalli, Kirsten B. Moysich, and Bridget Charbonneau
Abstract: The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22–1.64; P = 5.7 × 10−6], rs791587 (HR, 1.36; 95% CI, 1.17–1.57; P = 6.2 × 10−5), rs2476491 (HR, = 1.40; 95% CI, 1.19–1.64; P = 5.6 × 10−5), and rs10795763 (HR, 1.35; 95% CI, 1.17–1.57; P = 7.9 × 10−5), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54–0.82; P = 9.3 × 10−5) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR.
Published: 2023
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19. Supplementary Data from Mutation of ERBB2 Provides a Novel Alternative Mechanism for the Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant Potential Tumors

Author: David D.L. Bowtell, Georgia Chenevix-Trench, Anna deFazio, Michael J. Birrer, Raghwa Sharma, Peter Russell, Nadia Traficante, Sian Fereday, Bianca Locandro, Lisa Simms, Nic Waddell, Richard Tothill, Anna V. Tinker, Joshy George, Jeremy M. Arnold, and Michael S. Anglesio
Abstract: Supplementary Data from Mutation of ERBB2 Provides a Novel Alternative Mechanism for the Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant Potential Tumors
Published: 2023
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20. Table S8 from A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author: Jirong Long, Wei Zheng, Paul D.P. Pharoah, Thomas A. Sellers, Georgia Chenevix-Trench, Ellen L. Goode, Andrew Berchuck, Antonis C. Antoniou, Simon A. Gayther, Kristin K. Zorn, Drakoulis Yannoukakos, Anna H. Wu, Alicja Wolk, Emily White, Nicolas Wentzensen, Jeffrey N. Weitzel, Penelope M. Webb, Digna Velez Edwards, Ana Vega, Adriaan Vanderstichele, Elizabeth J. van Rensburg, Shelley S. Tworoger, Nadine Tung, Antonia Trichopoulou, Amanda E. Toland, Marc Tischkowitz, Mads Thomassen, Soo H. Teo, Manuel R. Teixeira, Anthony J. Swerdlow, Rebecca Sutphen, Amanda B. Spurdle, Melissa C. Southey, Honglin Song, Christian F. Singer, Jacques Simard, Weiva Sieh, Priyanka Sharma, Veronica W. Setiawan, Rita K. Schmutzler, Dale P. Sandler, Iwona K. Rzepecka, Mary Anne Rossing, Matti A. Rookus, Isabelle Romieu, Cristina Rodríguez-Antona, Gustavo C. Rodriguez, Harvey Risch, Gad Rennert, Susan J. Ramus, Miquel Angel Pujana, Catherine M. Phelan, Paolo Peterlongo, Tanja Pejovic, Petra H.M. Peeters, Michael T. Parsons, Sue K. Park, Ana Osorio, Håkan Olsson, Sara H. Olson, Olufunmilayo I. Olopade, Edith Olah, Kenneth Offit, Robert L. Nussbaum, Liene Nikitina-Zake, Finn C. Nielsen, Heli Nevanlinna, Susan L. Neuhausen, Marco Montagna, Francesmary Modugno, Melissa A. Merritt, Iain A. McNeish, Lesley McGuffog, Taymaa May, Amalia Mattiello, Douglas A. Levine, Fabienne Lesueur, Goska Leslie, Nhu D. Le, Ava Kwong, Susanne K. Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Beth Y. Karlan, Paul James, Anna Jakubowska, Claudine Isaacs, Evgeny N. Imyanitov, David G. Huntsman, Peter J. Hulick, Antoinette Hollestelle, Claus K. Høgdall, Michelle A.T. Hildebrandt, Florian Heitz, Ute Hamann, Jacek Gronwald, Mark H. Greene, Marc T. Goodman, David E. Goldgar, Andrew K. Godwin, Graham G. Giles, Judy Garber, Patricia A. Ganz, Eitan Friedman, George Fountzilas, Renée T. Fortner, Peter A. Fasching, Diana M. Eccles, Douglas F. Easton, Thilo Dörk, Susan M. Domchek, Orland Diez, Joe Dennis, Anna deFazio, Mary B. Daly, Daniel W. Cramer, Fergus J. Couch, Kathleen B.M. Claes, Jenny Chang-Claude, Ian Campbell, Maria A. Caligo, Trinidad Caldes, Ralf Butzow, James Brenton, Line Bjorge, Javier Benitez, Daniel R. Barnes, Rosa B. Barkardottir, Elisa V. Bandera, Banu K. Arun, Hoda Anton-Culver, Irene L. Andrulis, Kirsten B. Moysich, Jamie K. Teer, Brett M. Reid, Jennifer B. Permuth, Yian A. Chen, Hae Kyung Im, Joellen M. Schildkraut, Bingshan Li, Xingyi Guo, Lang Wu, Alicia Beeghly-Fadiel, and Yingchang Lu
Abstract: Association results between minor alleles of 467 variants incorportated in cross tissue gene expression prediction model for the gene of CRHR1.
Published: 2023
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21. Data from Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Author: Paul D.P. Pharoah, Simon A. Gayther, Matthew L. Freedman, Alvaro N.A. Monteiro, Thomas A. Sellers, Argyrios Ziogas, Wei Zheng, Hannah Yang, Anna Wu, Xifeng Wu, Yin-Ling Woo, Lynne R. Wilkens, Kristine G. Wicklund, Alice S. Whittemore, Nicolas Wentzensen, Christine Walsh, Shan Wang-Gohrke, Robert A. Vierkant, Ignace Vergote, Els Van Nieuwenhuysen, Anne M. van Altena, Shelley S. Tworoger, Ya-Yu Tsai, Agnieszka Timorek, Pamela J. Thompson, Kathryn L. Terry, Soo-Hwang Teo, Ingvild L. Tangen, Lara E. Sucheston-Campbell, Melissa C. Southey, Honglin Song, Weiva Sieh, Nadeem Siddiqui, Yurii B. Shvetsov, Xiao-Ou Shu, Ira Schwaab, Joellen M. Schildkraut, Helga B. Salvesen, Iwona K. Rzepecka, Ingo B. Runnebaum, Anja Rudolph, Joseph H. Rothstein, Mary Anne Rossing, Barry Rosen, Harvey A. Risch, Susan J. Ramus, Elizabeth M. Poole, Malcolm C. Pike, Catherine M. Phelan, Jennifer Permuth-Wey, Liisa M. Pelttari, Tanja Pejovic, Celeste Leigh Pearce, Rachel Palmieri Weber, Sandra Orsulic, Irene Orlow, Sara H. Olson, Kunle Odunsi, Heli Nevanlinna, Roberta B. Ness, Lotte Nedergaard, Steven A. Narod, Kirsten B. Moysich, Francesmary Modugno, Usha Menon, Iain A. McNeish, John R. McLaughlin, Valerie McGuire, Keitaro Matsuo, Leon Massuger, Lene Lundvall, Jan Lubinski, Karen Lu, Jolanta Lissowska, Dong Liang, Douglas A. Levine, Jenny Lester, Arto Leminen, Shashi Lele, Alice W. Lee, Nhu D. Le, Sandrina Lambrechts, Diether Lambrechts, Jolanta Kupryjanczyk, Camilla Krakstad, Lambertus A. Kiemeney, Joseph Kelley, Melissa Kellar, Linda E. Kelemen, Susanne K. Kjaer, Beth Y. Karlan, Bu-Tian Ji, Allan Jensen, James Paul, Anna Jakubowska, Edwin S. Iversen, Satoyo Hosono, Claus K. Hogdall, Estrid Hogdall, Peter Hillemanns, Michelle A.T. Hildebrandt, Florian Heitz, Alexander Hein, Philipp Harter, Patricia Harrington, Jacek Grownwald, Marc T. Goodman, Ellen L. Goode, Rosalind Glasspool, Graham G. Giles, Aleksandra Gentry-Maharaj, Yu-Tang Gao, Brooke L. Fridley, Peter A. Fasching, Arif B. Ekici, Robert P. Edwards, Douglas F. Easton, Diana Eccles, Matthias Dürst, Andreas du Bois, Thilo Dörk, Jennifer A. Doherty, Ed Dicks, Joe Dennis, Agnieszka Dansonka-Mieszkowska, Cezary Cybulski, Julie M. Cunningham, Daniel Cramer, Linda S. Cook, Zhihua Chen, Yian Ann Chen, Jenny Chang-Claude, Karen Carty, Ian Campbell, Ralf Butzow, Angela Brooks-Wilson, Louise Brinton, Natalia Bogdanova, Line Bjørge, Maria Bisogna, Andrew Berchuck, Matthias W. Beckmann, Yukie T. Bean, Elisa V. Bandera, Helen Baker, Georgia Chenevix-Trench, Natalia Antonenkova, Hoda Anton-Culver, Katja K.H. Aben, Kate Lawrenson, Qiyuan Li, Jonathan P. Tyrer, and Siddhartha P. Kar
Abstract: Background: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.Methods: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).Results: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.Conclusion: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.Impact: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. Cancer Epidemiol Biomarkers Prev; 24(10); 1574–84. ©2015 AACR.
Published: 2023
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22. Supplementary Table 4 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 70K
Published: 2023
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23. Supplementary Table 2 from Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Eitan Friedman, Antonis C. Antoniou, Georgia Chenevix-Trench, Paul D.P. Pharoah, Andrew Lee, Sue Healey, Daniel Barrowdale, Lesley McGuffog, Karoline B. Kuchenbaecker, Åke Borg, Marie Stenmark Askmalm, Hans Ehrencrona, Anna von Wachenfeldt, Johanna Rantala, Yael Laitman, Uffe Birk Jensen, Mads Thomassen, Inge Sokilde Pedersen, Anders Bojesen, Amanda Ewart Toland, Irene L. Andrulis, Sandrine Tchatchou, Gord Glendon, Anna Marie Mulligan, Gad Rennert, Phuong L. Mai, Mark H. Greene, Catherine M. Phelan, Muy-Kheng M. Tea, Georg Pfeiler, Daphne Geschwantler Kaulich, Christine Rappaport, Christian F. Singer, Andreas Berger, Vijai Joseph, Liying Zhang, Mark E. Robson, Lauren Jacobs, Marina Corines, Kenneth Offit, Csilla I. Szabo, Xianshu Wang, Noralane M. Lindor, Fergus J. Couch, Curtis Olswold, Manuel R. Teixeira, Jocelyne Chiquette, Adalgeir Arason, Grzegorz Sukiennicki, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Jacek Gronwald, Cezary Cybulski, Lidia Feliubadalo, Joan Brunet, Conxi Lazaro, Ignacio Blanco, Orland Diez, Edith Olah, J. Margriet Collée, Helena C. van Doorn, Margreet G.E.M. Ausems, Nicoline Hoogerbrugge, Maaike P.G. Vreeswijk, Annemarie H. van der Hout, Hanne E.J. Meijers-Heijboer, Theo A.M. van Os, Kristiina Aittomäki, Heli Nevanlinna, Pedro Perez Segura, Miguel de la Hoya, Larry J. Copeland, Gustavo C. Rodriguez, Michael L. Friedlander, Marion Piedmonte, Muriel Belotti, Sylvie Mazoyer, Pascal Pujol, Olivier Caron, Olga M. Sinilnikova, Nadia Boutry-Kryza, Lisa Golmard, Laurence Venat-Bouvet, Laure Barjhoux, Isabelle Coupier, Francesca Damiola, Dominique Stoppa-Lyonnet, Claude Houdayer, Capucine Delnatte, Bruno Buecher, Brigitte Bressac-de Paillerets, Shan Wang-Gohrke, Barbara Wappenschmidt, Raymonda Varon-Mateeva, Norbert Arnold, Nina Ditsch, Kerstin Rhiem, Karin Kast, Hansjoerg Plendl, Doris Steinemann, Dieter Niederacher, Christoph Engel, Christian Sutter, Andrea Gehrig, Alfons Meindl, Tom Van Maerken, Kathleen Claes, Andrew K. Godwin, Trevor Cole, Steve Ellis, Shirley V. Hodgson, Rosemarie Davidson, Radka Platte, Patrick J. Morrison, Mary E. Porteous, Mark T. Rogers, M. John Kennedy, Lucy E. Side, Louise Izatt, Lisa Walker, Julian Barwell, Julian Adlard, Marc Tischkowitz, Jackie Cook, Angela Brady, Diana Eccles, Debra Frost, D. Gareth R. Evans, Claire Foo, Carole Brewer, Alan Donaldson, Judy E. Garber, Florentia Fostira, Athanassios Vratimos, Paolo Radice, Maria Grazia Tibiletti, Aline Martayan, Laura Papi, Giuseppe Giannini, Alessandra Viel, Stefano Fortuzzi, Frederique Mariette, Filomena Ficarazzi, Monica Barile, Giulietta Scuvera, Daniela Zaffaroni, Bernard Peissel, Siranoush Manoukian, Jeffrey N. Weitzel, Kathleen R. Blazer, Edye E. Conway, Javier Benitez, Cristina Martínez-Bouzas, Ana Osorio, Lars Jønson, Bent Ejlertsen, Anne-Marie Gerdes, Thomas V.O. Hansen, Susan L. Neuhausen, Yuan Chun Ding, Elizabeth J. van Rensburg, Cecilia M. Dorfling, Ramunas Janavicius, Saundra S. Buys, David E. Goldgar, Melissa C. Southey, Alex Miron, Wendy K. Chung, Jenny Lester, Sandra Orsulic, Beth Y. Karlan, Banu K. Arun, Timothy R. Rebbeck, Susan M. Domchek, Katherine L. Nathanson, Robert L. Nussbaum, Olufunmilayo I. Olopade, Encarna B. Gómez Garcia, Anna Jakubowska, Jan Lubinski, Laura Matricardi, Marco Montagna, Ana-Teresa Maia, Felicity Lose, Logan C. Walker, Amanda B. Spurdle, Frederieke H. van der Baan, Marjanka K. Schmidt, Matti A. Rookus, Bowang Chen, Stefan Wilkening, Ute Hamann, Douglas F. Easton, Rosalind A. Eeles, Penny Soucy, Jacques Simard, Rita K. Schmutzler, Anja Rudolph, Kirsten B. Moysich, Jenny Chang-Claude, and Paolo Peterlongo
Abstract: Supplementary Table 2. Results of the statistical analyses in BRCA mutation carriers.
Published: 2023
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24. Supplementary Figure S2 from The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

Author: Neil Johnson, Violeta Serra, Judith Balmaña, Jos Jonkers, Peter Bouwman, Elizabeth M. Swisher, Mary B. Daly, Denise C. Connolly, David L. Wiest, Geoffrey I. Shapiro, Alan D. D'Andrea, Susanne K. Kjaer, Simon A. Gayther, Siegal Sadetzki, Robert Nussbaum, Martin Gore, Mark H. Greene, Javier J. Benitez, Håkan Olsson, Georgia Chenevix-Trench, Diether Lambrechts, Charlie Gourley, Beth Karlan, Paul D. P. Pharoah, Francisco J. Candido Dos Reis, Shawn F. Johnson, Maribel I. Harrell, Yong Zhang, Shane W. O'Brien, Ingrid van der Heijden, Hanneke van der Gulden, Suraj Peri, Emmanuelle Nicolas, Joseph Nacson, John J. Krais, Cristina Cruz, Andrea J. Bernhardy, and Yifan Wang
Abstract: Genetic analyses of BRCA1 mutant cell lines and PDX models.
Published: 2023
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25. Supplementary Table 1 from Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Eitan Friedman, Antonis C. Antoniou, Georgia Chenevix-Trench, Paul D.P. Pharoah, Andrew Lee, Sue Healey, Daniel Barrowdale, Lesley McGuffog, Karoline B. Kuchenbaecker, Åke Borg, Marie Stenmark Askmalm, Hans Ehrencrona, Anna von Wachenfeldt, Johanna Rantala, Yael Laitman, Uffe Birk Jensen, Mads Thomassen, Inge Sokilde Pedersen, Anders Bojesen, Amanda Ewart Toland, Irene L. Andrulis, Sandrine Tchatchou, Gord Glendon, Anna Marie Mulligan, Gad Rennert, Phuong L. Mai, Mark H. Greene, Catherine M. Phelan, Muy-Kheng M. Tea, Georg Pfeiler, Daphne Geschwantler Kaulich, Christine Rappaport, Christian F. Singer, Andreas Berger, Vijai Joseph, Liying Zhang, Mark E. Robson, Lauren Jacobs, Marina Corines, Kenneth Offit, Csilla I. Szabo, Xianshu Wang, Noralane M. Lindor, Fergus J. Couch, Curtis Olswold, Manuel R. Teixeira, Jocelyne Chiquette, Adalgeir Arason, Grzegorz Sukiennicki, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Jacek Gronwald, Cezary Cybulski, Lidia Feliubadalo, Joan Brunet, Conxi Lazaro, Ignacio Blanco, Orland Diez, Edith Olah, J. Margriet Collée, Helena C. van Doorn, Margreet G.E.M. Ausems, Nicoline Hoogerbrugge, Maaike P.G. Vreeswijk, Annemarie H. van der Hout, Hanne E.J. Meijers-Heijboer, Theo A.M. van Os, Kristiina Aittomäki, Heli Nevanlinna, Pedro Perez Segura, Miguel de la Hoya, Larry J. Copeland, Gustavo C. Rodriguez, Michael L. Friedlander, Marion Piedmonte, Muriel Belotti, Sylvie Mazoyer, Pascal Pujol, Olivier Caron, Olga M. Sinilnikova, Nadia Boutry-Kryza, Lisa Golmard, Laurence Venat-Bouvet, Laure Barjhoux, Isabelle Coupier, Francesca Damiola, Dominique Stoppa-Lyonnet, Claude Houdayer, Capucine Delnatte, Bruno Buecher, Brigitte Bressac-de Paillerets, Shan Wang-Gohrke, Barbara Wappenschmidt, Raymonda Varon-Mateeva, Norbert Arnold, Nina Ditsch, Kerstin Rhiem, Karin Kast, Hansjoerg Plendl, Doris Steinemann, Dieter Niederacher, Christoph Engel, Christian Sutter, Andrea Gehrig, Alfons Meindl, Tom Van Maerken, Kathleen Claes, Andrew K. Godwin, Trevor Cole, Steve Ellis, Shirley V. Hodgson, Rosemarie Davidson, Radka Platte, Patrick J. Morrison, Mary E. Porteous, Mark T. Rogers, M. John Kennedy, Lucy E. Side, Louise Izatt, Lisa Walker, Julian Barwell, Julian Adlard, Marc Tischkowitz, Jackie Cook, Angela Brady, Diana Eccles, Debra Frost, D. Gareth R. Evans, Claire Foo, Carole Brewer, Alan Donaldson, Judy E. Garber, Florentia Fostira, Athanassios Vratimos, Paolo Radice, Maria Grazia Tibiletti, Aline Martayan, Laura Papi, Giuseppe Giannini, Alessandra Viel, Stefano Fortuzzi, Frederique Mariette, Filomena Ficarazzi, Monica Barile, Giulietta Scuvera, Daniela Zaffaroni, Bernard Peissel, Siranoush Manoukian, Jeffrey N. Weitzel, Kathleen R. Blazer, Edye E. Conway, Javier Benitez, Cristina Martínez-Bouzas, Ana Osorio, Lars Jønson, Bent Ejlertsen, Anne-Marie Gerdes, Thomas V.O. Hansen, Susan L. Neuhausen, Yuan Chun Ding, Elizabeth J. van Rensburg, Cecilia M. Dorfling, Ramunas Janavicius, Saundra S. Buys, David E. Goldgar, Melissa C. Southey, Alex Miron, Wendy K. Chung, Jenny Lester, Sandra Orsulic, Beth Y. Karlan, Banu K. Arun, Timothy R. Rebbeck, Susan M. Domchek, Katherine L. Nathanson, Robert L. Nussbaum, Olufunmilayo I. Olopade, Encarna B. Gómez Garcia, Anna Jakubowska, Jan Lubinski, Laura Matricardi, Marco Montagna, Ana-Teresa Maia, Felicity Lose, Logan C. Walker, Amanda B. Spurdle, Frederieke H. van der Baan, Marjanka K. Schmidt, Matti A. Rookus, Bowang Chen, Stefan Wilkening, Ute Hamann, Douglas F. Easton, Rosalind A. Eeles, Penny Soucy, Jacques Simard, Rita K. Schmutzler, Anja Rudolph, Kirsten B. Moysich, Jenny Chang-Claude, and Paolo Peterlongo
Abstract: Supplementary Table 1. The 3,248 SNPs included in the study
Published: 2023
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26. Supplementary Table 2 from 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

Author: Isabel dos-Santos-Silva, Julian Peto, Qin Wang, Manjeet Humphreys, Douglas F. Easton, Minouk Schoemaker, Michael Jones, Anthony Swerdlow, Alan Ashworth, Maya Ghoussaini, Alison M. Dunning, Fiona M. Blows, Paul Pharoah, Malcolm W.R. Reed, Ian W. Brock, Simon S. Cross, Angela Cox, Jingmei Li, Jianjun Liu, Kamila Czene, Per Hall, Madeleine M.A. Tilanus-Linthorst, Agnes Jager, Antoinette Hollestelle, Maartje J. Hooning, Caroline M. Seynaeve, John W.M. Martens, Robert A.E.M. Tollenaar, Peter Devilee, Nayana Weerasooriya, Anna Marie Mulligan, Julia A. Knight, Irene L. Andrulis, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Alexander Miron, Esther M. John, Gianluca Severi, Cariona A. McLean, Laura Baglietto, Graham Giles, Janet Olson, Xianshu Wang, Celine Vachon, Fergus J. Couch, Paolo Radice, Siranoush Manoukian, Loris Bernard, Paolo Peterlongo, Sabine Behrens, Katharina Buck, Dieter Flesch-Janys, Caroline Weltens, Robert Paridaens, Ann Smeets, Diether Lambrechts, Xiaoqing Chen, Jonathan Beesley, Georgia Chenevix-Trench, Vesa Kataja, Jaana M. Hartikainen, Veli-Matti Kosma, Arto Mannermaa, Sara Margolin, Annika Lindblom, Elza Khusnutdinova, Guzel Zinnatullina, Darya Prokofyeva, Marina Bermisheva, Yuriy Rogov, Natalia Antonenkova, Natalia Bogdanova, Carl Blomqvist, Kristiina Aittomäki, Taru A. Muranen, Heli Nevanlinna, Peter Hillemanns, Michael Bremer, Peter Schürmann, Thilo Dörk, Ursula Eilber, Shan Wang-Gohrke, Jenny Chang-Claude, Thomas Brüning, Christina Justenhoven, Hiltrud Brauch, Rita K. Schmutzler, Claus R. Bartram, Michael Golatta, Alfons Meindl, Anne Langheinz, Volker Arndt, Heiko Müller, Hermann Brenner, Christina Clarke Dur, Leslie Bernstein, Argyrios Ziogas, Hoda Anton-Culver, M. Pilar Zamora, José-Ignacio Arias-Pérez, Javier Benítez, Roger L. Milne, Børge G Nordestgaard, Henrik Flyger, Sune F. Nielsen, Stig E Bojesen, Claire Mulot, Pierre Laurent-Puig, Thérèse Truong, Pascal Guénel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Barbara Burwinkel, Michael Kerin, Ian Tomlinson, Elinor J. Sawyer, Ruediger Schulz-Wendtland, Arif B. Ekici, Matthias W. Beckmann, Peter A. Fasching, Surapon Wiangnon, Arkom Chaiwerawattana, Artitaya Lophatananon, Kenneth R. Muir, Linda M. Braaf, Sten Cornelissen, Annegien Broeks, Marjanka K. Schmidt, Maryam Mahmoodi, Melissa C. Southey, Carmel Apicella, John L. Hopper, Nichola Johnson, Nick Orr, Olivia Fletcher, Frank Dudbridge, and Helen Warren
Abstract: PDF file, 70K, Availability of information on tumor morphology and receptor status for Europeans, by each included BCAC study.
Published: 2023
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27. Supplementary Figures 1-4 and extended methods from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author: Alvaro N.A. Monteiro, Simon A. Gayther, Paul D. Pharoah, Ellen L. Goode, Thomas A. Sellers, Timothy R. Hughes, Houtan Noushmehr, Gerhard A. Coetzee, Catherine M. Phelan, Susan J. Ramus, Georgia Chenevix-Trench, Harvey Risch, Sean J. Yoder, Madalene A. Earp, Ally W. Yang, Howard C. Shen, Simon G. Coetzee, Paulo C. Lyra, Renato S. Carvalho, Anxhela Gjyshi, Hamed S. Najafabadi, Dennis J. Hazelett, Kate Lawrenson, Gustavo Mendoza-Fandiño, Jonathan P. Tyrer, Nicholas T. Woods, and Melissa A. Buckley
Abstract: This file contains: Supplementary Figure 1 (Related to Figure 2): Haplotype frequency for tiles Enhancer Scanning times with multiple SNPs. Supplementary Figure 2 (Related to Figure 3): Conservation and S/MAR predicted sequences at the locus. Supplementary Figure 3: Study overview and Overlap between the set of 134 SNPs obtained through the LD-guided analysis and the set of 40 SNPs obtained through the fine mapping-guided approach. Supplementary Figure 4 (Related to Figure 5): BNC2 binds to its own promoter. Extended data and detailed methods (including QC metrics) for BNC2 ChIP-Seq.
Published: 2023
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28. Supplementary Tables 1-4 from Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Jacques Simard, Kenneth Offit, Georgia Chenevix-Trench, Douglas F. Easton, Phuong L. Mai, Mark H. Greene, Paolo Radice, Liliana Varesco, Giuseppe Giannini, Alessandra Viel, Loris Bernard, Monica Barile, Daniela Zaffaroni, Bernard Peissel, Siranoush Manoukian, Paolo Peterlongo, V. Shane Pankratz, Zachary Fredericksen, Noralane M. Lindor, Yuan Chun Ding, Susan L. Neuhausen, Amanda B. Spurdle, Marc D. Tischkowitz, Heli Nevanlinna, Taru A. Muranen, Miguel de la Hoya, Trinidad Caldes, Wolfram Heinritz, Britta Fiebig, Karin Kast, Christian Sutter, Andrea Gehrig, Helmut Deissler, Raymonda Varon-Mateeva, Dorothea Gadzicki, Sabine Preisler-Adams, Dieter Niederacher, Simone Heidemann, Norbert Arnold, Nina Ditsch, Alfons Meindl, Christoph Engel, Barbara Wappenschmidt, Rita K. Schmutzler, Ava Kwong, Orland Diez, Cecelia M. Dorfling, Elizabeth J. van Rensburg, Mary S. Beattie, Patricia A. Ganz, Soo Hwang Teo, Edith Olah, Christine S. Walsh, Beth Y. Karlan, Kunle O. Odunsi, Paul P.D. Pharoah, Simon A. Gayther, Joan Brunet, Lidia Feliubadalo, Ignacio Blanco, Conxi Lazaro, Ramunas Janavicius, Claudine Isaacs, Evgeny N. Imyanitov, Simona Agata, Marco Montagna, Amanda Ewart-Toland, Katie Wakeley, John Boggess, Wendy S. Rubinstein, Jack Basil, Kelly Phillips, Marion Piedmonte, Mark E. Robson, Kara Sarrel, Sohela Shah, Joseph Vijai, Aðalgeir Arason, Finn C. Nielsen, Thomas V.O. Hansen, Anneliese Fink-Retter, Muy-Kheng M. Tea, Christine Rappaport, Christian F. Singer, David E. Goldgar, John L. Hopper, Melissa C. Southey, Alexander Miron, Esther M. John, Wendy K. Chung, MaryBeth Terry, Mary B. Daly, Saundra S. Buys, Carrie L. Snyder, Henry T. Lynch, Linda Akloul, Capucine Delnatte, Isabelle Coupier, Pascal Pujol, Olivier Caron, Brigitte Bressac-de Paillerets, Nadia Boutry-Kryza, Mélanie Léoné, Sylvie Mazoyer, François Cornelis, Laurent Castera, Marion Fassy-Colcombet, Dominique Stoppa-Lyonnet, Andrew K. Godwin, Betsy Bove, Lucy E. Side, M. John Kennedy, Mary E. Porteous, Lisa Walker, Patrick J. Morrison, Shirley V. Hodgson, Fiona Douglas, Carole Brewer, Joan Paterson, Jackie Cook, Trevor Cole, Diana M. Eccles, Rosemarie Davidson, Julian Adlard, Rosalind A. Eeles, Chris Jacobs, D. Gareth Evans, Elena Fineberg, Radka Platte, Steve D. Ellis, Debra Frost, Susan Peock, Margreet G.E.M. Ausems, Rogier A. Oldenburg, Maartje J. Hooning, Marleen Kets, Marinus J. Blok, Juul Wijnen, Hanne E.J. Meijers-Heijboer, Flora E. van Leeuwen, Theo A. van Os, Frans B.L. Hogervorst, Ute Hamann, Javier Benitez, María Isabel Tejada, Mercedes Durán, Ana Osorio, Bohdan Górski, Cezary Cybulski, Jacek Gronwald, Tomasz Byrski, Tomasz Huzarski, Elżbieta Złowocka, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Ania Jakubowska, Susan M. Domchek, Timothy R. Rebbeck, Katherine L. Nathanson, Per Karlsson, Hans Ehrencrona, Maria Soller, Niklas Loman, Gisela Barbany-Bustinza, Anna von Wachenfeldt, Maria A. Caligo, Torben A. Kruse, Anne-Bine Skytte, Uffe Birk Jensen, Anne-Marie Gerdes, Mads Thomassen, Anna Marie Mulligan, Hilmi Ozcelik, Irene L. Andrulis, Olga M. Sinilnikova, Sue Healey, Andrew Lee, Daniel Barrowdale, Lesley McGuffog, Tomas Kirchhoff, Xianshu Wang, Xiaoqing Chen, Jonathan Beesley, Penny Soucy, Karoline B. Kuchenbaecker, Susan J. Ramus, Antonis C. Antoniou, Mia M. Gaudet, and Fergus J. Couch
Abstract: PDF file - 90K
Published: 2023
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29. Data from The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

Author: Neil Johnson, Violeta Serra, Judith Balmaña, Jos Jonkers, Peter Bouwman, Elizabeth M. Swisher, Mary B. Daly, Denise C. Connolly, David L. Wiest, Geoffrey I. Shapiro, Alan D. D'Andrea, Susanne K. Kjaer, Simon A. Gayther, Siegal Sadetzki, Robert Nussbaum, Martin Gore, Mark H. Greene, Javier J. Benitez, Håkan Olsson, Georgia Chenevix-Trench, Diether Lambrechts, Charlie Gourley, Beth Karlan, Paul D. P. Pharoah, Francisco J. Candido Dos Reis, Shawn F. Johnson, Maribel I. Harrell, Yong Zhang, Shane W. O'Brien, Ingrid van der Heijden, Hanneke van der Gulden, Suraj Peri, Emmanuelle Nicolas, Joseph Nacson, John J. Krais, Cristina Cruz, Andrea J. Bernhardy, and Yifan Wang
Abstract: Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo. Furthermore, spliceosome inhibitors reduced BRCA1-Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778–90. ©2016 AACR.
Published: 2023
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30. Supplementary Figures 1-3 from Platinum Sensitivity–Related Germline Polymorphism Discovered via a Cell-Based Approach and Analysis of Its Association with Outcome in Ovarian Cancer Patients

Author: M. Eileen Dolan, Georgia Chenevix-Trench, Anna deFazio, Beth Y. Karlan, Jenny Gross, Ignace Vergote, Evelyn Despierre, Diether Lambrechts, Jim Paul, Robert Brown, Kunle Odunsi, Matthew Grasela, Kirsten B. Moysich, Allan Jensen, Susanne K. Kjaer, Estrid Hogdall, Brooke L. Fridley, Robert A. Vierkant, Ellen L. Goode, Stuart MacGregor, Yi Lu, Nancy J. Cox, Soma Das, Yarden S. Fraiman, Peter H. O'Donnell, Shuangli Mi, Jonathan Beesley, Peixian Chen, Emily O. Kistner, Wei Zhang, Shiwei Duan, Dana Ziliak, Hae Kyung Im, Eric R. Gamazon, Sharon E. Johnatty, and R. Stephanie Huang
Abstract: PDF file - 263K
Published: 2023
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31. Supplementary Figure Legends from The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

Author: Neil Johnson, Violeta Serra, Judith Balmaña, Jos Jonkers, Peter Bouwman, Elizabeth M. Swisher, Mary B. Daly, Denise C. Connolly, David L. Wiest, Geoffrey I. Shapiro, Alan D. D'Andrea, Susanne K. Kjaer, Simon A. Gayther, Siegal Sadetzki, Robert Nussbaum, Martin Gore, Mark H. Greene, Javier J. Benitez, Håkan Olsson, Georgia Chenevix-Trench, Diether Lambrechts, Charlie Gourley, Beth Karlan, Paul D. P. Pharoah, Francisco J. Candido Dos Reis, Shawn F. Johnson, Maribel I. Harrell, Yong Zhang, Shane W. O'Brien, Ingrid van der Heijden, Hanneke van der Gulden, Suraj Peri, Emmanuelle Nicolas, Joseph Nacson, John J. Krais, Cristina Cruz, Andrea J. Bernhardy, and Yifan Wang
Abstract: Legend for Supplementary Figures S1-S6.
Published: 2023
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32. Supplementary Figures 1-5, Tables 1-8 from Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Author: Georgia Chenevix-Trench, Penelope M. Webb, Anna deFazio, Ellen L. Goode, Paul D.P. Pharoah, Stuart MacGregor, Andrew Berchuck, Yoke-Eng Chiew, Catherine Kennedy, Thomas Sellers, Rosalind Glasspool, Nadeem Siddiqui, Karen Carty, James Paul, Ian McNeish, Lene Lundvall, Claus Høgdall, Yukie Bean, Tanja Pejovic, Irene Orlow, Elisa V. Bandera, Daniel W. Cramer, Kathryn L. Terry, Edwin S. Iversen, Joellen M. Schildkraut, Robert A. Vierkant, Julie M. Cunningham, Brooke L. Fridley, Susanne Kruger Kjaer, Allan Jensen, Estrid Høgdall, Zachary C. Fogarty, Melissa C. Larson, Madalene Earp, Stacey J. Winham, Sandra Orsulic, Jenny Lester, Christine Walsh, Beth Y. Karlan, Peter Hillemanns, Jacobus Pisterer, Philipp Harter, Ira Schwaab, Andreas du Bois, Florian Heitz, Pamela J. Thompson, Michael E. Carney, Lynne R. Wilkens, Marc T. Goodman, Beata Spiewankiewicz, Iwona K. Rzepecka, Agnieszka Dansonka-Mieszkowska, Jolanta Kupryjanczyk, Anna H. Wu, Daniel O. Stram, Malcolm C. Pike, Celeste L. Pearce, Susan J. Ramus, Usha Menon, Aleksandra Gentry-Maharaj, Simon A. Gayther, Argyrios Ziogas, Hoda Anton-Culver, Rebecca Sutphen, Joseph H. Rothstein, Valerie McGuire, Alice S. Whittemore, Weiva Sieh, Diana Eccles, Ian Campbell, Valerie Rhenius, Honglin Song, Nicolas Wentzensen, Jolanta Lissowska, Louise Brinton, Cezary Cybulski, Anna Jakubowska, Jan Lubiński, Jacek Gronwald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Douglas A. Levine, Kirsten B. Moysich, Roberta B. Ness, Francesmary Modugno, Jenny Chang-Claude, Jennifer A. Doherty, Mary Anne Rossing, Sandrina Lambrechts, Ignace Vergote, Els Van Nieuwenhuysen, Diether Lambrechts, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Peter A. Fasching, Bo Gao, Yi Lu, Jonathan Beesley, Siddhartha Kar, Jonathan P. Tyrer, and Sharon E. Johnatty
Abstract: Supplementary Figures 1-5, Tables 1-8. Supplementary Figure 1: Overview of the analytic approach. Supplementary Figure 2: QQ plots of SNPs with MAF â‰¥0.02 and imputation r2 â‰¥0.9 associated with Overall Survival in A. Supplementary Figure 3: â€˜All OCACâ€™ histology-adjusted analysis. Supplementary Figure 4: Forest plots of promising SNPs. Supplementary Figure 5: KM-Plotter graphs of significant associations with outcome. Supplementary Table 1: All studies (OCAC & TCGA) eligible for analyses according to first-line chemotherapy. Supplementary Table 2: Description of individual OCAC studies included in the secondary 'all OCAC' analysis. Supplementary Table 3a: Overall Survival estimates for selected SNPs (MAF â‰¥0.02) comparing iCOGS imputed (r2 â‰¥0.3) and iPLEX genotyped samples. Supplementary Table 3b: Progression-free Survival estimates for selected SNPs (MAF â‰¥0.02) comparing iCOGS imputed (r2 â‰¥0.3) and iPLEX genotyped samples. Supplementary Table 4: SNPs with imputation r2 â‰¥0.9, EAF â‰¥0.02 and p â‰¤ 1E-05 for at least one of four outcomes analyzed in cases selected according to first-line chemotherapy. Supplementary Table 5: Meta-analysis of largest possible sample (TCGA, non-overlapping iCOGS and iplex genotyped) for selected promising SNPs analyzed in cases selected according to first-line chemotherapy. Supplementary Table 6: Significant association between protein-coding genes within 1Mb of promising SNPs and ovarian cancer outcomes. Supplementary Table 7: SNPs with imputation r-sqâ‰¥0.9 and p â‰¤ 1E-05 for Overall Survival in histology-adj 'all OCAC' analysis. Supplementary Table 8: iCOGS estimates for SNPs previously identified to be associated with response to chemotherapy as reported in the aNHGRI GWAS catalog.
Published: 2023
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33. Supplementary Table 1 from Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Author: Wei Zheng, Douglas F. Easton, Alison M. Dunning, Georgia Chenevix-Trench, Jacques Simard, Paul D.P. Pharoah, Per Hall, Ying Zheng, M. Pilar Zamora, Cheng Har Yip, Anna Wu, Robert Winqvist, Wanqing Wen, Ans van den Ouweland, Chiu-chen Tseng, Thérèse Truong, Ian P.M. Tomlinson, Robert A.E.M. Tollenaar, Amanda Ewart Toland, Bernard Thienpont, Soo Hwang Teo, Anthony Swerdlow, Melissa C. Southey, Martha J. Shrubsole, Jiajun Shi, Chen-Yang Shen, Rita K. Schmutzler, Marjanka K. Schmidt, Elinor J. Sawyer, Suleeporn Sangrajrang, Anja Rudolph, Thomas Choudary Putti, Paolo Peterlongo, Nick Orr, Janet E. Olson, Silje Nord, Heli Nevanlinna, Susan L. Neuhausen, Kenneth Muir, Alfons Meindl, Catriona A. McLean, Keitaro Matsuo, Frederik Marme, Sara Margolin, Siranoush Manoukian, Arto Mannermaa, Jan Lubinski, Artitaya Lophatananon, Annika Lindblom, Jingmei Li, Loic Le Marchand, Diether Lambrechts, Veli-Matti Kosma, Julia A. Knight, Sofia Khan, Daehee Kang, Maria Kabisch, Nichola Johnson, Anna Jakubowska, Hidemi Ito, Chia-Ni Hsiung, John L. Hopper, Antoinette Hollestelle, Mikael Hartman, Ute Hamann, Christopher A. Haiman, Pascal Guénel, Mervi Grip, Graham G. Giles, Montserrat García-Closas, Valerie Gaborieau, Florentia Fostira, Henrik Flyger, Olivia Fletcher, Peter A. Fasching, Thilo Dörk, Arnaud Droit, Peter Devilee, Hatef Darabi, Kamila Czene, Simon S. Cross, Angela Cox, Fergus J. Couch, Ji-Yeob Choi, Jenny Chang-Claude, Sander Canisius, Hui Cai, Barbara Burwinkel, Thomas Brüning, Annegien Broeks, Louise Brinton, Hermann Brenner, Hiltrud Brauch, Stig E. Bojesen, Natalia Bogdanova, William Blot, Javier Benitez, Alicia Beeghly-Fadiel, Matthias W. Beckmann, Volker Arndt, Hoda Anton-Culver, Irene L. Andrulis, Siddhartha P. Kar, Jonathan Beesley, Qiuyin Cai, Xiao-Ou Shu, Roger L. Milne, Qin Wang, Manjeet K. Bolla, Maya Ghoussaini, Kyriaki Michailidou, Chenjie Zeng, Jirong Long, and Xingyi Guo
Abstract: Summary results for all SNPs at the 4q24 locus associated with breast cancer risk at P
Published: 2023
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34. Data from Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Author: Wei Zheng, Douglas F. Easton, Alison M. Dunning, Georgia Chenevix-Trench, Jacques Simard, Paul D.P. Pharoah, Per Hall, Ying Zheng, M. Pilar Zamora, Cheng Har Yip, Anna Wu, Robert Winqvist, Wanqing Wen, Ans van den Ouweland, Chiu-chen Tseng, Thérèse Truong, Ian P.M. Tomlinson, Robert A.E.M. Tollenaar, Amanda Ewart Toland, Bernard Thienpont, Soo Hwang Teo, Anthony Swerdlow, Melissa C. Southey, Martha J. Shrubsole, Jiajun Shi, Chen-Yang Shen, Rita K. Schmutzler, Marjanka K. Schmidt, Elinor J. Sawyer, Suleeporn Sangrajrang, Anja Rudolph, Thomas Choudary Putti, Paolo Peterlongo, Nick Orr, Janet E. Olson, Silje Nord, Heli Nevanlinna, Susan L. Neuhausen, Kenneth Muir, Alfons Meindl, Catriona A. McLean, Keitaro Matsuo, Frederik Marme, Sara Margolin, Siranoush Manoukian, Arto Mannermaa, Jan Lubinski, Artitaya Lophatananon, Annika Lindblom, Jingmei Li, Loic Le Marchand, Diether Lambrechts, Veli-Matti Kosma, Julia A. Knight, Sofia Khan, Daehee Kang, Maria Kabisch, Nichola Johnson, Anna Jakubowska, Hidemi Ito, Chia-Ni Hsiung, John L. Hopper, Antoinette Hollestelle, Mikael Hartman, Ute Hamann, Christopher A. Haiman, Pascal Guénel, Mervi Grip, Graham G. Giles, Montserrat García-Closas, Valerie Gaborieau, Florentia Fostira, Henrik Flyger, Olivia Fletcher, Peter A. Fasching, Thilo Dörk, Arnaud Droit, Peter Devilee, Hatef Darabi, Kamila Czene, Simon S. Cross, Angela Cox, Fergus J. Couch, Ji-Yeob Choi, Jenny Chang-Claude, Sander Canisius, Hui Cai, Barbara Burwinkel, Thomas Brüning, Annegien Broeks, Louise Brinton, Hermann Brenner, Hiltrud Brauch, Stig E. Bojesen, Natalia Bogdanova, William Blot, Javier Benitez, Alicia Beeghly-Fadiel, Matthias W. Beckmann, Volker Arndt, Hoda Anton-Culver, Irene L. Andrulis, Siddhartha P. Kar, Jonathan Beesley, Qiuyin Cai, Xiao-Ou Shu, Roger L. Milne, Qin Wang, Manjeet K. Bolla, Maya Ghoussaini, Kyriaki Michailidou, Chenjie Zeng, Jirong Long, and Xingyi Guo
Abstract: Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored.Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1680–91. ©2015 AACR.
Published: 2023
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35. Data from Platinum Sensitivity–Related Germline Polymorphism Discovered via a Cell-Based Approach and Analysis of Its Association with Outcome in Ovarian Cancer Patients

Author: M. Eileen Dolan, Georgia Chenevix-Trench, Anna deFazio, Beth Y. Karlan, Jenny Gross, Ignace Vergote, Evelyn Despierre, Diether Lambrechts, Jim Paul, Robert Brown, Kunle Odunsi, Matthew Grasela, Kirsten B. Moysich, Allan Jensen, Susanne K. Kjaer, Estrid Hogdall, Brooke L. Fridley, Robert A. Vierkant, Ellen L. Goode, Stuart MacGregor, Yi Lu, Nancy J. Cox, Soma Das, Yarden S. Fraiman, Peter H. O'Donnell, Shuangli Mi, Jonathan Beesley, Peixian Chen, Emily O. Kistner, Wei Zhang, Shiwei Duan, Dana Ziliak, Hae Kyung Im, Eric R. Gamazon, Sharon E. Johnatty, and R. Stephanie Huang
Abstract: Purpose: Cell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy.Experimental Design: We conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients. Phase 1 validation was based on 377 ovarian cancer patients receiving at least four cycles of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in phase 2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas.Results: In the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (Bonferroni adjusted P < 0.05). It was found to be significantly associated with decreased PFS in phase 1 AOCS patients (Pper-allele = 2 × 10−2), with a stronger effect in the subset of women with optimally debulked tumors (Pper-allele = 4 × 10−3). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumors (Pper-allele = 9 × 10−3). However, this SNP was not significant in phase 2 validation analysis with patients from numerous cohorts.Conclusion: This study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect. Clin Cancer Res; 17(16); 5490–500. ©2011 AACR.
Published: 2023
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36. Data from Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium

Author: Ellen L. Goode, Thomas A. Sellers, Joellen M. Schildkraut, Anna H. Wu, Lynne R. Wilkens, Alice S. Whittemore, Shan Wang-Gohrke, Robert A. Vierkant, David Van Den Berg, Shelley S. Tworoger, Daniel O. Stram, Honglin Song, Susan J. Ramus, Paul D.P. Pharoah, Celeste L. Pearce, Rachel T. Palmieri, Roberta B. Ness, Kirsten Moysich, Patricia G. Moorman, Usha Menon, Galina Lurie, Susanne Krüger Kjær, Estrid Høgdall, Aleksandra Gentry-Maharaj, Simon A. Gayther, Margaret A. Gates, Brooke L. Fridley, Zachary S. Fredericksen, Douglas F. Easton, Jennifer A. Doherty, Richard A. DiCioccio, Julie M. Cunningham, Daniel W. Cramer, Georgia Chenevix-Trench, Jenny Chang-Claude, Michael E. Carney, Sony Brar, Andrew Berchuck, Jonathan Beesley, Hoda Anton-Culver, Martin Köbel, Penelope M. Webb, Mary Anne Rossing, Valerie McGuire, Marc T. Goodman, and Linda E. Kelemen
Abstract: Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type.Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site.Results: The five polymorphisms were not associated with ovarian carcinoma overall (Ptrend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; Pheterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification.Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology. Cancer Epidemiol Biomarkers Prev; 19(7); 1822–30. ©2010 AACR.
Published: 2023
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37. Data from Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

Author: Georgia Chenevix-Trench, Penelope M. Webb, Anna deFazio, Ellen L. Goode, Paul D.P. Pharoah, Stuart MacGregor, Andrew Berchuck, Yoke-Eng Chiew, Catherine Kennedy, Thomas Sellers, Rosalind Glasspool, Nadeem Siddiqui, Karen Carty, James Paul, Ian McNeish, Lene Lundvall, Claus Høgdall, Yukie Bean, Tanja Pejovic, Irene Orlow, Elisa V. Bandera, Daniel W. Cramer, Kathryn L. Terry, Edwin S. Iversen, Joellen M. Schildkraut, Robert A. Vierkant, Julie M. Cunningham, Brooke L. Fridley, Susanne Kruger Kjaer, Allan Jensen, Estrid Høgdall, Zachary C. Fogarty, Melissa C. Larson, Madalene Earp, Stacey J. Winham, Sandra Orsulic, Jenny Lester, Christine Walsh, Beth Y. Karlan, Peter Hillemanns, Jacobus Pisterer, Philipp Harter, Ira Schwaab, Andreas du Bois, Florian Heitz, Pamela J. Thompson, Michael E. Carney, Lynne R. Wilkens, Marc T. Goodman, Beata Spiewankiewicz, Iwona K. Rzepecka, Agnieszka Dansonka-Mieszkowska, Jolanta Kupryjanczyk, Anna H. Wu, Daniel O. Stram, Malcolm C. Pike, Celeste L. Pearce, Susan J. Ramus, Usha Menon, Aleksandra Gentry-Maharaj, Simon A. Gayther, Argyrios Ziogas, Hoda Anton-Culver, Rebecca Sutphen, Joseph H. Rothstein, Valerie McGuire, Alice S. Whittemore, Weiva Sieh, Diana Eccles, Ian Campbell, Valerie Rhenius, Honglin Song, Nicolas Wentzensen, Jolanta Lissowska, Louise Brinton, Cezary Cybulski, Anna Jakubowska, Jan Lubiński, Jacek Gronwald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Douglas A. Levine, Kirsten B. Moysich, Roberta B. Ness, Francesmary Modugno, Jenny Chang-Claude, Jennifer A. Doherty, Mary Anne Rossing, Sandrina Lambrechts, Ignace Vergote, Els Van Nieuwenhuysen, Diether Lambrechts, Matthias W. Beckmann, Arif B. Ekici, Alexander Hein, Peter A. Fasching, Bo Gao, Yi Lu, Jonathan Beesley, Siddhartha Kar, Jonathan P. Tyrer, and Sharon E. Johnatty
Abstract: Purpose: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome.Experimental Design: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis.Results: Five SNPs were significantly associated (P ≤ 1.0 × 10−5) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10−6). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤6 × 10−3).Conclusions: We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. Clin Cancer Res; 21(23); 5264–76. ©2015 AACR.
Published: 2023
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38. Supplementary Tables 1, 2 and 4 from Platinum Sensitivity–Related Germline Polymorphism Discovered via a Cell-Based Approach and Analysis of Its Association with Outcome in Ovarian Cancer Patients

Author: M. Eileen Dolan, Georgia Chenevix-Trench, Anna deFazio, Beth Y. Karlan, Jenny Gross, Ignace Vergote, Evelyn Despierre, Diether Lambrechts, Jim Paul, Robert Brown, Kunle Odunsi, Matthew Grasela, Kirsten B. Moysich, Allan Jensen, Susanne K. Kjaer, Estrid Hogdall, Brooke L. Fridley, Robert A. Vierkant, Ellen L. Goode, Stuart MacGregor, Yi Lu, Nancy J. Cox, Soma Das, Yarden S. Fraiman, Peter H. O'Donnell, Shuangli Mi, Jonathan Beesley, Peixian Chen, Emily O. Kistner, Wei Zhang, Shiwei Duan, Dana Ziliak, Hae Kyung Im, Eric R. Gamazon, Sharon E. Johnatty, and R. Stephanie Huang
Abstract: PDF file - 115K
Published: 2023
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39. Supplementary Table 2 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author: Alvaro N.A. Monteiro, Simon A. Gayther, Paul D. Pharoah, Ellen L. Goode, Thomas A. Sellers, Timothy R. Hughes, Houtan Noushmehr, Gerhard A. Coetzee, Catherine M. Phelan, Susan J. Ramus, Georgia Chenevix-Trench, Harvey Risch, Sean J. Yoder, Madalene A. Earp, Ally W. Yang, Howard C. Shen, Simon G. Coetzee, Paulo C. Lyra, Renato S. Carvalho, Anxhela Gjyshi, Hamed S. Najafabadi, Dennis J. Hazelett, Kate Lawrenson, Gustavo Mendoza-Fandiño, Jonathan P. Tyrer, Nicholas T. Woods, and Melissa A. Buckley
Abstract: Genes selected for NanoString analysis. Contains the following tabs: (1) Nanostring gene set: final list for NanoString analysis. Gene Symbol, genes selected for nanostring analysis; Pathway, annotation from literature or from pathways in Tab 10; Cell line, cell line (FTE, iFTSEC283; OSE, iOSE11) in which the BNC2 ChIP-Seq peak was identified in proximity to the TSS. P-value, significance of expression changes using a nominal p-value {less than or equal to} 0.05 (indicated in green highlight); (2) 995 gene list: list of 995 genes/transcripts with TSS within 30 kb of the BNC2 ChIP-Seq peak centers found in both iOSE11 and iFTSEC283 cells; (3)-(9) Coordinates and annotation of BNC2 ChIP-seq peaks and genes with TSS within 30 kb of the BNC2 ChIP-seq peak centers from two replicates each of FTE (iFTSEC283) and OSE (iOSE11) cells, their overlaps; (10) Panther GO analysis results.
Published: 2023
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40. Supplementary Table 3 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 71K
Published: 2023
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41. Supplementary Tables S1-S4 from The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

Author: Neil Johnson, Violeta Serra, Judith Balmaña, Jos Jonkers, Peter Bouwman, Elizabeth M. Swisher, Mary B. Daly, Denise C. Connolly, David L. Wiest, Geoffrey I. Shapiro, Alan D. D'Andrea, Susanne K. Kjaer, Simon A. Gayther, Siegal Sadetzki, Robert Nussbaum, Martin Gore, Mark H. Greene, Javier J. Benitez, Håkan Olsson, Georgia Chenevix-Trench, Diether Lambrechts, Charlie Gourley, Beth Karlan, Paul D. P. Pharoah, Francisco J. Candido Dos Reis, Shawn F. Johnson, Maribel I. Harrell, Yong Zhang, Shane W. O'Brien, Ingrid van der Heijden, Hanneke van der Gulden, Suraj Peri, Emmanuelle Nicolas, Joseph Nacson, John J. Krais, Cristina Cruz, Andrea J. Bernhardy, and Yifan Wang
Abstract: RNA-seq analyses of global exon splicing events (S1); Cell line therapy sensitivities (S2); Hazard ratios for survival of patients with serous ovarian carcinomas associated with BRCA1 mutation, age at diagnosis and stage (S3); Characteristics of studies included in survival analysis from Fig. 5A (S4).
Published: 2023
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42. Data from Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Jacques Simard, Kenneth Offit, Georgia Chenevix-Trench, Douglas F. Easton, Phuong L. Mai, Mark H. Greene, Paolo Radice, Liliana Varesco, Giuseppe Giannini, Alessandra Viel, Loris Bernard, Monica Barile, Daniela Zaffaroni, Bernard Peissel, Siranoush Manoukian, Paolo Peterlongo, V. Shane Pankratz, Zachary Fredericksen, Noralane M. Lindor, Yuan Chun Ding, Susan L. Neuhausen, Amanda B. Spurdle, Marc D. Tischkowitz, Heli Nevanlinna, Taru A. Muranen, Miguel de la Hoya, Trinidad Caldes, Wolfram Heinritz, Britta Fiebig, Karin Kast, Christian Sutter, Andrea Gehrig, Helmut Deissler, Raymonda Varon-Mateeva, Dorothea Gadzicki, Sabine Preisler-Adams, Dieter Niederacher, Simone Heidemann, Norbert Arnold, Nina Ditsch, Alfons Meindl, Christoph Engel, Barbara Wappenschmidt, Rita K. Schmutzler, Ava Kwong, Orland Diez, Cecelia M. Dorfling, Elizabeth J. van Rensburg, Mary S. Beattie, Patricia A. Ganz, Soo Hwang Teo, Edith Olah, Christine S. Walsh, Beth Y. Karlan, Kunle O. Odunsi, Paul P.D. Pharoah, Simon A. Gayther, Joan Brunet, Lidia Feliubadalo, Ignacio Blanco, Conxi Lazaro, Ramunas Janavicius, Claudine Isaacs, Evgeny N. Imyanitov, Simona Agata, Marco Montagna, Amanda Ewart-Toland, Katie Wakeley, John Boggess, Wendy S. Rubinstein, Jack Basil, Kelly Phillips, Marion Piedmonte, Mark E. Robson, Kara Sarrel, Sohela Shah, Joseph Vijai, Aðalgeir Arason, Finn C. Nielsen, Thomas V.O. Hansen, Anneliese Fink-Retter, Muy-Kheng M. Tea, Christine Rappaport, Christian F. Singer, David E. Goldgar, John L. Hopper, Melissa C. Southey, Alexander Miron, Esther M. John, Wendy K. Chung, MaryBeth Terry, Mary B. Daly, Saundra S. Buys, Carrie L. Snyder, Henry T. Lynch, Linda Akloul, Capucine Delnatte, Isabelle Coupier, Pascal Pujol, Olivier Caron, Brigitte Bressac-de Paillerets, Nadia Boutry-Kryza, Mélanie Léoné, Sylvie Mazoyer, François Cornelis, Laurent Castera, Marion Fassy-Colcombet, Dominique Stoppa-Lyonnet, Andrew K. Godwin, Betsy Bove, Lucy E. Side, M. John Kennedy, Mary E. Porteous, Lisa Walker, Patrick J. Morrison, Shirley V. Hodgson, Fiona Douglas, Carole Brewer, Joan Paterson, Jackie Cook, Trevor Cole, Diana M. Eccles, Rosemarie Davidson, Julian Adlard, Rosalind A. Eeles, Chris Jacobs, D. Gareth Evans, Elena Fineberg, Radka Platte, Steve D. Ellis, Debra Frost, Susan Peock, Margreet G.E.M. Ausems, Rogier A. Oldenburg, Maartje J. Hooning, Marleen Kets, Marinus J. Blok, Juul Wijnen, Hanne E.J. Meijers-Heijboer, Flora E. van Leeuwen, Theo A. van Os, Frans B.L. Hogervorst, Ute Hamann, Javier Benitez, María Isabel Tejada, Mercedes Durán, Ana Osorio, Bohdan Górski, Cezary Cybulski, Jacek Gronwald, Tomasz Byrski, Tomasz Huzarski, Elżbieta Złowocka, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Ania Jakubowska, Susan M. Domchek, Timothy R. Rebbeck, Katherine L. Nathanson, Per Karlsson, Hans Ehrencrona, Maria Soller, Niklas Loman, Gisela Barbany-Bustinza, Anna von Wachenfeldt, Maria A. Caligo, Torben A. Kruse, Anne-Bine Skytte, Uffe Birk Jensen, Anne-Marie Gerdes, Mads Thomassen, Anna Marie Mulligan, Hilmi Ozcelik, Irene L. Andrulis, Olga M. Sinilnikova, Sue Healey, Andrew Lee, Daniel Barrowdale, Lesley McGuffog, Tomas Kirchhoff, Xianshu Wang, Xiaoqing Chen, Jonathan Beesley, Penny Soucy, Karoline B. Kuchenbaecker, Susan J. Ramus, Antonis C. Antoniou, Mia M. Gaudet, and Fergus J. Couch
Abstract: Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined.Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07–1.27; P = 7.42 × 10−4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73–0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94–1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05–1.29; P = 3.8 × 10−4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10–1.52; P = 1.8 × 10−3).Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers.Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645–57. ©2012 AACR.
Published: 2023
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43. Data from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author: Alvaro N.A. Monteiro, Simon A. Gayther, Paul D. Pharoah, Ellen L. Goode, Thomas A. Sellers, Timothy R. Hughes, Houtan Noushmehr, Gerhard A. Coetzee, Catherine M. Phelan, Susan J. Ramus, Georgia Chenevix-Trench, Harvey Risch, Sean J. Yoder, Madalene A. Earp, Ally W. Yang, Howard C. Shen, Simon G. Coetzee, Paulo C. Lyra, Renato S. Carvalho, Anxhela Gjyshi, Hamed S. Najafabadi, Dennis J. Hazelett, Kate Lawrenson, Gustavo Mendoza-Fandiño, Jonathan P. Tyrer, Nicholas T. Woods, and Melissa A. Buckley
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: 2023
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44. Online Supplementary Materials from A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author: Jirong Long, Wei Zheng, Paul D.P. Pharoah, Thomas A. Sellers, Georgia Chenevix-Trench, Ellen L. Goode, Andrew Berchuck, Antonis C. Antoniou, Simon A. Gayther, Kristin K. Zorn, Drakoulis Yannoukakos, Anna H. Wu, Alicja Wolk, Emily White, Nicolas Wentzensen, Jeffrey N. Weitzel, Penelope M. Webb, Digna Velez Edwards, Ana Vega, Adriaan Vanderstichele, Elizabeth J. van Rensburg, Shelley S. Tworoger, Nadine Tung, Antonia Trichopoulou, Amanda E. Toland, Marc Tischkowitz, Mads Thomassen, Soo H. Teo, Manuel R. Teixeira, Anthony J. Swerdlow, Rebecca Sutphen, Amanda B. Spurdle, Melissa C. Southey, Honglin Song, Christian F. Singer, Jacques Simard, Weiva Sieh, Priyanka Sharma, Veronica W. Setiawan, Rita K. Schmutzler, Dale P. Sandler, Iwona K. Rzepecka, Mary Anne Rossing, Matti A. Rookus, Isabelle Romieu, Cristina Rodríguez-Antona, Gustavo C. Rodriguez, Harvey Risch, Gad Rennert, Susan J. Ramus, Miquel Angel Pujana, Catherine M. Phelan, Paolo Peterlongo, Tanja Pejovic, Petra H.M. Peeters, Michael T. Parsons, Sue K. Park, Ana Osorio, Håkan Olsson, Sara H. Olson, Olufunmilayo I. Olopade, Edith Olah, Kenneth Offit, Robert L. Nussbaum, Liene Nikitina-Zake, Finn C. Nielsen, Heli Nevanlinna, Susan L. Neuhausen, Marco Montagna, Francesmary Modugno, Melissa A. Merritt, Iain A. McNeish, Lesley McGuffog, Taymaa May, Amalia Mattiello, Douglas A. Levine, Fabienne Lesueur, Goska Leslie, Nhu D. Le, Ava Kwong, Susanne K. Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Beth Y. Karlan, Paul James, Anna Jakubowska, Claudine Isaacs, Evgeny N. Imyanitov, David G. Huntsman, Peter J. Hulick, Antoinette Hollestelle, Claus K. Høgdall, Michelle A.T. Hildebrandt, Florian Heitz, Ute Hamann, Jacek Gronwald, Mark H. Greene, Marc T. Goodman, David E. Goldgar, Andrew K. Godwin, Graham G. Giles, Judy Garber, Patricia A. Ganz, Eitan Friedman, George Fountzilas, Renée T. Fortner, Peter A. Fasching, Diana M. Eccles, Douglas F. Easton, Thilo Dörk, Susan M. Domchek, Orland Diez, Joe Dennis, Anna deFazio, Mary B. Daly, Daniel W. Cramer, Fergus J. Couch, Kathleen B.M. Claes, Jenny Chang-Claude, Ian Campbell, Maria A. Caligo, Trinidad Caldes, Ralf Butzow, James Brenton, Line Bjorge, Javier Benitez, Daniel R. Barnes, Rosa B. Barkardottir, Elisa V. Bandera, Banu K. Arun, Hoda Anton-Culver, Irene L. Andrulis, Kirsten B. Moysich, Jamie K. Teer, Brett M. Reid, Jennifer B. Permuth, Yian A. Chen, Hae Kyung Im, Joellen M. Schildkraut, Bingshan Li, Xingyi Guo, Lang Wu, Alicia Beeghly-Fadiel, and Yingchang Lu
Abstract: Online Supplementary Documents
Published: 2023
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45. Supplementary Table 1 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author: Alvaro N.A. Monteiro, Simon A. Gayther, Paul D. Pharoah, Ellen L. Goode, Thomas A. Sellers, Timothy R. Hughes, Houtan Noushmehr, Gerhard A. Coetzee, Catherine M. Phelan, Susan J. Ramus, Georgia Chenevix-Trench, Harvey Risch, Sean J. Yoder, Madalene A. Earp, Ally W. Yang, Howard C. Shen, Simon G. Coetzee, Paulo C. Lyra, Renato S. Carvalho, Anxhela Gjyshi, Hamed S. Najafabadi, Dennis J. Hazelett, Kate Lawrenson, Gustavo Mendoza-Fandiño, Jonathan P. Tyrer, Nicholas T. Woods, and Melissa A. Buckley
Abstract: Primers used in this study.
Published: 2023
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46. Supplementary Table 2 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 94K
Published: 2023
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47. Supplementary Table 3 from Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Author: Eitan Friedman, Antonis C. Antoniou, Georgia Chenevix-Trench, Paul D.P. Pharoah, Andrew Lee, Sue Healey, Daniel Barrowdale, Lesley McGuffog, Karoline B. Kuchenbaecker, Åke Borg, Marie Stenmark Askmalm, Hans Ehrencrona, Anna von Wachenfeldt, Johanna Rantala, Yael Laitman, Uffe Birk Jensen, Mads Thomassen, Inge Sokilde Pedersen, Anders Bojesen, Amanda Ewart Toland, Irene L. Andrulis, Sandrine Tchatchou, Gord Glendon, Anna Marie Mulligan, Gad Rennert, Phuong L. Mai, Mark H. Greene, Catherine M. Phelan, Muy-Kheng M. Tea, Georg Pfeiler, Daphne Geschwantler Kaulich, Christine Rappaport, Christian F. Singer, Andreas Berger, Vijai Joseph, Liying Zhang, Mark E. Robson, Lauren Jacobs, Marina Corines, Kenneth Offit, Csilla I. Szabo, Xianshu Wang, Noralane M. Lindor, Fergus J. Couch, Curtis Olswold, Manuel R. Teixeira, Jocelyne Chiquette, Adalgeir Arason, Grzegorz Sukiennicki, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Jacek Gronwald, Cezary Cybulski, Lidia Feliubadalo, Joan Brunet, Conxi Lazaro, Ignacio Blanco, Orland Diez, Edith Olah, J. Margriet Collée, Helena C. van Doorn, Margreet G.E.M. Ausems, Nicoline Hoogerbrugge, Maaike P.G. Vreeswijk, Annemarie H. van der Hout, Hanne E.J. Meijers-Heijboer, Theo A.M. van Os, Kristiina Aittomäki, Heli Nevanlinna, Pedro Perez Segura, Miguel de la Hoya, Larry J. Copeland, Gustavo C. Rodriguez, Michael L. Friedlander, Marion Piedmonte, Muriel Belotti, Sylvie Mazoyer, Pascal Pujol, Olivier Caron, Olga M. Sinilnikova, Nadia Boutry-Kryza, Lisa Golmard, Laurence Venat-Bouvet, Laure Barjhoux, Isabelle Coupier, Francesca Damiola, Dominique Stoppa-Lyonnet, Claude Houdayer, Capucine Delnatte, Bruno Buecher, Brigitte Bressac-de Paillerets, Shan Wang-Gohrke, Barbara Wappenschmidt, Raymonda Varon-Mateeva, Norbert Arnold, Nina Ditsch, Kerstin Rhiem, Karin Kast, Hansjoerg Plendl, Doris Steinemann, Dieter Niederacher, Christoph Engel, Christian Sutter, Andrea Gehrig, Alfons Meindl, Tom Van Maerken, Kathleen Claes, Andrew K. Godwin, Trevor Cole, Steve Ellis, Shirley V. Hodgson, Rosemarie Davidson, Radka Platte, Patrick J. Morrison, Mary E. Porteous, Mark T. Rogers, M. John Kennedy, Lucy E. Side, Louise Izatt, Lisa Walker, Julian Barwell, Julian Adlard, Marc Tischkowitz, Jackie Cook, Angela Brady, Diana Eccles, Debra Frost, D. Gareth R. Evans, Claire Foo, Carole Brewer, Alan Donaldson, Judy E. Garber, Florentia Fostira, Athanassios Vratimos, Paolo Radice, Maria Grazia Tibiletti, Aline Martayan, Laura Papi, Giuseppe Giannini, Alessandra Viel, Stefano Fortuzzi, Frederique Mariette, Filomena Ficarazzi, Monica Barile, Giulietta Scuvera, Daniela Zaffaroni, Bernard Peissel, Siranoush Manoukian, Jeffrey N. Weitzel, Kathleen R. Blazer, Edye E. Conway, Javier Benitez, Cristina Martínez-Bouzas, Ana Osorio, Lars Jønson, Bent Ejlertsen, Anne-Marie Gerdes, Thomas V.O. Hansen, Susan L. Neuhausen, Yuan Chun Ding, Elizabeth J. van Rensburg, Cecilia M. Dorfling, Ramunas Janavicius, Saundra S. Buys, David E. Goldgar, Melissa C. Southey, Alex Miron, Wendy K. Chung, Jenny Lester, Sandra Orsulic, Beth Y. Karlan, Banu K. Arun, Timothy R. Rebbeck, Susan M. Domchek, Katherine L. Nathanson, Robert L. Nussbaum, Olufunmilayo I. Olopade, Encarna B. Gómez Garcia, Anna Jakubowska, Jan Lubinski, Laura Matricardi, Marco Montagna, Ana-Teresa Maia, Felicity Lose, Logan C. Walker, Amanda B. Spurdle, Frederieke H. van der Baan, Marjanka K. Schmidt, Matti A. Rookus, Bowang Chen, Stefan Wilkening, Ute Hamann, Douglas F. Easton, Rosalind A. Eeles, Penny Soucy, Jacques Simard, Rita K. Schmutzler, Anja Rudolph, Kirsten B. Moysich, Jenny Chang-Claude, and Paolo Peterlongo
Abstract: Supplementary Table 3. Results of the statistical analyses of SNPs from project 12 in BRCA-mutation carriers affected or non-affected with breast cancer and according to their estrogen receptor status.
Published: 2023
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48. Data from A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author: Jirong Long, Wei Zheng, Paul D.P. Pharoah, Thomas A. Sellers, Georgia Chenevix-Trench, Ellen L. Goode, Andrew Berchuck, Antonis C. Antoniou, Simon A. Gayther, Kristin K. Zorn, Drakoulis Yannoukakos, Anna H. Wu, Alicja Wolk, Emily White, Nicolas Wentzensen, Jeffrey N. Weitzel, Penelope M. Webb, Digna Velez Edwards, Ana Vega, Adriaan Vanderstichele, Elizabeth J. van Rensburg, Shelley S. Tworoger, Nadine Tung, Antonia Trichopoulou, Amanda E. Toland, Marc Tischkowitz, Mads Thomassen, Soo H. Teo, Manuel R. Teixeira, Anthony J. Swerdlow, Rebecca Sutphen, Amanda B. Spurdle, Melissa C. Southey, Honglin Song, Christian F. Singer, Jacques Simard, Weiva Sieh, Priyanka Sharma, Veronica W. Setiawan, Rita K. Schmutzler, Dale P. Sandler, Iwona K. Rzepecka, Mary Anne Rossing, Matti A. Rookus, Isabelle Romieu, Cristina Rodríguez-Antona, Gustavo C. Rodriguez, Harvey Risch, Gad Rennert, Susan J. Ramus, Miquel Angel Pujana, Catherine M. Phelan, Paolo Peterlongo, Tanja Pejovic, Petra H.M. Peeters, Michael T. Parsons, Sue K. Park, Ana Osorio, Håkan Olsson, Sara H. Olson, Olufunmilayo I. Olopade, Edith Olah, Kenneth Offit, Robert L. Nussbaum, Liene Nikitina-Zake, Finn C. Nielsen, Heli Nevanlinna, Susan L. Neuhausen, Marco Montagna, Francesmary Modugno, Melissa A. Merritt, Iain A. McNeish, Lesley McGuffog, Taymaa May, Amalia Mattiello, Douglas A. Levine, Fabienne Lesueur, Goska Leslie, Nhu D. Le, Ava Kwong, Susanne K. Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Beth Y. Karlan, Paul James, Anna Jakubowska, Claudine Isaacs, Evgeny N. Imyanitov, David G. Huntsman, Peter J. Hulick, Antoinette Hollestelle, Claus K. Høgdall, Michelle A.T. Hildebrandt, Florian Heitz, Ute Hamann, Jacek Gronwald, Mark H. Greene, Marc T. Goodman, David E. Goldgar, Andrew K. Godwin, Graham G. Giles, Judy Garber, Patricia A. Ganz, Eitan Friedman, George Fountzilas, Renée T. Fortner, Peter A. Fasching, Diana M. Eccles, Douglas F. Easton, Thilo Dörk, Susan M. Domchek, Orland Diez, Joe Dennis, Anna deFazio, Mary B. Daly, Daniel W. Cramer, Fergus J. Couch, Kathleen B.M. Claes, Jenny Chang-Claude, Ian Campbell, Maria A. Caligo, Trinidad Caldes, Ralf Butzow, James Brenton, Line Bjorge, Javier Benitez, Daniel R. Barnes, Rosa B. Barkardottir, Elisa V. Bandera, Banu K. Arun, Hoda Anton-Culver, Irene L. Andrulis, Kirsten B. Moysich, Jamie K. Teer, Brett M. Reid, Jennifer B. Permuth, Yian A. Chen, Hae Kyung Im, Joellen M. Schildkraut, Bingshan Li, Xingyi Guo, Lang Wu, Alicia Beeghly-Fadiel, and Yingchang Lu
Abstract: Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
Published: 2023
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49. Data from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium.Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression.Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08–1.14, P = 7 × 10−18) for invasive breast cancer and 1.10 (95% CI = 1.01–1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99–1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12–1.20, P = 1 × 10−18 vs. OR = 1.03, 95% CI = 0.99–1.07, P = 0.2 for PR-negative disease; Pheterogeneity = 2 × 10−7); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14–1.25), 1.13 (1.09–1.16), and 1.04 (0.99–1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10−7].Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer.Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.
Published: 2023
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50. Supplementary Table 4 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Author: Alvaro N.A. Monteiro, Simon A. Gayther, Paul D. Pharoah, Ellen L. Goode, Thomas A. Sellers, Timothy R. Hughes, Houtan Noushmehr, Gerhard A. Coetzee, Catherine M. Phelan, Susan J. Ramus, Georgia Chenevix-Trench, Harvey Risch, Sean J. Yoder, Madalene A. Earp, Ally W. Yang, Howard C. Shen, Simon G. Coetzee, Paulo C. Lyra, Renato S. Carvalho, Anxhela Gjyshi, Hamed S. Najafabadi, Dennis J. Hazelett, Kate Lawrenson, Gustavo Mendoza-Fandiño, Jonathan P. Tyrer, Nicholas T. Woods, and Melissa A. Buckley
Abstract: Fine mapping association results. Contains univariate and conditional (conditioning on rs3814113) analysis.
Published: 2023
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