Genetic Epidemiology of Cancer

NADINE ANDRIEU

Nadine Andrieu Team co-leader Tel:

Fabienne Lesueur - Curie.fr

Fabienne Lesueur Team co-leader Tel:

Projects developed by the Genetic Epidemiology of Cancer Team (GEC) aim at characterizing genetic variants involved in familial cancers by considering effects of other genetic or non-genetic factors. In addition to variants involved in monogenic transmission, variants involved in polygenic modes of cancer inheritance are also studied, as well as their interactions with lifestyle and environmental exposures. Results from this research will in fine allow to improve risk prediction models and therefore to more precisely estimate tumor risks, which in turn will help elaborating personalized screening, follow up and new prevention strategies.

Studied populations are populations at high risk of cancer, such as Hereditary Breast and Ovary Cancer (HBOC) families, or populations having a cancer risk a priori similar to that of the general population, as in studies conducted on differentiated thyroid cancers, cancers of the digestive tracts or melanoma.

Current research on cancer-prone families focuses on pathogenic or predicted pathogenic variants in high- to moderate-risk genes such BRCA1, BRCA2, PALB2, CHEK2 and ATM, as well as on variants in other genes generally included in HBOC multigene panels, but for which the clinical utility of genetic testing still needs to be assessed. Another objective of GEC is to identify new inherited genetic factors in women with no identified pathogenic variant in the known breast cancer susceptibility genes.

To address these research questions, GEC uses multidisciplinary approaches (epidemiology, molecular genetics, biostatistics, bioinformatics) integrating data from genetics, epidemiology, clinics, high-throughput genotyping and sequencing data, as well as tumors characteristics.

Within the Team, the Platform of Investigation in Genetics and Epidemiology (PIGE) was established to support epidemiology- and genomics-related activities. The PIGE is involved in the setting up, collection and centralization of epidemiological, familial and clinical data of the national studies that we coordinate. Specifically, the PIGE participates in the development of protocols (study strategy, power calculations, logistics, etc.) and is in charge of the administrative and legal processes related to studies, organizes logistics, edits various documents (information notices and informed consent forms, questionnaires, etc.) and develops and updates the databases of each study. As examples, the PIGE is in charge of the collection and management of data of GENESIS (study on sib pairs affected with breast cancer and with no BRCA1/2 mutation), CoF-AT2 (prospective cohort of families segregating an ATM variant, including ataxia-telangiectasia families and cancer-prone families) and TUMOSPEC (nation-wide family-based study to assess cancer risks in families with a predicted pathogenic variant identified through HBOC multi-gene panel testing and to determine their associated tumor spectrum).

GEC also aims to adapt laboratory, pathology and bioinformatics-related genomic techniques to suit GEC projects’ particular needs and is endowed with a wet lab activity. Biorepositories and sample management of the GENESIS and CoF-AT2 studies, as well as of GEMO (Genetic modifiers of BRCA1/2), a DNA bank of BRCA1/2 mutation carriers established to study genetic modifiers of BRCA1 and BRCA2, are also handled in our laboratory.

The Team has established collaborations with a number of other international teams and contributes to projects conducted in the framework of several consortia, including CIMBA (Consortium of Investigators of Modifiers of BRCA1/2), BCAC (Breast Cancer Association Consortium), IBCCS (International BRCA1/2 Carriers Study), ENIGMA (Evidenced-based for the Interpretation of Germline Mutant Alleles) and EPITHYR (EPIdemiology of THYRoid cancers).

Key publications

Year of publication 2021

Juliette Coignard, Michael Lush, Jonathan Beesley, Tracy A O'Mara, Joe Dennis, Jonathan P Tyrer, Daniel R Barnes, Lesley McGuffog, Goska Leslie, Manjeet K Bolla, Muriel A Adank, Simona Agata, Thomas Ahearn, Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Norbert Arnold, Kristan J Aronson, Banu K Arun, Annelie Augustinsson, Jacopo Azzollini, Daniel Barrowdale, Caroline Baynes, Heko Becher, Marina Bermisheva, Leslie Bernstein, Katarzyna Białkowska, Carl Blomqvist, Stig E Bojesen, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S Buys, Trinidad Caldés, Maria A Caligo, Daniele Campa, Brian D Carter, Jose E Castelao, Jenny Chang-Claude, Stephen J Chanock, Wendy K Chung, Kathleen B M Claes, Christine L Clarke, , , J Margriet Collée, Don M Conroy, Kamila Czene, Mary B Daly, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M Domchek, Thilo Dörk, Isabel Dos-Santos-Silva, Alison M Dunning, Miriam Dwek, Diana M Eccles, A Heather Eliassen, Christoph Engel, Mikael Eriksson, D Gareth Evans, Peter A Fasching, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Manuela Gago-Dominguez, Susan M Gapstur, Judy Garber, Vanesa Garcia-Barberan, Montserrat García-Closas, José A García-Sáenz, Mia M Gaudet, Simon A Gayther, Andrea Gehrig, Vassilios Georgoulias, Graham G Giles, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Anna González-Neira, Mark H Greene, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Patricia A Harrington, Steven N Hart, Wei He, Frans B L Hogervorst, Antoinette Hollestelle, John L Hopper, Darling J Horcasitas, Peter J Hulick, David J Hunter, Evgeny N Imyanitov, , , , Agnes Jager, Anna Jakubowska, Paul A James, Uffe Birk Jensen, Esther M John, Michael E Jones, Rudolf Kaaks, Pooja Middha Kapoor, Beth Y Karlan, Renske Keeman, Elza Khusnutdinova, Johanna I Kiiski, Yon-Dschun Ko, Veli-Matti Kosma, Peter Kraft, Allison W Kurian, Yael Laitman, Diether Lambrechts, Loic Le Marchand, Jenny Lester, Fabienne Lesueur, Tricia Lindstrom, Adria Lopez-Fernández, Jennifer T Loud, Craig Luccarini, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, John W M Martens, Noura Mebirouk, Alfons Meindl, Austin Miller, Roger L Milne, Marco Montagna, Katherine L Nathanson, Susan L Neuhausen, Heli Nevanlinna, Finn C Nielsen, Katie M O'Brien, Olufunmilayo I Olopade, Janet E Olson, Håkan Olsson, Ana Osorio, Laura Ottini, Tjoung-Won Park-Simon, Michael T Parsons, Inge Sokilde Pedersen, Beth Peshkin, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Kelly-Anne Phillips, Eric C Polley, Bruce Poppe, Nadege Presneau, Miquel Angel Pujana, Kevin Punie, Paolo Radice, Johanna Rantala, Muhammad U Rashid, Gad Rennert, Hedy S Rennert, Mark Robson, Atocha Romero, Maria Rossing, Emmanouil Saloustros, Dale P Sandler, Regina Santella, Maren T Scheuner, Marjanka K Schmidt, Gunnar Schmidt, Christopher Scott, Priyanka Sharma, Penny Soucy, Melissa C Southey, John J Spinelli, Zoe Steinsnyder, Jennifer Stone, Dominique Stoppa-Lyonnet, Anthony Swerdlow, Rulla M Tamimi, William J Tapper, Jack A Taylor, Mary Beth Terry, Alex Teulé, Darcy L Thull, Marc Tischkowitz, Amanda E Toland, Diana Torres, Alison H Trainer, Thérèse Truong, Nadine Tung, Celine M Vachon, Ana Vega, Joseph Vijai, Qin Wang, Barbara Wappenschmidt, Clarice R Weinberg, Jeffrey N Weitzel, Camilla Wendt, Alicja Wolk, Siddhartha Yadav, Xiaohong R Yang, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Kristin K Zorn, Sue K Park, Mads Thomassen, Kenneth Offit, Rita K Schmutzler, Fergus J Couch, Jacques Simard, Georgia Chenevix-Trench, Douglas F Easton, Nadine Andrieu, Antonis C Antoniou (2021 Feb 18)

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Nature communications : 1078 : DOI : 10.1038/s41467-020-20496-3
Thérèse Truong, Fabienne Lesueur, Pierre-Emmanuel Sugier, Julie Guibon, Constance Xhaard, Mojgan Karimi, Om Kulkarni, Elise A Lucotte, Delphine Bacq-Daian, Anne Boland-Auge, Claire Mulot, Pierre Laurent-Puig, Claire Schvartz, Anne-Valérie Guizard, Yan Ren, Elisabeth Adjadj, Frédérique Rachédi, Francoise Borson-Chazot, Rosa Maria Ortiz, Juan J Lence-Anta, Celia María Pereda, Daniel F Comiskey, Huiling He, Sandya Liyanarachchi, Albert de la Chapelle, Rossella Elisei, Federica Gemignani, Hauke Thomsen, Asta Forsti, Anthony F Herzig, Anne-Louise Leutenegger, Carole Rubino, Evgenia Ostroumova, Ausrele Kesminiene, Marie-Christine Boutron-Ruault, Jean-François Deleuze, Pascal Guénel, Florent de Vathaire (2021 Feb 2)

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

International journal of cancer : DOI : 10.1002/ijc.33488
Lieske H Schrijver, Antonis C Antoniou, Håkan Olsson, Thea M Mooij, Marie-José Roos-Blom, Leyla Azarang, Julian Adlard, Munaza Ahmed, Daniel Barrowdale, Rosemarie Davidson, Alan Donaldson, Ros Eeles, D Gareth Evans, Debra Frost, Alex Henderson, Louise Izatt, Kai-Ren Ong, Valérie Bonadona, Isabelle Coupier, Laurence Faivre, Jean-Pierre Fricker, Paul Gesta, Klaartje van Engelen, Agnes Jager, Fred H Menko, Marian J E Mourits, Christian F Singer, Yen Y Tan, Lenka Foretova, Marie Navratilova, Rita K Schmutzler, Carolina Ellberg, Anne-Marie Gerdes, Trinidad Caldes, Jacques Simard, Edith Olah, Anna Jakubowska, Johanna Rantala, Ana Osorio, John L Hopper, Kelly-Anne Phillips, Roger L Milne, Mary Beth Terry, Catherine Noguès, Christoph Engel, Karin Kast, David E Goldgar, Flora E van Leeuwen, Douglas F Easton, Nadine Andrieu, Matti A Rookus, (2021 Jan 25)

Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study.

American journal of obstetrics and gynecology : DOI : S0002-9378(21)00038-7

Year of publication 2020

Christine Lonjou, Séverine Eon-Marchais, Thérèse Truong, Marie-Gabrielle Dondon, Mojgan Karimi, Yue Jiao, Francesca Damiola, Laure Barjhoux, Dorothée Le Gal, Juana Beauvallet, Noura Mebirouk, Eve Cavaciuti, Jean Chiesa, Anne Floquet, Séverine Audebert-Bellanger, Sophie Giraud, Thierry Frebourg, Jean-Marc Limacher, Laurence Gladieff, Isabelle Mortemousque, Hélène Dreyfus, Sophie Lejeune-Dumoulin, Christine Lasset, Laurence Venat-Bouvet, Yves-Jean Bignon, Pascal Pujol, Christine M Maugard, Elisabeth Luporsi, Valérie Bonadona, Catherine Noguès, Pascaline Berthet, Capucine Delnatte, Paul Gesta, Alain Lortholary, Laurence Faivre, Bruno Buecher, Olivier Caron, Marion Gauthier-Villars, Isabelle Coupier, Sylvie Mazoyer, Luis-Cristobal Monraz, Maria Kondratova, Inna Kuperstein, Pascal Guénel, Emmanuel Barillot, Dominique Stoppa-Lyonnet, Nadine Andrieu, Fabienne Lesueur (2020 Dec 28)

Gene- and pathway-level analyses of iCOGS variants highlight novel signaling pathways underlying familial breast cancer susceptibility.

International journal of cancer : 1895-1909 : DOI : 10.1002/ijc.33457
Ombretta Melaiu, Angelica Macauda, Juan Sainz, Diego Calvetti, Maria Sole Facioni, Giuseppe Maccari, Rob Ter Horst, Mihai G Netea, Yang Li, Norbert Grząśko, Victor Moreno, Artur Jurczyszyn, Andrés Jerez, Marzena Watek, Judit Varkonyi, Ramon Garcia-Sanz, Marcin Kruszewski, Marek Dudziński, Katalin Kadar, Svend Erik Hove Jacobsen, Grzegorz Mazur, Vibeke Andersen, Malwina Rybicka, Daria Zawirska, Malgorzata Raźny, Jan Maciej Zaucha, Olga Ostrovsky, Elzbieta Iskierka-Jazdzewska, Rui Manuel Reis, Anna Stępień, Katia Beider, Arnon Nagler, Agnieszka Druzd-Sitek, Herlander Marques, Joaquin Martìnez-Lopez, Fabienne Lesueur, Hervé Avet-Loiseau, Annette Juul Vangsted, Malgorzata Krawczyk-Kulis, Aleksandra Butrym, Krzysztof Jamroziak, Charles Dumontet, Ulla Vogel, Marcin Rymko, Matteo Pelosini, Edyta Subocz, Gergely Szombath, Maria Eugenia Sarasquete, Roberto Silvestri, Federica Morani, Stefano Landi, Daniele Campa, Federico Canzian, Federica Gemignani (2020 Nov 5)

Common gene variants within 3′-untranslated regions as modulators of multiple myeloma risk and survival.

International journal of cancer : 1887-1894 : DOI : 10.1002/ijc.33377
Marion Dhooge, Stéphanie Baert-Desurmont, Carole Corsini, Olivier Caron, Nadine Andrieu, Pascaline Berthet, Valérie Bonadona, Odile Cohen-Haguenauer, Antoine De Pauw, Capucine Delnatte, Sophie Dussart, Christine Lasset, Dominique Leroux, Christine Maugard, Jessica Moretta-Serra, Cornel Popovici, Bruno Buecher, Chrystelle Colas, Catherine Noguès, (2020 Oct 11)

National recommendations of the French Genetics and Cancer Group – Unicancer on the modalities of multi-genes panel analyses in hereditary predispositions to tumors of the digestive tract.

European journal of medical genetics : 104080 : DOI : S1769-7212(20)30790-4
All publications