Publications de l'équipe - Épidémiologie génétique des cancers - Centre de Recherche Institut Curie
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Publications de l’équipe
Épidémiologie génétique des cancers
Année de 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,
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1Publications de l’équipe
Épidémiologie génétique des cancers
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
Résumé
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial
factors. About 50 common variants have been shown to modify BC risk for mutation carriers.
All but three, were identified in general population studies. Other mutation carrier-specific
susceptibility variants may exist but studies of mutation carriers have so far been
underpowered. We conduct a novel case-only genome-wide association study comparing
genotype frequencies between 60,212 general population BC cases and 13,007 cases with
BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for
BRCA1 and 3 for BRCA2 mutation carriers, P < 10, at 5 loci, which are not associated with risk
in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1,
genes previously implicated in BC biology, are predicted as potential targets. These findings
will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation
carriers.
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
Résumé
Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic
groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers
with the highest familial risk suggesting a major role of genetic risk factors, but only few
susceptibility loci were identified so far. In order to assess the contribution of known DTC
susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide
association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2Publications de l’équipe
Épidémiologie génétique des cancers
Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301
cases/348 controls of Oceanian ancestry from seven population-based case-control studies
participating to the EPITHYR consortium. All participants were genotyped using the
OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC
susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population
and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-
stimulating hormone levels in previous GWAS. We additionally replicated an association with
5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all
associations were in the same direction in the population of Oceanian ancestry. We also
observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly
higher in Oceanians than in Europeans. However, additional GWAS and epidemiological
studies in Oceanian populations are needed to fully understand the highest incidence
observed in these populations.
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
Résumé
Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with
longer duration of oral contraceptive use. Although the effects of using oral contraceptives in
the general population are well established (approximately 50% risk reduction in ovarian
cancer), the estimated risk reduction in mutation carriers is much less precise because of
potential bias and small sample sizes. In addition, only a few studies on oral contraceptive
use have examined the associations of duration of use, time since last use, starting age, and
calendar year of start with risk of ovarian cancer.
Année de 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
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 3Publications de l’équipe
Épidémiologie génétique des cancers
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
Résumé
Single-nucleotide polymorphisms (SNPs) in over 180 loci have been associated with breast
cancer (BC) through genome-wide association studies involving mostly unselected
population-based case-control series. Some of them modify BC risk of women carrying a
BRCA1 or BRCA2 (BRCA1/2) mutation and may also explain BC risk variability in BC-prone
families with no BRCA1/2 mutation. Here, we assessed the contribution of SNPs of the iCOGS
array in GENESIS consisting of BC cases with no BRCA1/2 mutation and a sister with BC, and
population controls. Genotyping data were available for 1281 index cases, 731 sisters with
BC, 457 unaffected sisters and 1272 controls. In addition to the standard SNP-level analysis
using index cases and controls, we performed pedigree-based association tests to capture
transmission information in the sibships. We also performed gene- and pathway-level
analyses to maximize the power to detect associations with lower-frequency SNPs or those
with modest effect sizes. While SNP-level analyses identified 18 loci, gene-level analyses
identified 112 genes. Furthermore, 31 Kyoto Encyclopedia of Genes and Genomes and 7
Atlas of Cancer Signaling Network pathways were highlighted (false discovery rate of 5%).
Using results from the « index case-control » analysis, we built pathway-derived polygenic
risk scores (PRS) and assessed their performance in the population-based CECILE study and
in a data set composed of GENESIS-affected sisters and CECILE controls. Although these PRS
had poor predictive value in the general population, they performed better than a PRS built
using our SNP-level findings, and we found that the joint effect of family history and PRS
needs to be considered in risk prediction models.
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
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 4Publications de l’équipe
Épidémiologie génétique des cancers
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
Résumé
We evaluated the association between germline genetic variants located within the 3′-
untranlsated region (polymorphic 3’UTR, ie, p3UTR) of candidate genes involved in multiple
myeloma (MM). We performed a case-control study within the International Multiple Myeloma
rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited
from eight countries. We selected p3UTR of six genes known to act in different pathways
relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434),
SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496
was associated with increased risk of developing MM and with a worse overall survival of MM
patients. The variant allele was assayed in a vector expressing eGFP chimerized with the
IL10 3′-UTR and it was found functionally active following transfection in human myeloma
cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this
was also in agreement with the in vivo expression of mRNA measured in whole blood as
reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-
rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical
implications for better characterization of MM patients in terms of prognosis.
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
Résumé
In case of suspected hereditary predisposition to digestive cancers, next-generation
sequencing can analyze simultaneously several genes associated with an increased risk of
developing these tumors. Thus, « Gastro Intestinal » (GI) gene panels are commonly used in
French molecular genetic laboratories. Lack of international recommendations led to
disparities in the composition of these panels and in the management of patients. To
harmonize practices, the Genetics and Cancer Group (GGC)-Unicancer set up a working
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 5Publications de l’équipe
Épidémiologie génétique des cancers
group who carried out a review of the literature for 31 genes of interest in this context and
established a list of genes for which the estimated risks associated with pathogenic variant
seemed sufficiently reliable and high for clinical use. Pancreatic cancer susceptibility genes
have been excluded. This expertise defined a panel of 14 genes of confirmed clinical interest
and relevant for genetic counseling: APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6,
MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4 and STK11. The reasons for the exclusion of the
others 23 genes have been discussed. The paucity of estimates of the associated tumor risks
led to the exclusion of genes, in particular CTNNA1, MSH3 and NTHL1, despite their
implication in the molecular pathways involved in the pathophysiology of GI cancers. A
regular update of the literature is planned to up-grade this panel of genes in case of new
data on candidate genes. Genetic and epidemiological studies and international
collaborations are needed to better estimate the risks associated with the pathogenic
variants of these genes either selected or not in the current panel.
Daniel R Barnes, Matti A Rookus, Lesley McGuffog, Goska Leslie, Thea M Mooij, Joe Dennis, Nasim
Mavaddat, Julian Adlard, Munaza Ahmed, Kristiina Aittomäki, Nadine Andrieu, Irene L Andrulis,
Norbert Arnold, Banu K Arun, Jacopo Azzollini, Judith Balmaña, Rosa B Barkardottir, Daniel
Barrowdale, Javier Benitez, Pascaline Berthet, Katarzyna Białkowska, Amie M Blanco, Marinus J
Blok, Bernardo Bonanni, Susanne E Boonen, Åke Borg, Aniko Bozsik, Angela R Bradbury, Paul
Brennan, Carole Brewer, Joan Brunet, Saundra S Buys, Trinidad Caldés, Maria A Caligo, Ian
Campbell, Lise Lotte Christensen, Wendy K Chung, Kathleen B M Claes, Chrystelle Colas, , ,
Marie-Agnès Collonge-Rame, Jackie Cook, Mary B Daly, Rosemarie Davidson, Miguel de la Hoya,
Robin de Putter, Capucine Delnatte, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M
Domchek, Cecilia M Dorfling, Martine Dumont, Ros Eeles, Bent Ejlertsen, Christoph Engel, D
Gareth Evans, Laurence Faivre, Lenka Foretova, Florentia Fostira, Michael Friedlander, Eitan
Friedman, Debra Frost, Patricia A Ganz, Judy Garber, Andrea Gehrig, Anne-Marie Gerdes, Paul
Gesta, Sophie Giraud, Gord Glendon, Andrew K Godwin, David E Goldgar, Anna González-Neira,
Mark H Greene, Daphne Gschwantler-Kaulich, Eric Hahnen, Ute Hamann, Helen Hanson, Julia
Hentschel, Frans B L Hogervorst, Maartje J Hooning, Judit Horvath, Chunling Hu, Peter J Hulick,
Evgeny N Imyanitov, , , , Claudine Isaacs, Louise Izatt, Angel Izquierdo, Anna Jakubowska, Paul A
James, Ramunas Janavicius, Esther M John, Vijai Joseph, Beth Y Karlan, Karin Kast, Marco Koudijs,
Torben A Kruse, Ava Kwong, Yael Laitman, Christine Lasset, Conxi Lazaro, Jenny Lester, Fabienne
Lesueur, Annelie Liljegren, Jennifer T Loud, Jan Lubiński, Phuong L Mai, Siranoush Manoukian,
Véronique Mari, Noura Mebirouk, Hanne E J Meijers-Heijboer, Alfons Meindl, Arjen R
Mensenkamp, Austin Miller, Marco Montagna, Emmanuelle Mouret-Fourme, Semanti Mukherjee,
Anna Marie Mulligan, Katherine L Nathanson, Susan L Neuhausen, Heli Nevanlinna, Dieter
Niederacher, Finn Cilius Nielsen, Liene Nikitina-Zake, Catherine Noguès, Edith Olah,
Olufunmilayo I Olopade, Kai-Ren Ong, Aoife O'Shaughnessy-Kirwan, Ana Osorio, Claus-Eric Ott,
Laura Papi, Sue K Park, Michael T Parsons, Inge Sokilde Pedersen, Bernard Peissel, Ana Peixoto,
Paolo Peterlongo, Georg Pfeiler, Kelly-Anne Phillips, Karolina Prajzendanc, Miquel Angel Pujana,
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 6Publications de l’équipe
Épidémiologie génétique des cancers
Paolo Radice, Juliane Ramser, Susan J Ramus, Johanna Rantala, Gad Rennert, Harvey A Risch,
Mark Robson, Karina Rønlund, Ritu Salani, Hélène Schuster, Leigha Senter, Payal D Shah,
Priyanka Sharma, Lucy E Side, Christian F Singer, Thomas P Slavin, Penny Soucy, Melissa C
Southey, Amanda B Spurdle, Doris Steinemann, Zoe Steinsnyder, Dominique Stoppa-Lyonnet,
Christian Sutter, Yen Yen Tan, Manuel R Teixeira, Soo Hwang Teo, Darcy L Thull, Marc
Tischkowitz, Silvia Tognazzo, Amanda E Toland, Alison H Trainer, Nadine Tung, Klaartje van
Engelen, Elizabeth J van Rensburg, Ana Vega, Jeroen Vierstraete, Gabriel Wagner, Lisa Walker,
Shan Wang-Gohrke, Barbara Wappenschmidt, Jeffrey N Weitzel, Siddhartha Yadav, Xin Yang,
Drakoulis Yannoukakos, Dario Zimbalatti, Kenneth Offit, Mads Thomassen, Fergus J Couch, Rita K
Schmutzler, Jacques Simard, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou,
(2020 Jul 16)
Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers
of BRCA1 and BRCA2 pathogenic variants.
Genetics in medicine : official journal of the American College of Medical Genetics : 1653-1666 :
DOI : 10.1038/s41436-020-0862-x
Résumé
We assessed the associations between population-based polygenic risk scores (PRS) for
breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2
pathogenic variant carriers.
Valentina Silvestri, Goska Leslie, Daniel R Barnes, , Bjarni A Agnarsson, Kristiina Aittomäki, Elisa
Alducci, Irene L Andrulis, Rosa B Barkardottir, Alicia Barroso, Daniel Barrowdale, Javier Benitez,
Bernardo Bonanni, Ake Borg, Saundra S Buys, Trinidad Caldés, Maria A Caligo, Carlo Capalbo, Ian
Campbell, Wendy K Chung, Kathleen B M Claes, Sarah V Colonna, Laura Cortesi, Fergus J Couch,
Miguel de la Hoya, Orland Diez, Yuan Chun Ding, Susan Domchek, Douglas F Easton, Bent
Ejlertsen, Christoph Engel, D Gareth Evans, Lidia Feliubadalò, Lenka Foretova, Florentia Fostira,
Lajos Géczi, Anne-Marie Gerdes, Gord Glendon, Andrew K Godwin, David E Goldgar, Eric Hahnen,
Frans B L Hogervorst, John L Hopper, Peter J Hulick, Claudine Isaacs, Angel Izquierdo, Paul A
James, Ramunas Janavicius, Uffe Birk Jensen, Esther M John, Vijai Joseph, Irene Konstantopoulou,
Allison W Kurian, Ava Kwong, Elisabetta Landucci, Fabienne Lesueur, Jennifer T Loud, Eva
Machackova, Phuong L Mai, Keivan Majidzadeh-A, Siranoush Manoukian, Marco Montagna, Lidia
Moserle, Anna Marie Mulligan, Katherine L Nathanson, Heli Nevanlinna, Joanne Ngeow, Liene
Nikitina-Zake, Kenneth Offit, Edith Olah, Olufunmilayo I Olopade, Ana Osorio, Laura Papi, Sue K
Park, Inge Sokilde Pedersen, Pedro Perez-Segura, Annabeth H Petersen, Pedro Pinto, Berardino
Porfirio, Miquel Angel Pujana, Paolo Radice, Johanna Rantala, Muhammad U Rashid, Barak
Rosenzweig, Maria Rossing, Marta Santamariña, Rita K Schmutzler, Leigha Senter, Jacques
Simard, Christian F Singer, Angela R Solano, Melissa C Southey, Linda Steele, Zoe Steinsnyder,
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 7Publications de l’équipe
Épidémiologie génétique des cancers
Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R Teixeira, Soo H Teo, Mary Beth Terry, Mads
Thomassen, Amanda E Toland, Sara Torres-Esquius, Nadine Tung, Christi J van Asperen, Ana
Vega, Alessandra Viel, Jeroen Vierstraete, Barbara Wappenschmidt, Jeffrey N Weitzel, Greet
Wieme, Sook-Yee Yoon, Kristin K Zorn, Lesley McGuffog, Michael T Parsons, Ute Hamann, Mark H
Greene, Judy A Kirk, Susan L Neuhausen, Timothy R Rebbeck, Marc Tischkowitz, Georgia
Chenevix-Trench, Antonis C Antoniou, Eitan Friedman, Laura Ottini (2020 Jul 3)
Characterization of the Cancer Spectrum in Men With Germline BRCA1 and
BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of
Modifiers of BRCA1/2 (CIMBA).
JAMA oncology : 1218-1230 : DOI : 10.1001/jamaoncol.2020.2134
Résumé
The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic
variants (PVs) have hampered the development of evidence-based recommendations for
early cancer detection and risk reduction in this population.
Samir S Taneja (2020 Jun 27)
Re: Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer
Risk and Aggressiveness.
The Journal of urology : 619-620 : DOI : 10.1097/JU.0000000000001176.01
Résumé
Haoyu Zhang, Thomas U Ahearn, Julie Lecarpentier, Daniel Barnes, Jonathan Beesley, Guanghao
Qi, Xia Jiang, Tracy A O'Mara, Ni Zhao, Manjeet K Bolla, Alison M Dunning, Joe Dennis, Qin Wang,
Zumuruda Abu Ful, Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan
J Aronson, Banu K Arun, Paul L Auer, Jacopo Azzollini, Daniel Barrowdale, Heiko Becher, Matthias
W Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Bialkowska, Ana
Blanco, Carl Blomqvist, Natalia V Bogdanova, Stig E Bojesen, Bernardo Bonanni, Davide
Bondavalli, Ake Borg, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Annegien Broeks, Sara
Y Brucker, Thomas Brüning, Barbara Burwinkel, Saundra S Buys, Helen Byers, Trinidad Caldés,
Maria A Caligo, Mariarosaria Calvello, Daniele Campa, Jose E Castelao, Jenny Chang-Claude,
Stephen J Chanock, Melissa Christiaens, Hans Christiansen, Wendy K Chung, Kathleen B M Claes,
Christine L Clarke, Sten Cornelissen, Fergus J Couch, Angela Cox, Simon S Cross, Kamila Czene,
Mary B Daly, Peter Devilee, Orland Diez, Susan M Domchek, Thilo Dörk, Miriam Dwek, Diana M
Eccles, Arif B Ekici, D Gareth Evans, Peter A Fasching, Jonine Figueroa, Lenka Foretova, Florentia
Fostira, Eitan Friedman, Debra Frost, Manuela Gago-Dominguez, Susan M Gapstur, Judy Garber,
José A García-Sáenz, Mia M Gaudet, Simon A Gayther, Graham G Giles, Andrew K Godwin, Mark S
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 8Publications de l’équipe
Épidémiologie génétique des cancers
Goldberg, David E Goldgar, Anna González-Neira, Mark H Greene, Jacek Gronwald, Pascal
Guénel, Lothar Häberle, Eric Hahnen, Christopher A Haiman, Christopher R Hake, Per Hall, Ute
Hamann, Elaine F Harkness, Bernadette A M Heemskerk-Gerritsen, Peter Hillemanns, Frans B L
Hogervorst, Bernd Holleczek, Antoinette Hollestelle, Maartje J Hooning, Robert N Hoover, John L
Hopper, Anthony Howell, Hanna Huebner, Peter J Hulick, Evgeny N Imyanitov, , , Claudine Isaacs,
Louise Izatt, Agnes Jager, Milena Jakimovska, Anna Jakubowska, Paul James, Ramunas Janavicius,
Wolfgang Janni, Esther M John, Michael E Jones, Audrey Jung, Rudolf Kaaks, Pooja Middha Kapoor,
Beth Y Karlan, Renske Keeman, Sofia Khan, Elza Khusnutdinova, Cari M Kitahara, Yon-Dschun Ko,
Irene Konstantopoulou, Linetta B Koppert, Stella Koutros, Vessela N Kristensen, Anne-Vibeke
Laenkholm, Diether Lambrechts, Susanna C Larsson, Pierre Laurent-Puig, Conxi Lazaro, Emilija
Lazarova, Flavio Lejbkowicz, Goska Leslie, Fabienne Lesueur, Annika Lindblom, Jolanta
Lissowska, Wing-Yee Lo, Jennifer T Loud, Jan Lubinski, Alicja Lukomska, Robert J MacInnis, Arto
Mannermaa, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, Maria Elena Martinez,
Laura Matricardi, Lesley McGuffog, Catriona McLean, Noura Mebirouk, Alfons Meindl, Usha
Menon, Austin Miller, Elvira Mingazheva, Marco Montagna, Anna Marie Mulligan, Claire Mulot,
Taru A Muranen, Katherine L Nathanson, Susan L Neuhausen, Heli Nevanlinna, Patrick Neven,
William G Newman, Finn C Nielsen, Liene Nikitina-Zake, Jesse Nodora, Kenneth Offit, Edith Olah,
Olufunmilayo I Olopade, Håkan Olsson, Nick Orr, Laura Papi, Janos Papp, Tjoung-Won Park-
Simon, Michael T Parsons, Bernard Peissel, Ana Peixoto, Beth Peshkin, Paolo Peterlongo, Julian
Peto, Kelly-Anne Phillips, Marion Piedmonte, Dijana Plaseska-Karanfilska, Karolina Prajzendanc,
Ross Prentice, Darya Prokofyeva, Brigitte Rack, Paolo Radice, Susan J Ramus, Johanna Rantala,
Muhammad U Rashid, Gad Rennert, Hedy S Rennert, Harvey A Risch, Atocha Romero, Matti A
Rookus, Matthias Rübner, Thomas Rüdiger, Emmanouil Saloustros, Sarah Sampson, Dale P
Sandler, Elinor J Sawyer, Maren T Scheuner, Rita K Schmutzler, Andreas Schneeweiss, Minouk J
Schoemaker, Ben Schöttker, Peter Schürmann, Leigha Senter, Priyanka Sharma, Mark E
Sherman, Xiao-Ou Shu, Christian F Singer, Snezhana Smichkoska, Penny Soucy, Melissa C
Southey, John J Spinelli, Jennifer Stone, Dominique Stoppa-Lyonnet, , , Anthony J Swerdlow, Csilla
I Szabo, Rulla M Tamimi, William J Tapper, Jack A Taylor, Manuel R Teixeira, MaryBeth Terry,
Mads Thomassen, Darcy L Thull, Marc Tischkowitz, Amanda E Toland, Rob A E M Tollenaar, Ian
Tomlinson, Diana Torres, Melissa A Troester, Thérèse Truong, Nadine Tung, Michael Untch,
Celine M Vachon, Ans M W van den Ouweland, Lizet E van der Kolk, Elke M van Veen, Elizabeth J
vanRensburg, Ana Vega, Barbara Wappenschmidt, Clarice R Weinberg, Jeffrey N Weitzel, Hans
Wildiers, Robert Winqvist, Alicja Wolk, Xiaohong R Yang, Drakoulis Yannoukakos, Wei Zheng,
Kristin K Zorn, Roger L Milne, Peter Kraft, Jacques Simard, Paul D P Pharoah, Kyriaki Michailidou,
Antonis C Antoniou, Marjanka K Schmidt, Georgia Chenevix-Trench, Douglas F Easton, Nilanjan
Chatterjee, Montserrat García-Closas (2020 May 20)
Genome-wide association study identifies 32 novel breast cancer susceptibility
loci from overall and subtype-specific analyses.
Nature genetics : 572-581 : DOI : 10.1038/s41588-020-0609-2
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 9Publications de l’équipe
Épidémiologie génétique des cancers
Résumé
Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor
subtype. To identify novel loci, we performed a genome-wide association study including
133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers
(9,414 with breast cancer) of European ancestry, using both standard and novel
methodologies that account for underlying tumor heterogeneity by estrogen receptor,
progesterone receptor and human epidermal growth factor receptor 2 status and tumor
grade. We identified 32 novel susceptibility loci (P < 5.0 × 10), 15 of which showed evidence
for associations with at least one tumor feature (false discovery rate < 0.05). Five loci
showed associations (P < 0.05) in opposite directions between luminal and non-luminal
subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that
differed between normal luminal and basal mammary cells. The genetic correlations between
five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip
heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease
and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which
included 330 variants, for the highest 1% of quantiles compared with middle quantiles were
5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings
provide an improved understanding of genetic predisposition to breast cancer subtypes and
will inform the development of subtype-specific polygenic risk scores.
Helian Feng, Alexander Gusev, Bogdan Pasaniuc, Lang Wu, Jirong Long, Zomoroda Abu-Full,
Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Adalgeir Arason,
Volker Arndt, Kristan J Aronson, Banu K Arun, Ella Asseryanis, Paul L Auer, Jacopo Azzollini, Judith
Balmaña, Rosa B Barkardottir, Daniel R Barnes, Daniel Barrowdale, Matthias W Beckmann,
Sabine Behrens, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska, Ana Blanco, Carl
Blomqvist, Bram Boeckx, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Bernardo
Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Annegien Broeks, Thomas
Brüning, Barbara Burwinkel, Qiuyin Cai, Trinidad Caldés, Maria A Caligo, Ian Campbell, Sander
Canisius, Daniele Campa, Brian D Carter, Jonathan Carter, Jose E Castelao, Jenny Chang-Claude,
Stephen J Chanock, Hans Christiansen, Wendy K Chung, Kathleen B M Claes, Christine L Clarke, ,
, , Fergus J Couch, Angela Cox, Simon S Cross, Cezary Cybulski, Kamila Czene, Mary B Daly,
Miguel de la Hoya, Kim De Leeneer, Joe Dennis, Peter Devilee, Orland Diez, Susan M Domchek,
Thilo Dörk, Isabel Dos-Santos-Silva, Alison M Dunning, Miriam Dwek, Diana M Eccles, Bent
Ejlertsen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, Peter A Fasching, Olivia Fletcher,
Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Marike Gabrielson,
Patricia A Ganz, Susan M Gapstur, Judy Garber, Montserrat García-Closas, José A García-Sáenz,
Mia M Gaudet, Graham G Giles, Gord Glendon, Andrew K Godwin, Mark S Goldberg, David E
Goldgar, Anna González-Neira, Mark H Greene, Jacek Gronwald, Pascal Guénel, Christopher A
Haiman, Per Hall, Ute Hamann, Christopher Hake, Wei He, Jane Heyworth, Frans B L Hogervorst,
Antoinette Hollestelle, Maartje J Hooning, Robert N Hoover, John L Hopper, Guanmengqian
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 10Publications de l’équipe
Épidémiologie génétique des cancers
Huang, Peter J Hulick, Keith Humphreys, Evgeny N Imyanitov, , , , , Claudine Isaacs, Milena
Jakimovska, Anna Jakubowska, Paul James, Ramunas Janavicius, Rachel C Jankowitz, Esther M
John, Nichola Johnson, Vijai Joseph, Audrey Jung, Beth Y Karlan, Elza Khusnutdinova, Johanna I
Kiiski, Irene Konstantopoulou, Vessela N Kristensen, Yael Laitman, Diether Lambrechts, Conxi
Lazaro, Dominique Leroux, Goska Leslie, Jenny Lester, Fabienne Lesueur, Noralane Lindor, Sara
Lindström, Wing-Yee Lo, Jennifer T Loud, Jan Lubiński, Enes Makalic, Arto Mannermaa, Mehdi
Manoochehri, Siranoush Manoukian, Sara Margolin, John W M Martens, Maria E Martinez, Laura
Matricardi, Tabea Maurer, Dimitrios Mavroudis, Lesley McGuffog, Alfons Meindl, Usha Menon,
Kyriaki Michailidou, Pooja M Kapoor, Austin Miller, Marco Montagna, Fernando Moreno, Lidia
Moserle, Anna M Mulligan, Taru A Muranen, Katherine L Nathanson, Susan L Neuhausen, Heli
Nevanlinna, Ines Nevelsteen, Finn C Nielsen, Liene Nikitina-Zake, Kenneth Offit, Edith Olah,
Olufunmilayo I Olopade, Håkan Olsson, Ana Osorio, Janos Papp, Tjoung-Won Park-Simon, Michael
T Parsons, Inge S Pedersen, Ana Peixoto, Paolo Peterlongo, Julian Peto, Paul D P Pharoah, Kelly-
Anne Phillips, Dijana Plaseska-Karanfilska, Bruce Poppe, Nisha Pradhan, Karolina Prajzendanc,
Nadege Presneau, Kevin Punie, Katri Pylkäs, Paolo Radice, Johanna Rantala, Muhammad Usman
Rashid, Gad Rennert, Harvey A Risch, Mark Robson, Atocha Romero, Emmanouil Saloustros, Dale
P Sandler, Catarina Santos, Elinor J Sawyer, Marjanka K Schmidt, Daniel F Schmidt, Rita K
Schmutzler, Minouk J Schoemaker, Rodney J Scott, Priyanka Sharma, Xiao-Ou Shu, Jacques
Simard, Christian F Singer, Anne-Bine Skytte, Penny Soucy, Melissa C Southey, John J Spinelli,
Amanda B Spurdle, Jennifer Stone, Anthony J Swerdlow, William J Tapper, Jack A Taylor, Manuel R
Teixeira, Mary Beth Terry, Alex Teulé, Mads Thomassen, Kathrin Thöne, Darcy L Thull, Marc
Tischkowitz, Amanda E Toland, Rob A E M Tollenaar, Diana Torres, Thérèse Truong, Nadine Tung,
Celine M Vachon, Christi J van Asperen, Ans M W van den Ouweland, Elizabeth J van Rensburg,
Ana Vega, Alessandra Viel, Paula Vieiro-Balo, Qin Wang, Barbara Wappenschmidt, Clarice R
Weinberg, Jeffrey N Weitzel, Camilla Wendt, Robert Winqvist, Xiaohong R Yang, Drakoulis
Yannoukakos, Argyrios Ziogas, Roger L Milne, Douglas F Easton, Georgia Chenevix-Trench, Wei
Zheng, Peter Kraft, Xia Jiang (2020 Mar 3)
Transcriptome-wide association study of breast cancer risk by estrogen-
receptor status.
Genetic epidemiology : 442-468 : DOI : 10.1002/gepi.22288
Résumé
Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk
genes by integrating data from expression quantitative loci and genome-wide association
studies (GWAS), but analyses of breast cancer subtype-specific associations have been
limited. In this study, we conducted a TWAS using gene expression data from GTEx and
summary statistics from the hitherto largest GWAS meta-analysis conducted for breast
cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared
associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also
conducted multigene conditional analyses in regions with multiple TWAS associations. Two
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 11Publications de l’équipe
Épidémiologie génétique des cancers
genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER-
breast cancer. We further identified 30 TWAS-significant genes associated with overall breast
cancer risk, including four that were not identified in previous studies. Conditional analyses
identified single independent breast-cancer gene in three of six regions harboring multiple
TWAS-significant genes. Our study provides new information on breast cancer genetics and
biology, particularly about genomic differences between ER+ and ER- breast cancer.
Gisella Figlioli, Anders Kvist, Emma Tham, Jana Soukupova, Petra Kleiblova, Taru A Muranen,
Nadine Andrieu, Jacopo Azzollini, Judith Balmaña, Alicia Barroso, Javier Benítez, Birgitte
Bertelsen, Ana Blanco, Bernardo Bonanni, Åke Borg, Joan Brunet, Daniele Calistri, Mariarosaria
Calvello, Stepan Chvojka, Laura Cortesi, Esther Darder, Jesús Del Valle, Orland Diez, , Séverine
Eon-Marchais, Florentia Fostira, , Francesca Gensini, Claude Houdayer, Marketa Janatova,
Johanna I Kiiski, Irene Konstantopoulou, Katerina Kubelka-Sabit, Conxi Lázaro, Fabienne Lesueur,
Siranoush Manoukian, Ruta Marcinkute, Ugnius Mickys, Virginie Moncoutier, , Aleksander Myszka,
Tu Nguyen-Dumont, Finn Cilius Nielsen, Rimvydas Norvilas, Edith Olah, Ana Osorio, Laura Papi,
Bernard Peissel, Ana Peixoto, Dijana Plaseska-Karanfilska, Timea Pócza, Maria Rossing, Vilius
Rudaitis, Marta Santamariña, Catarina Santos, Snezhana Smichkoska, Melissa C Southey,
Dominique Stoppa-Lyonnet, Manuel Teixeira, Therese Törngren, Angela Toss, Miguel Urioste, Ana
Vega, Zdenka Vlckova, Drakoulis Yannoukakos, Valentina Zampiga, Zdenek Kleibl, Paolo Radice,
Heli Nevanlinna, Hans Ehrencrona, Ramunas Janavicius, Paolo Peterlongo (2020 Jan 30)
The Spectrum of Protein Truncating Variants in European Breast Cancer Cases.
Cancers : DOI : E292
Résumé
Germline protein truncating variants (PTVs) in the gene have been associated with a 2-4-fold
increased breast cancer risk in case-control studies conducted in different European
populations. However, the distribution and the frequency of PTVs in Europe have never been
investigated. In the present study, we collected the data of 114 European female breast
cancer cases with PTVs ascertained in 20 centers from 13 European countries. We identified
27 different PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a
maximum frequency in Finland and a lower relative frequency in Southern Europe. On the
contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also
showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and
p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique PTVs,
15 have not been previously reported. We provide here the initial spectrum of PTVs in
European breast cancer cases.
Nasim Mavaddat, Antonis C Antoniou, Thea M Mooij, Maartje J Hooning, Bernadette A
Heemskerk-Gerritsen, , Catherine Noguès, Marion Gauthier-Villars, Olivier Caron, Paul Gesta,
Pascal Pujol, Alain Lortholary, , Daniel Barrowdale, Debra Frost, D Gareth Evans, Louise Izatt,
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 12Publications de l’équipe
Épidémiologie génétique des cancers
Julian Adlard, Ros Eeles, Carole Brewer, Marc Tischkowitz, Alex Henderson, Jackie Cook, Diana
Eccles, , Klaartje van Engelen, Marian J E Mourits, Margreet G E M Ausems, Linetta B Koppert,
John L Hopper, Esther M John, Wendy K Chung, Irene L Andrulis, Mary B Daly, Saundra S Buys, ,
Javier Benitez, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F Singer, Yen Tan,
Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-José Roos-Blom, Flora E
Van Leeuwen, Brita Arver, Håkan Olsson, Rita K Schmutzler, Christoph Engel, Karin Kast, Kelly-
Anne Phillips, Mary Beth Terry, Roger L Milne, David E Goldgar, Matti A Rookus, Nadine Andrieu,
Douglas F Easton, , , (2020 Jan 18)
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer
risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.
Breast cancer research : BCR : 8 : DOI : 10.1186/s13058-020-1247-4
Résumé
The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1
and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a
protective effect but may be substantially biased. Prospective studies have had limited
power, particularly for BRCA2 mutation carriers. Further, previous studies have not
considered the effect of RRSO in the context of natural menopause.
Laura Fachal, Hugues Aschard, Jonathan Beesley, Daniel R Barnes, Jamie Allen, Siddhartha Kar,
Karen A Pooley, Joe Dennis, Kyriaki Michailidou, Constance Turman, Penny Soucy, Audrey
Lemaçon, Michael Lush, Jonathan P Tyrer, Maya Ghoussaini, Mahdi Moradi Marjaneh, Xia Jiang,
Simona Agata, Kristiina Aittomäki, M Rosario Alonso, Irene L Andrulis, Hoda Anton-Culver, Natalia
N Antonenkova, Adalgeir Arason, Volker Arndt, Kristan J Aronson, Banu K Arun, Bernd Auber, Paul
L Auer, Jacopo Azzollini, Judith Balmaña, Rosa B Barkardottir, Daniel Barrowdale, Alicia Beeghly-
Fadiel, Javier Benitez, Marina Bermisheva, Katarzyna Białkowska, Amie M Blanco, Carl Blomqvist,
William Blot, Natalia V Bogdanova, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Ake Borg,
Kristin Bosse, Hiltrud Brauch, Hermann Brenner, Ignacio Briceno, Ian W Brock, Angela Brooks-
Wilson, Thomas Brüning, Barbara Burwinkel, Saundra S Buys, Qiuyin Cai, Trinidad Caldés, Maria
A Caligo, Nicola J Camp, Ian Campbell, Federico Canzian, Jason S Carroll, Brian D Carter, Jose E
Castelao, Jocelyne Chiquette, Hans Christiansen, Wendy K Chung, Kathleen B M Claes, Christine
L Clarke, , , J Margriet Collée, Sten Cornelissen, Fergus J Couch, Angela Cox, Simon S Cross,
Cezary Cybulski, Kamila Czene, Mary B Daly, Miguel de la Hoya, Peter Devilee, Orland Diez, Yuan
Chun Ding, Gillian S Dite, Susan M Domchek, Thilo Dörk, Isabel Dos-Santos-Silva, Arnaud Droit,
Stéphane Dubois, Martine Dumont, Mercedes Duran, Lorraine Durcan, Miriam Dwek, Diana M
Eccles, Christoph Engel, Mikael Eriksson, D Gareth Evans, Peter A Fasching, Olivia Fletcher,
Giuseppe Floris, Henrik Flyger, Lenka Foretova, William D Foulkes, Eitan Friedman, Lin Fritschi,
Debra Frost, Marike Gabrielson, Manuela Gago-Dominguez, Gaetana Gambino, Patricia A Ganz,
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 13Publications de l’équipe
Épidémiologie génétique des cancers
Susan M Gapstur, Judy Garber, José A García-Sáenz, Mia M Gaudet, Vassilios Georgoulias,
Graham G Giles, Gord Glendon, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Anna
González-Neira, Maria Grazia Tibiletti, Mark H Greene, Mervi Grip, Jacek Gronwald, Anne Grundy,
Pascal Guénel, Eric Hahnen, Christopher A Haiman, Niclas Håkansson, Per Hall, Ute Hamann,
Patricia A Harrington, Jaana M Hartikainen, Mikael Hartman, Wei He, Catherine S Healey,
Bernadette A M Heemskerk-Gerritsen, Jane Heyworth, Peter Hillemanns, Frans B L Hogervorst,
Antoinette Hollestelle, Maartje J Hooning, John L Hopper, Anthony Howell, Guanmengqian Huang,
Peter J Hulick, Evgeny N Imyanitov, , , , Claudine Isaacs, Motoki Iwasaki, Agnes Jager, Milena
Jakimovska, Anna Jakubowska, Paul A James, Ramunas Janavicius, Rachel C Jankowitz, Esther M
John, Nichola Johnson, Michael E Jones, Arja Jukkola-Vuorinen, Audrey Jung, Rudolf Kaaks,
Daehee Kang, Pooja Middha Kapoor, Beth Y Karlan, Renske Keeman, Michael J Kerin, Elza
Khusnutdinova, Johanna I Kiiski, Judy Kirk, Cari M Kitahara, Yon-Dschun Ko, Irene
Konstantopoulou, Veli-Matti Kosma, Stella Koutros, Katerina Kubelka-Sabit, Ava Kwong, Kyriacos
Kyriacou, Yael Laitman, Diether Lambrechts, Eunjung Lee, Goska Leslie, Jenny Lester, Fabienne
Lesueur, Annika Lindblom, Wing-Yee Lo, Jirong Long, Artitaya Lophatananon, Jennifer T Loud, Jan
Lubiński, Robert J MacInnis, Tom Maishman, Enes Makalic, Arto Mannermaa, Mehdi Manoochehri,
Siranoush Manoukian, Sara Margolin, Maria Elena Martinez, Keitaro Matsuo, Tabea Maurer,
Dimitrios Mavroudis, Rebecca Mayes, Lesley McGuffog, Catriona McLean, Noura Mebirouk, Alfons
Meindl, Austin Miller, Nicola Miller, Marco Montagna, Fernando Moreno, Kenneth Muir, Anna Marie
Mulligan, Victor M Muñoz-Garzon, Taru A Muranen, Steven A Narod, Rami Nassir, Katherine L
Nathanson, Susan L Neuhausen, Heli Nevanlinna, Patrick Neven, Finn C Nielsen, Liene Nikitina-
Zake, Aaron Norman, Kenneth Offit, Edith Olah, Olufunmilayo I Olopade, Håkan Olsson, Nick Orr,
Ana Osorio, V Shane Pankratz, Janos Papp, Sue K Park, Tjoung-Won Park-Simon, Michael T
Parsons, James Paul, Inge Sokilde Pedersen, Bernard Peissel, Beth Peshkin, Paolo Peterlongo,
Julian Peto, Dijana Plaseska-Karanfilska, Karolina Prajzendanc, Ross Prentice, Nadege Presneau,
Darya Prokofyeva, Miquel Angel Pujana, Katri Pylkäs, Paolo Radice, Susan J Ramus, Johanna
Rantala, Rohini Rau-Murthy, Gad Rennert, Harvey A Risch, Mark Robson, Atocha Romero, Maria
Rossing, Emmanouil Saloustros, Estela Sánchez-Herrero, Dale P Sandler, Marta Santamariña,
Christobel Saunders, Elinor J Sawyer, Maren T Scheuner, Daniel F Schmidt, Rita K Schmutzler,
Andreas Schneeweiss, Minouk J Schoemaker, Ben Schöttker, Peter Schürmann, Christopher
Scott, Rodney J Scott, Leigha Senter, Caroline M Seynaeve, Mitul Shah, Priyanka Sharma, Chen-
Yang Shen, Xiao-Ou Shu, Christian F Singer, Thomas P Slavin, Snezhana Smichkoska, Melissa C
Southey, John J Spinelli, Amanda B Spurdle, Jennifer Stone, Dominique Stoppa-Lyonnet, Christian
Sutter, Anthony J Swerdlow, Rulla M Tamimi, Yen Yen Tan, William J Tapper, Jack A Taylor,
Manuel R Teixeira, Maria Tengström, Soo Hwang Teo, Mary Beth Terry, Alex Teulé, Mads
Thomassen, Darcy L Thull, Marc Tischkowitz, Amanda E Toland, Rob A E M Tollenaar, Ian
Tomlinson, Diana Torres, Gabriela Torres-Mejía, Melissa A Troester, Thérèse Truong, Nadine
Tung, Maria Tzardi, Hans-Ulrich Ulmer, Celine M Vachon, Christi J van Asperen, Lizet E van der
Kolk, Elizabeth J van Rensburg, Ana Vega, Alessandra Viel, Joseph Vijai, Maartje J Vogel, Qin
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 14Publications de l’équipe
Épidémiologie génétique des cancers
Wang, Barbara Wappenschmidt, Clarice R Weinberg, Jeffrey N Weitzel, Camilla Wendt, Hans
Wildiers, Robert Winqvist, Alicja Wolk, Anna H Wu, Drakoulis Yannoukakos, Yan Zhang, Wei
Zheng, David Hunter, Paul D P Pharoah, Jenny Chang-Claude, Montserrat García-Closas,
Marjanka K Schmidt, Roger L Milne, Vessela N Kristensen, Juliet D French, Stacey L Edwards,
Antonis C Antoniou, Georgia Chenevix-Trench, Jacques Simard, Douglas F Easton, Peter Kraft,
Alison M Dunning (2020 Jan 9)
Fine-mapping of 150 breast cancer risk regions identifies 191 likely target
genes.
Nature genetics : 56-73 : DOI : 10.1038/s41588-019-0537-1
Résumé
Genome-wide association studies have identified breast cancer risk variants in over 150
genomic regions, but the mechanisms underlying risk remain largely unknown. These
regions were explored by combining association analysis with in silico genomic feature
annotations. We defined 205 independent risk-associated signals with the set of credible
causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that
combines genetic association, linkage disequilibrium and enriched genomic features to
determine variants with high posterior probabilities of being causal. Potentially causal
variants were significantly over-represented in active gene regulatory regions and
transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as
targets of those potentially causal variants, using gene expression (expression quantitative
trait loci), chromatin interaction and functional annotations. Known cancer drivers,
transcription factors and genes in the developmental, apoptosis, immune system and DNA
integrity checkpoint gene ontology pathways were over-represented among the highest-
confidence target genes.
Année de publication : 2019
Xin Yang, Goska Leslie, Alicja Doroszuk, Sandra Schneider, Jamie Allen, Brennan Decker, Alison M
Dunning, James Redman, James Scarth, Inga Plaskocinska, Craig Luccarini, Mitul Shah, Karen
Pooley, Leila Dorling, Andrew Lee, Muriel A Adank, Julian Adlard, Kristiina Aittomäki, Irene L
Andrulis, Peter Ang, Julian Barwell, Jonine L Bernstein, Kristie Bobolis, Åke Borg, Carl Blomqvist,
Kathleen B M Claes, Patrick Concannon, Adeline Cuggia, Julie O Culver, Francesca Damiola,
Antoine de Pauw, Orland Diez, Jill S Dolinsky, Susan M Domchek, Christoph Engel, D Gareth
Evans, Florentia Fostira, Judy Garber, Lisa Golmard, Ellen L Goode, Stephen B Gruber, Eric
Hahnen, Christopher Hake, Tuomas Heikkinen, Judith E Hurley, Ramunas Janavicius, Zdenek
Kleibl, Petra Kleiblova, Irene Konstantopoulou, Anders Kvist, Holly Laduca, Ann S G Lee, Fabienne
Lesueur, Eamonn R Maher, Arto Mannermaa, Siranoush Manoukian, Rachel McFarland, Wendy
McKinnon, Alfons Meindl, Kelly Metcalfe, Nur Aishah Mohd Taib, Jukka Moilanen, Katherine L
Nathanson, Susan Neuhausen, Pei Sze Ng, Tu Nguyen-Dumont, Sarah M Nielsen, Florian
Obermair, Kenneth Offit, Olufunmilayo I Olopade, Laura Ottini, Judith Penkert, Katri Pylkäs, Paolo
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 15Publications de l’équipe
Épidémiologie génétique des cancers
Radice, Susan J Ramus, Vilius Rudaitis, Lucy Side, Rachel Silva-Smith, Valentina Silvestri, Anne-
Bine Skytte, Thomas Slavin, Jana Soukupova, Carlo Tondini, Alison H Trainer, Gary Unzeitig, Lydia
Usha, Thomas van Overeem Hansen, James Whitworth, Marie Wood, Cheng Har Yip, Sook-Yee
Yoon, Amal Yussuf, George Zogopoulos, David Goldgar, John L Hopper, Georgia Chenevix-Trench,
Paul Pharoah, Sophia H L George, Judith Balmaña, Claude Houdayer, Paul James, Zaki El-Haffaf,
Hans Ehrencrona, Marketa Janatova, Paolo Peterlongo, Heli Nevanlinna, Rita Schmutzler, Soo-
Hwang Teo, Mark Robson, Tuya Pal, Fergus Couch, Jeffrey N Weitzel, Aaron Elliott, Melissa
Southey, Robert Winqvist, Douglas F Easton, William D Foulkes, Antonis C Antoniou, Marc
Tischkowitz (2019 Dec 17)
Cancer Risks Associated With Germline Pathogenic Variants: An International
Study of 524 Families.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology :
674-685 : DOI : 10.1200/JCO.19.01907
Résumé
To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate
risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with
germline pathogenic variants (PVs) because these risks have not been extensively
characterized.
INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 16You can also read
