Citations 2
Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
Morra, Anna , Andrulis, Irene L. , Beckmann, Matthias W. , Bolla, Manjeet K. , Camp, Nicola J. , Cessna, Melissa H., Chang‐Claude, Jenny , Collaborators, NBCS, Daly, Mary B., Easton, Douglas F. , Eccles, Diana M., Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Gündert, Melanie , Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harrington, Patricia, Hoppe, Reiner , Howell, Anthony , Investigators, ABCTB, Investigators, kConFab, Janni, Wolfgang, Johnson, Nichola , Kristensen, Vessela N. , Lindblom, Annika , Mannermaa, Arto , Mavroudis, Dimitrios, Nevelsteen, Ines, Neven, Patrick , Obi, Nadia , Offit, Kenneth , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Phillips, Kelly‐Anne , Plaseska-Karanfilska, Dijana, Rack, Brigitte , Rhenius, Valerie , Sawyer, Elinor J. , Schmutzler, Rita K. , Schuetze, Sabine, Shah, Mitul , Smichkoska, Snezhana , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Vachon, Celine M. , Veen, Elke M. van , Wang, Qin , Wendt, Camilla, Wildiers, Hans , Adank, Muriel A. , Hooning, Maartje J. , Eccles, Diana , Plaseska‐Karanfilska, Dijana , Eccles, Diana , Evans, D Gareth , García-Closas, Montserrat , Phillips, Kelly-Anne , Wildiers, Hans , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Schreurs, Maartje A. C. , Anton‐Culver, Hoda , Augustinsson, Annelie , Behrens, Sabine , Bojesen, Stig E. , Brauch, Hiltrud , Broeks, Annegien , Buys, Saundra S. , Castelao, Jose E. , Chung, Wendy K. , Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Dennis, Joe , Devilee, Peter , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , Eriksson, Mikael , Fehm, Tanja , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Graßmann, Felix , Hartikainen, Jaana M. , Hopper, John L. , Houlston, Richard S. , Jakubowska, Anna , Jernström, Helena , John, Esther M. , Jones, Michael E. , Kurian, Allison W. , Lambrechts, Diether , Marchand, Loı̈c Le , Lubiński, Jan , Lux, Michael P. , Mulligan, Anna Marie , Muranen, Taru , Nevanlinna, Heli , Newman, William G. , Olshan, Andrew F. , Peterlongo, Paolo , Polley, Eric C. , Presneau, Nadège , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Robson, Mark E. , Romero, Atocha , Saloustros, Emmanouil , Scott, Christopher, Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Tomczyk, Katarzyna , Troester, Melissa A. , Vachon, Celine M. , Winqvist, Robert , Ziogas, Argyrios , Hall, Per N , Pharoah, Paul D.P. , Hollestelle, Antoinette , Schmidt, Marjanka K.
No container title available | February 13, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09–1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words)
Rare Copy Number Variants (CNVs) and Breast Cancer Risk
Dorling, Leila , Bola, Manjeet, Wang, Qin , Andrulis, Irene L. , Antonenkova, Natalia, Aronson, Kristan J. , Freeman, Laura Beane, Beckmann, Matthias W. , Bojeson, Stig, Chang‐Claude, Jenny , Chenevix‐Trench, Georgia , Collaborators, NBCS, Collée, J. Margriet, Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, Hahen, Eric, Haiman, Christopher A. , Hoppe, Reine, Investigators, ACTB, Investigators, kConFab, Jager, Agnes , Johnson, Nichola , Keeman, Renske , Ko, Yon‐Dschun, Kosma, Veli‐Matti , Kristensen, Vessela N. , Kubelka‐Sabit, Katerina , Kurian, Alison, Larson, Nicole L. , Linet, Martha S. , Łukomska, Alicja, Mannermaa, Arto , Mavroudis, Dimitrios, Park‐Simon, Tjoung‐Won , Peterlongo, Paolo , Plaseska-Karanfilska, Dijana, Sawyer, Elinor J. , Schmutzler, Rita K., Shibli, Rana , Soucy, Penny, Tomlinson, Ian , Vachon, Celine M. , Wendt, Camilla, Yang, Xiaohong R. , Easton, Douglas F. , Peterlongo, Paolo , Evans, D Gareth , Chenevix-Trench, Georgia , Sawyer, Elinor J , Dennis, Joe , Tyrer, Jonathan P. , Walker, Logan C. , Michailidou, Kyriaki , Ahearn, Thomas U. , Anton‐Culver, Hoda , Arndt, Volker , Behrens, Sabine , Benı́tez, Javier , Bermisheva, Marina , Bojesen, Stig E. , Brenner, Hermann , Castelao, Jose E. , Clarke, Christine L. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Devilee, Peter , Dörk, Thilo , Dossus, Laure , Eliassen, A. Heather , Eriksson, Mikael , Figueroa, Jonine D. , Fletcher, Olivia , Fritschi, Lin , Gabrielson, Marike , Gago-Domínguez, Manuela , García‐Closas, Montserrat , Giles, Graham G. , González‐Neira, Anna , Guénel, Pascal , Hall, Per N , Hollestelle, Antoinette , Hoppe, Reiner , Hopper, John L. , Howell, Anthony , Jakubowska, Anna , John, Esther M. , Jones, Michael E. , Jung, Audrey , Kaaks, Rudolf , Хуснутдинова, Э. К. , Kitahara, Cari M. , Koutros, Stella , Kraft, Peter , Lambrechts, Diether , Manoukian, Siranoush , Margolin, Sara , Milne, Roger L. , Muranen, Taru , Murphy, Rachel A. , Nevanlinna, Heli , Olson, Janet E. , Olsson, Håkan , Perou, Charles M. , Pylkäs, Katri , Rennert, Gad , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Smeets, Ann , Southey, Melissa C. , Swerdlow, Anthony J. , Tamimi, Rulla M. , Taylor, Jack A. , Teras, Lauren R. , Terry, Mary Beth , Troester, Melissa A. , Truong, Thérèse , Vachon, Celine M. , Wendt, Camilla, Winqvist, Robert , Wolk, Alicja , Zheng, Wei , Ziogas, Argyrios , Simard, Jacques , Dunning, Alison M. , Pharoah, Paul D.P.
No container title available | June 22, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.