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Your search keyword '"Arndt, Volker [0000-0001-9320-8684]"' showing total 9 results
Start Over Author "Arndt, Volker [0000-0001-9320-8684]" Topic risk factors
9 results on '"Arndt, Volker [0000-0001-9320-8684]"'

1. Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies

Author

Jung, Audrey Y, Ahearn, Thomas U, Behrens, Sabine, Middha, Pooja, Bolla, Manjeet K, Wang, Qin, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Beane Freeman, Laura E, Becher, Heiko, Brenner, Hermann, Canzian, Federico, Carey, Lisa A, CTS Consortium, Czene, Kamila, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Figueroa, Jonine D, Fritschi, Lin, Gabrielson, Marike, Giles, Graham G, Guénel, Pascal, Hadjisavvas, Andreas, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hoppe, Reiner, Hopper, John L, Howell, Anthony, Hunter, David J, Hüsing, Anika, Kaaks, Rudolf, Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Lacey, James V, Le Marchand, Loic, Lissowska, Jolanta, Loizidou, Maria A, Mannermaa, Arto, Maurer, Tabea, Murphy, Rachel A, Olshan, Andrew F, Olsson, Håkan, Patel, Alpa V, Perou, Charles M, Rennert, Gad, Shibli, Rana, Shu, Xiao-Ou, Southey, Melissa C, Stone, Jennifer, Tamimi, Rulla M, Teras, Lauren R, Troester, Melissa A, Truong, Thérèse, Vachon, Celine M, Wang, Sophia S, Wolk, Alicja, Wu, Anna H, Yang, Xiaohong R, Zheng, Wei, Dunning, Alison M, Pharoah, Paul DP, Easton, Douglas F, Milne, Roger L, Chatterjee, Nilanjan, Schmidt, Marjanka K, García-Closas, Montserrat, Chang-Claude, Jenny, Jung, Audrey Y [0000-0003-0875-6673], Ahearn, Thomas U [0000-0003-0771-7752], Behrens, Sabine [0000-0002-9714-104X], Middha, Pooja [0000-0001-5503-8215], Wang, Qin [0000-0002-9139-0627], Arndt, Volker [0000-0001-9320-8684], Aronson, Kristan J [0000-0002-7865-7243], Becher, Heiko [0000-0002-8808-6667], Brenner, Hermann [0000-0002-6129-1572], Canzian, Federico [0000-0002-4261-4583], Czene, Kamila [0000-0002-3233-5695], Eliassen, A Heather [0000-0002-3961-6609], Figueroa, Jonine D [0000-0002-5100-623X], Fritschi, Lin [0000-0002-7692-3560], Gabrielson, Marike [0000-0002-3171-1556], Giles, Graham G [0000-0003-4946-9099], Guénel, Pascal [0000-0002-8359-518X], Hadjisavvas, Andreas [0000-0002-5636-0799], Håkansson, Niclas [0000-0001-7673-5554], Hall, Per [0000-0002-5640-9126], Hüsing, Anika [0000-0002-2685-9732], Koutros, Stella [0000-0001-5294-5485], Kraft, Peter [0000-0002-4472-8103], Le Marchand, Loic [0000-0001-5013-980X], Lissowska, Jolanta [0000-0003-2695-5799], Loizidou, Maria A [0000-0003-4503-7758], Mannermaa, Arto [0000-0001-8250-1930], Murphy, Rachel A [0000-0003-4383-5641], Olsson, Håkan [0000-0002-7721-4619], Patel, Alpa V [0000-0001-8834-9896], Perou, Charles M [0000-0001-9827-2247], Shu, Xiao-Ou [0000-0002-0711-8314], Southey, Melissa C [0000-0002-6313-9005], Stone, Jennifer [0000-0001-5077-0124], Tamimi, Rulla M [0000-0003-2306-8668], Vachon, Celine M [0000-0002-1962-9322], Wolk, Alicja [0000-0001-7387-6845], Dunning, Alison M [0000-0001-6651-7166], Pharoah, Paul DP [0000-0001-8494-732X], Easton, Douglas F [0000-0003-2444-3247], Milne, Roger L [0000-0001-5764-7268], Schmidt, Marjanka K [0000-0002-2228-429X], García-Closas, Montserrat [0000-0003-1033-2650], Chang-Claude, Jenny [0000-0001-8919-1971], and Apollo - University of Cambridge Repository

Subjects
Receptors, Estrogen, Receptor, ErbB-2, Risk Factors, Case-Control Studies, Biomarkers, Tumor, Humans, Female, Breast Neoplasms, Triple Negative Breast Neoplasms, Receptors, Progesterone
Abstract

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like. CONCLUSIONS: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

Published
2022

2. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Author

Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel C. Posner, Katja Mosconi, Cassianne Robinson-Cohen, Amy M. Mason, Thomas R. Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R. Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth L.M. Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustín Gómez de la Cámara, Vilmundur Gudnason, Graeme J. Hankey, Per-Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K. Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Koenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, Charlotte Onland-Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Tong, Rosario Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W.M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raul Zamora-Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nick Wareham, Elio Riboli, J.Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela M. Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Shaw, Robert Atkins, Paul Zimmet, Peter Whincup, Johann Willeit, Christoph Leitner, Anne Tybjaerg-Hansen, Peter Schnohr, Shoaib Afzal, David Lora Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, E. M. van Zutphen, N. M. van Schoor, Cinzia Lo Noce, Richard Kronmal, Georg Lappas, Peter M. Nilsson, Bo Hedblad, Jonathan Shaffer, Joseph Schwartz, Daichi Shimbo, Shinichi Sato, Mina Hayama-Terada, Simerjot Jassal, Thor Aspelund, Bolli Thorsson, Gunnar Sigurdsson, Layal Chaker, Kamran M. Ikram, Maryam Kavousi, Hugh Tunstall-Pedoe, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Edith Feskens, Johanna M Geleijnse, Daan Kromhout, Internal Medicine, Neurology, Epidemiology, Bell, Steven [0000-0001-6774-3149], Posner, Daniel C [0000-0002-3056-6924], Mason, Amy M [0000-0002-8019-0777], Allara, Elias [0000-0002-1634-8330], Staplin, Natalie [0000-0003-4482-4418], Arndt, Volker [0000-0001-9320-8684], Ärnlöv, Johan [0000-0002-6933-4637], Barr, Elizabeth LM [0000-0003-4284-1716], Boer, Jolanda MA [0000-0002-9714-4304], Brenner, Hermann [0000-0002-6129-1572], Casiglia, Edoardo [0000-0002-0003-3289], Chiodini, Paolo [0000-0003-0139-2264], Coresh, Josef [0000-0002-4598-0669], Cushman, Mary [0000-0002-7871-6143], Davidson, Karina W [0000-0002-9162-477X], de Jongh, Renate T [0000-0001-8414-3938], Engström, Gunnar [0000-0002-8618-9152], de la Cámara, Agustín Gómez [0000-0001-6827-6319], Gudnason, Vilmundur [0000-0001-5696-0084], Hankey, Graeme J [0000-0002-6044-7328], Hansson, Per-Olof [0000-0001-6323-0506], Heath, Alicia K [0000-0001-6517-1300], Hoorn, Ewout J [0000-0002-8738-3571], Imano, Hironori [0000-0002-6661-4254], Katzke, Verena [0000-0002-6509-6555], Kiechl, Stefan [0000-0002-9836-2514], Koenig, Wolfgang [0000-0002-2064-9603], Kronmal, Richard A [0000-0002-9897-7076], Kyrø, Cecilie [0000-0002-9083-8960], Ljungberg, Börje [0000-0002-4121-3753], MacDonald, Conor [0000-0002-4989-803X], Masala, Giovanna [0000-0002-5758-9069], Ninomiya, Toshiharu [0000-0003-1345-9032], Nordestgaard, Børge G [0000-0002-1954-7220], Onland-Moret, Charlotte [0000-0002-2360-913X], Palmieri, Luigi [0000-0002-4298-2642], Rosengren, Annika [0000-0002-5409-6605], Schulze, Matthias B [0000-0002-0830-5277], Sieri, Sabina [0000-0001-5201-172X], Sundström, Johan [0000-0003-2247-8454], Tikhonoff, Valérie [0000-0001-7846-0101], Tong, Tammy [0000-0002-0284-8959], Tzoulaki, Ioanna [0000-0002-4275-9328], van der Schouw, Yvonne T [0000-0002-4605-435X], Wannamethee, S Goya [0000-0001-9484-9977], Weiderpass, Elisabete [0000-0003-2237-0128], Willeit, Peter [0000-0002-1866-7159], Woodward, Mark [0000-0001-9800-5296], Yamagishi, Kazumasa [0000-0003-3301-5519], Zamora-Ros, Raul [0000-0002-6236-6804], Gagnon, David R [0000-0002-6367-3179], Tsao, Philip S [0000-0001-7274-9318], Edwards, Todd L [0000-0003-4318-6119], Damrauer, Scott M [0000-0001-8009-1632], Joseph, Jacob [0000-0002-7279-4896], Pennells, Lisa [0000-0002-8594-3061], Gaziano, Thomas A [0000-0002-5985-345X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nick [0000-0003-1422-2993], Hung, Adriana M [0000-0002-3203-1608], Butterworth, Adam S [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Gaziano, Liam, Sun, Luanluan, Arnold, Matthew, Bell, Steven, Cho, Kelly, Kaptoge, Stephen K, Song, Rebecca J, Burgess, Stephen, Posner, Daniel C, Mosconi, Katja, Robinson-Cohen, Cassianne, Mason, Amy M, Bolton, Thomas R, Tao, Ran, Allara, Elia, Schubert, Petra, Chen, Lingyan, Staley, James R, Staplin, Natalie, Altay, Servet, Amiano, Pilar, Arndt, Volker, Ärnlöv, Johan, Barr, Elizabeth L M, Björkelund, Cecilia, Boer, Jolanda M A, Brenner, Hermann, Casiglia, Edoardo, Chiodini, Paolo, Cooper, Jackie A, Coresh, Josef, Cushman, Mary, Dankner, Rachel, Davidson, Karina W, de Jongh, Renate T, Donfrancesco, Chiara, Engström, Gunnar, Freisling, Heinz, de la Cámara, Agustín Gómez, Gudnason, Vilmundur, Hankey, Graeme J, Hansson, Per-Olof, Heath, Alicia K, Hoorn, Ewout J, Imano, Hironori, Jassal, Simerjot K, Kaaks, Rudolf, Katzke, Verena, Kauhanen, Jussi, Kiechl, Stefan, Koenig, Wolfgang, Kronmal, Richard A, Kyrø, Cecilie, Lawlor, Deborah A, Ljungberg, Börje, Macdonald, Conor, Masala, Giovanna, Meisinger, Christa, Melander, Olle, Moreno Iribas, Conchi, Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Børge G, Onland-Moret, Charlotte, Palmieri, Luigi, Petrova, Dafina, Garcia, Jose Ramón Quiró, Rosengren, Annika, Sacerdote, Carlotta, Sakurai, Masaru, Santiuste, Carmen, Schulze, Matthias B, Sieri, Sabina, Sundström, Johan, Tikhonoff, Valérie, Tjønneland, Anne, Tong, Tammy, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Monique Verschuren, W M, Völzke, Henry, Wallace, Robert B, Wannamethee, S Goya, Weiderpass, Elisabete, Willeit, Peter, Woodward, Mark, Yamagishi, Kazumasa, Zamora-Ros, Raul, Akwo, Elvis A, Pyarajan, Saiju, Gagnon, David R, Tsao, Philip S, Muralidhar, Sumitra, Edwards, Todd L, Damrauer, Scott M, Joseph, Jacob, Pennells, Lisa, Wilson, Peter W F, Harrison, Seamu, Gaziano, Thomas A, Inouye, Michael, Baigent, Colin, Casas, Juan P, Langenberg, Claudia, Wareham, Nick, Riboli, Elio, Gaziano, J Michael, Danesh, John, Hung, Adriana M, Butterworth, Adam S, Wood, Angela M, Di Angelantonio, Emanuele, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology and Data Science, APH - Aging & Later Life, and APH - Personalized Medicine

Subjects
kidney disease, General Practice, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program, Coronary Disease, coronary disease, Kidney, Malalties coronàries, 1117 Public Health and Health Services, Coronary diseases, SDG 3 - Good Health and Well-being, cardiovascular disease, Risk Factors, Physiology (medical), Diabetes Mellitus, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Kardiologi, Kidney diseases, Malalties cardiovasculars, Cardiovascular Diseases, Kidney Diseases, Stroke, 1103 Clinical Sciences, Mendelian Randomization Analysis, kidney diseases, stroke, Allmänmedicin, Cardiovascular diseases, Cardiovascular System & Hematology, Malalties del ronyó, Cardiology and Cardiovascular Medicine, cardiovascular diseases
Abstract

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Published
2022

3. Rare germline copy number variants (CNVs) and breast cancer risk

Author

Easton, Douglas, Dennis, Joe [0000-0003-4591-1214], Tyrer, Jonathan P [0000-0003-3724-4757], Walker, Logan C [0000-0003-0018-3719], Michailidou, Kyriaki [0000-0001-7065-1237], Wang, Qin [0000-0002-9139-0627], Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Aronson, Kristan J [0000-0002-7865-7243], Behrens, Sabine [0000-0002-9714-104X], Dörk, Thilo [0000-0002-9458-0282], Dossus, Laure [0000-0003-2716-5748], Figueroa, Jonine [0000-0002-5100-623X], Fritschi, Lin [0000-0002-7692-3560], Giles, Graham G [0000-0003-4946-9099], Hollestelle, Antoinette [0000-0003-1166-1966], Jakubowska, Anna [0000-0002-5650-0501], Johnson, Nichola [0000-0002-8230-5662], Jones, Michael E [0000-0001-7479-3451], Keeman, Renske [0000-0002-5452-9933], Kristensen, Vessela N [0000-0001-5012-7438], Larson, Nicole L [0000-0002-2129-6934], Milne, Roger L [0000-0001-5764-7268], Nevanlinna, Heli [0000-0002-0916-2976], Olson, Janet E [0000-0003-4944-7789], Peterlongo, Paolo [0000-0001-6951-6855], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Rennert, Gad [0000-0002-8512-068X], Tomlinson, Ian [0000-0003-3037-1470], Truong, Thérèse [0000-0002-2943-6786], Vachon, Celine M [0000-0002-1962-9322], Wolk, Alicja [0000-0001-7387-6845], Ziogas, Argyrios [0000-0003-4529-3727], Simard, Jacques [0000-0001-6906-3390], Dunning, Alison M [0000-0001-6651-7166], Pharoah, Paul DP [0000-0001-8494-732X], Easton, Douglas F [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Germ Cells, DNA Copy Number Variations, Genome, Human, Risk Factors, Case-Control Studies, Humans, Breast Neoplasms, Female, Genome-Wide Association Study
Abstract

Funder: CIHR, Germline copy 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. Gene 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. To the best of our knowledge, this 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.

Published
2022
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4. Rare germline copy number variants (CNVs) and breast cancer risk

Author

Dennis, Joe, Tyrer, Jonathan, Walker, Logan C, Michailidou, Kyriaki, Dorling, Leila, Bolla, Manjeet K, Wang, Jean, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Freeman, Laura E Beane, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Brenner, Hermann, Castelao, Jose E, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Clarke, Christine L, Kristensen, Vessela N, Sahlberg, Kristine K, Børresen-Dale, Anne-Lise, Gram, Inger Torhild, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, Alnæs, Grethe I Grenaker, Collée, J Margriet, Lacey, James, Martinez, Elena, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Dossus, Laure, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Hall, Per, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L, Howell, Anthony, Clarke, Christine, Carpenter, Jane, Marsh, Deborah, Scott, Rodney, Baxter, Robert, Yip, Desmond, Davis, Alison, Pathmanathan, Nirmala, Simpson, Peter, Graham, Dinny, Sachchithananthan, Mythily, Campbell, Ian, De Fazio, Anna, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Milne, Roger, Southey, Melissa, Spurdle, Amanda, Thorne, Heather, Jager, Agnes, Jakubowska, Anna, John, Esther M, Johnson, Nichola, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Ko, Yon-Dschun, Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kubelka-Sabit, Katerina, Kurian, Allison W, Lacey, James V, Lambrechts, Diether, Larson, Nicole L, Linet, Martha, Ogrodniczak, Alicja, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L, Muranen, Taru A, Murphy, Rachel A, Nevanlinna, Heli, Olson, Janet E, Olsson, Håkan, Park-Simon, Tjoung-Won, Perou, Charles M, Peterlongo, Paolo, Plaseska-Karanfilska, Dijana, Pylkäs, Katri, Rennert, Gad, Saloustros, Emmanouil, Sandler, Dale P, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Shibli, Rana, Smeets, Ann, Soucy, Penny, Southey, Melissa C, Swerdlow, Anthony J, Tamimi, Rulla M, Taylor, Jack A, Teras, Lauren R, Terry, Mary Beth, Tomlinson, Ian, Troester, Melissa A, Truong, Thérèse, Vachon, Celine M, Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R, Zheng, Wei, Ziogas, Argyrios, Simard, Jacques, Dunning, Alison, Pharoah, Paul, Easton, Douglas, Dennis, Joe [0000-0003-4591-1214], Tyrer, Jonathan [0000-0003-3724-4757], Walker, Logan C [0000-0003-0018-3719], Michailidou, Kyriaki [0000-0001-7065-1237], Wang, Jean [0000-0002-9139-0627], Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Aronson, Kristan J [0000-0002-7865-7243], Behrens, Sabine [0000-0002-9714-104X], Kristensen, Vessela N [0000-0001-5012-7438], Dörk, Thilo [0000-0002-9458-0282], Dossus, Laure [0000-0003-2716-5748], Figueroa, Jonine [0000-0002-5100-623X], Fritschi, Lin [0000-0002-7692-3560], Giles, Graham G [0000-0003-4946-9099], Hollestelle, Antoinette [0000-0003-1166-1966], Jakubowska, Anna [0000-0002-5650-0501], Johnson, Nichola [0000-0002-8230-5662], Jones, Michael E [0000-0001-7479-3451], Keeman, Renske [0000-0002-5452-9933], Larson, Nicole L [0000-0002-2129-6934], Milne, Roger L [0000-0001-5764-7268], Nevanlinna, Heli [0000-0002-0916-2976], Olson, Janet E [0000-0003-4944-7789], Peterlongo, Paolo [0000-0001-6951-6855], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Rennert, Gad [0000-0002-8512-068X], Tomlinson, Ian [0000-0003-3037-1470], Truong, Thérèse [0000-0002-2943-6786], Vachon, Celine M [0000-0002-1962-9322], Wolk, Alicja [0000-0001-7387-6845], Ziogas, Argyrios [0000-0003-4529-3727], Simard, Jacques [0000-0001-6906-3390], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Wilson, Leila [0000-0003-1214-8080], Clinical Genetics, Medical Oncology, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, and Clinicum

Subjects
endocrine system diseases, 45/43, Medicine (miscellaneous), Genome-wide association studies, Basic medicine, Breast cancer, Other medical sciences, Runx2, Risk Factors, Biology (General), skin and connective tissue diseases, 0303 health sciences, 030305 genetics & heredity, article, 3. Good health, Female, General Agricultural and Biological Sciences, Medical Genetics, Mutations, DNA Copy Number Variations, Locus, QH301-705.5, kConFab/AOCS Investigators, ABCTB Investigators, 631/208/205/2138, Breast Neoplasms, Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, NBCS Collaborators, Association, Deletion, 03 medical and health sciences, SDG 3 - Good Health and Well-being, mental disorders, Humans, 030304 developmental biology, Medicinsk genetik, Cancer och onkologi, Genome, Human, Health sciences, 631/67/1347, CTS Consortium, Germ Cells, Genes, Clinical medicine, Cancer and Oncology, Case-Control Studies, 3111 Biomedicine, Structural variation, Brca1, Genome-Wide Association Study
Abstract

Germline copy 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. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value, 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
2021

5. Discovery of common and rare genetic risk variants for colorectal cancer

Author

Charles M. Connolly, Deborah A. Nickerson, Jian Gong, Sébastien Küry, Barbara Pardini, Brent W. Zanke, Andrea Gsur, Jochen Hampe, Coral Arnau-Collell, M. Henar Alonso, Elio Riboli, Annika Lindblom, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Lori C. Sakoda, Caroline McNeil, Flavio Lejbkowicz, Hyun Min Kang, David J. Hunter, Martha L. Slattery, Miguel Rodríguez-Barranco, Christina Bamia, Satu Männistö, Timothy J. Key, W. James Gauderman, Gonçalo R. Abecasis, Sanford D. Markowitz, Laurence N. Kolonel, Mark A. Jenkins, Yi Lin, Robin Myte, Hedy S. Rennert, Neil Murphy, Antonia Trichopoulou, Christopher I. Li, Ross L. Prentice, Sai Chen, Stephanie J. Weinstein, Kristin E. Anderson, Hua Ling, Mitul Shah, Philipp Hofer, Wen Yi Huang, Sergi Castellví-Bel, Susanna C. Larsson, Maria Dolores Chirlaque, Wei Zheng, Stephanie L. Schmit, Cecelia A. Laurie, Soo-Chin Lee, David Forman, Andrea N. Burnett-Hartman, Giovanna Masala, Sarah C. Nelson, Michael O. Woods, Charles Kooperberg, Qing Zhang, Sonja I. Berndt, Christopher S. Carlson, Katja Butterbach, Hyeong Rok Kim, Rebecca D. Jackson, David Van Den Berg, Michael C. Bassik, Amanda J. Cross, Sushma S. Thomas, Clemens Schafmayer, Anna H. Wu, Douglas F. Easton, Robert W. Haile, Ludmila Vodickova, Graham G. Giles, Yu Ru Su, Jenny Chang-Claude, Lorena Moreno, Peter C. Scacheri, Stefanie Brezina, Min-Ho Shin, Steven Gallinger, Bethany Van Guelpen, Daniel D. Buchanan, Roger L. Milne, Stephen J. Chanock, Tin Louie, Tameka Shelford, Emily White, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Roxann G. Ingersoll, Temitope O. Keku, Stephanie A. Bien, Fredrick R. Schumacher, Wan-Ling Hsu, Amanda E. Toland, John S. Grove, Noralane M. Lindor, Faye Elliott, Leon Raskin, Heather Hampel, Joshua D. Smith, Vicente Martín, David V. Conti, Sjoerd G. Elias, Henk J. van Kranen, Manish Gala, Daniela Seminara, Syed H.E. Zaidi, Suzanne M. Leal, Tilman Kühn, Korbinian Weigl, Marc J. Gunter, Cornelia M. Ulrich, Peyton Greenside, Victor Moreno, John D. Potter, Michael Hoffmeister, Eric J. Jacobs, Catherine M. Tangen, Jihyoun Jeon, Fränzel J.B. Van Duijnhoven, Andrew T. Chan, Stephen B. Gruber, John A. Baron, Alicja Wolk, Edith J. M. Feskens, Demetrius Albanes, Amit Joshi, Bette J. Caan, Polly A. Newcomb, Stéphane Bézieau, Elizabeth M. Gillanders, Anshul Kundaje, Elizabeth A. Platz, Michael Wainberg, Sun-Seog Kweon, C. Roland Wolf, Gemma Ibáñez-Sanz, Shuji Ogino, Emiko Kobayashi, Richard B. Hayes, Patrick S. Parfrey, Katarina Cuk, Stephen N. Thibodeau, Kenneth Offit, David Duggan, Sophia Harlid, Pavel Vodicka, Juergen Boehm, Christa Stegmaier, Jeroen R. Huyghe, Joseph Vijai, Sang-Hee Cho, Elizabeth W. Pugh, Rachel Pearlman, Alessio Naccarati, Marilena Melas, Graham Casey, Jane Romm, Stephan Buch, Phyllis J. Goodman, Albert de la Chapelle, John L. Hopper, Zsofia K. Stadler, Corinne E. Joshu, Liesel M. FitzGerald, Wolfgang Lieb, Aung Ko Win, Keith R. Curtis, Hermann Brenner, Christopher K. Edlund, Li Hsu, Conghui Qu, Peter T. Campbell, Robert E. Schoen, Heiner Boeing, D. Timothy Bishop, Kimberly F. Doheny, Sabina Sieri, Barbara L. Banbury, Mathieu Lemire, Jane C. Figueiredo, Gregory Idos, Katerina Shulman, Thomas J. Hudson, Melissa C. Southey, Duncan C. Thomas, Paul D.P. Pharoah, Mila Pinchev, Vittorio Perduca, Rocky Fischer, Volker Arndt, William M. Grady, Nasa Sinnott-Armstrong, N. Charlotte Onland-Moret, David M. Levine, Li Li, Dallas R. English, Health Research Board - Ireland, Department of Medical Genetics, HMNC Brain Health, Case Western Reserve University [Cleveland], National Cancer Institute, NIH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Division of Cancer Epidemiology, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], Division of Signaling Biology, Ontario Cancer Institute, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), National Institute of Standards and Technology [Gaithersburg] (NIST), Ohio State University [Columbus] (OSU), Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Epidemiology Centre, Cancer Council Victoria, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Northern and Yorkshire Cancer Registry and Information Service, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, London School of Hygiene and Tropical Medicine (LSHTM), Fraunhofer Institute for Manufacturing Engineering and Automation (Fraunhofer IPA), Fraunhofer (Fraunhofer-Gesellschaft), Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Tata Memorial Centre, Cancer Epidemiology Unit, University of Oxford [Oxford], Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, National University Health System, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Dell-EMC, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], University Medical Center [Utrecht], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, Department of Epidemiology and Biostatistics, Imperial College London, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Department of Laboratory Medicine and Department of Pathology, Mayo Clinic College of Medicine, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Dundee Technopole, CXR Biosciences Ltd, Karolinska Institutet [Stockholm], CINTRA / SEEE Nanyang Technological University, Nanyang Technological University [Singapour], Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Department of Preventive Medicine, University of Southern California (USC), Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Medstar Research Institute, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Wageningen University and Research Centre [Wageningen] (WUR), Mount Sinai Hospital (MSH), Fraunhofer Institute for Manufacturing Engineering and Automation [Stuttgart] (IPA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Czech Academy of Sciences [Prague] (ASCR), Huyghe, Jeroen R [0000-0001-6027-9806], Harrison, Tabitha A [0000-0002-4173-7530], Chen, Sai [0000-0003-3106-5643], Schmit, Stephanie L [0000-0001-5931-1194], Jeon, Jihyoun [0000-0001-7003-3412], Schumacher, Fredrick R [0000-0002-3073-7463], Nelson, Sarah C [0000-0002-2109-6465], Sinnott-Armstrong, Nasa A [0000-0003-4490-0601], Alonso, M Henar [0000-0003-0285-5451], Arndt, Volker [0000-0001-9320-8684], Bézieau, Stéphane [0000-0003-0095-1319], Bishop, D Timothy [0000-0002-8752-8785], Brezina, Stefanie [0000-0001-5238-6900], Buchanan, Daniel D [0000-0003-2225-6675], Chanock, Stephen J [0000-0002-2324-3393], de la Chapelle, Albert [0000-0001-9345-9248], Easton, Douglas F [0000-0003-2444-3247], Hampe, Jochen [0000-0002-2421-6127], Hayes, Richard B [0000-0002-0918-661X], Hofer, Philipp [0000-0003-2550-6019], Huang, Wen-Yi [0000-0002-4440-3368], Hudson, Thomas J [0000-0002-1376-4849], Jacobs, Eric J [0000-0002-8458-7659], Jenkins, Mark A [0000-0002-8964-6160], Joshi, Amit D [0000-0001-7581-6934], Küry, Sébastien [0000-0001-5497-0465], Larsson, Susanna C [0000-0003-0118-0341], Laurie, Cecelia A [0000-0001-6569-2501], Martín, Vicente [0000-0003-0552-2804], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger L [0000-0001-5764-7268], Naccarati, Alessio [0000-0001-5774-0905], Newcomb, Polly A [0000-0001-8786-0043], Pardini, Barbara [0000-0001-9571-4257], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul DP [0000-0001-8494-732X], Raskin, Leon [0000-0003-1195-7214], Rennert, Gad [0000-0002-8512-068X], Shin, Min-Ho [0000-0002-2217-5624], Toland, Amanda E [0000-0002-0271-1792], Vijai, Joseph [0000-0002-7933-151X], Weigl, Korbinian [0000-0003-4453-2036], Win, Aung Ko [0000-0002-2794-5261], Wolk, Alicja [0000-0001-7387-6845], Zheng, Wei [0000-0003-1226-070X], Bassik, Michael C [0000-0001-5185-8427], Moreno, Victor [0000-0002-2818-5487], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository

Subjects
Male, Nutrition and Disease, Colorectal cancer, IDENTIFIES 6, Genome-wide association study, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, ComputingMilieux_MISCELLANEOUS, Avaluació del risc per la salut, Genetics & Heredity, Genetics, 0303 health sciences, COLON-CANCER, 11 Medical And Health Sciences, Middle Aged, 3. Good health, Medical genetics, Female, RNA, Long Noncoding, Colorectal Neoplasms, Life Sciences & Biomedicine, Signal Transduction, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Article, Health risk assessment, 03 medical and health sciences, QUALITY-CONTROL, Càncer colorectal, Journal Article, medicine, Life Science, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, VLAG, Aged, 030304 developmental biology, Global Nutrition, [SDV.GEN]Life Sciences [q-bio]/Genetics, Wereldvoeding, Science & Technology, ORGAN SIZE, MUTATIONS, Haplotype, Case-control study, 06 Biological Sciences, medicine.disease, Genetic architecture, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human genome, LYSOPHOSPHATIDIC ACID, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.

Published
2018

6. Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium

Author

Morra, Anna, Jung, Audrey Y, Behrens, Sabine, Keeman, Renske, Ahearn, Thomas U, Anton-Culver, Hoda, Arndt, Volker, Augustinsson, Annelie, Auvinen, Päivi K, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y, Camp, Nicola J, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chanock, Stephen J, Choi, Ji-Yeob, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Egan, Kathleen M, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny N, Hart, Steven N, Hartman, Mikael, Heyworth, Jane S, Hoppe, Reiner, Hopper, John L, Hunter, David J, Ito, Hidemi, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Lacey, James V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lubiński, Jan, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Mavroudis, Dimitrios, Milne, Roger L, Muranen, Taru A, Newman, William G, Noh, Dong-Young, Nordestgaard, Børge G, Obi, Nadia, Olshan, Andrew F, Olsson, Håkan, Park-Simon, Tjoung-Won, Petridis, Christos, Pharoah, Paul DP, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rashid, Muhammad U, Rennert, Gad, Rennert, Hedy S, Rhenius, Valerie, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J, Schneeweiss, Andreas, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Southey, Melissa C, Stram, Daniel O, Tamimi, Rulla M, Tapper, William, Tollenaar, Rob AEM, Tomlinson, Ian, Torres, Diana, Troester, Melissa A, Truong, Thérèse, Vachon, Celine M, Wang, Qin, Wang, Sophia S, Williams, Justin A, Winqvist, Robert, Wolk, Alicja, Wu, Anna H, Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Yang, Xiaohong R, Eliassen, A Heather, Holmes, Michelle D, García-Closas, Montserrat, Teo, Soo Hwang, Schmidt, Marjanka K, Chang-Claude, Jenny, ABCTB Investigators, NBCS Collaborators, Behrens, Sabine [0000-0002-9714-104X], Keeman, Renske [0000-0002-5452-9933], Ahearn, Thomas U [0000-0003-0771-7752], Arndt, Volker [0000-0001-9320-8684], Augustinsson, Annelie [0000-0003-3415-0536], Brenner, Hermann [0000-0002-6129-1572], Camp, Nicola J [0000-0002-4788-1998], Canzian, Federico [0000-0002-4261-4583], Cox, Angela [0000-0002-5138-1099], Dunning, Alison M [0000-0001-6651-7166], Evans, D Gareth [0000-0002-8482-5784], Fasching, Peter A [0000-0003-4885-8471], Gago-Dominguez, Manuela [0000-0001-6713-4351], García-Sáenz, José A [0000-0001-6880-0301], Gaudet, Mia M [0000-0002-6429-4007], Giles, Graham G [0000-0003-4946-9099], Guénel, Pascal [0000-0002-8359-518X], Hall, Per [0000-0002-5640-9126], Hart, Steven N [0000-0001-7714-2734], Hartman, Mikael [0000-0001-5726-9965], Ito, Hidemi [0000-0002-8023-4581], Jager, Agnes [0000-0002-7713-1450], Jakubowska, Anna [0000-0002-5650-0501], Janni, Wolfgang [0000-0001-5911-2400], Kaaks, Rudolf [0000-0003-3751-3929], Kapoor, Pooja Middha [0000-0001-5503-8215], Koutros, Stella [0000-0001-5294-5485], Lambrechts, Diether [0000-0002-3429-302X], Li, Jingmei [0000-0001-8587-7511], Matsuo, Keitaro [0000-0003-1761-6314], Milne, Roger L [0000-0001-5764-7268], Muranen, Taru A [0000-0002-5895-1808], Newman, William G [0000-0002-6382-4678], Park-Simon, Tjoung-Won [0000-0002-2863-3040], Pharoah, Paul DP [0000-0001-8494-732X], Rennert, Gad [0000-0002-8512-068X], Rennert, Hedy S [0000-0001-5772-2977], Rhenius, Valerie [0000-0003-4215-3235], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Schneeweiss, Andreas [0000-0002-2429-4512], Scott, Christopher [0000-0003-1340-0647], Southey, Melissa C [0000-0002-6313-9005], Stram, Daniel O [0000-0001-7099-9022], Tamimi, Rulla M [0000-0003-2306-8668], Tomlinson, Ian [0000-0003-3037-1470], Torres, Diana [0000-0002-9879-9775], Vachon, Celine M [0000-0002-1962-9322], Wolk, Alicja [0000-0001-7387-6845], Ziogas, Argyrios [0000-0003-4529-3727], Holmes, Michelle D [0000-0002-8664-2172], García-Closas, Montserrat [0000-0003-1033-2650], Teo, Soo Hwang [0000-0002-0444-590X], Schmidt, Marjanka K [0000-0002-2228-429X], Chang-Claude, Jenny [0000-0001-8919-1971], and Apollo - University of Cambridge Repository

Subjects
Adult, Risk Factors, Cause of Death, Humans, Breast Neoplasms, Female, Neoplasm Invasiveness, Prospective Studies, Middle Aged, Life Style, Survival Analysis, Aged, Neoplasm Staging
Abstract

BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus 0

Published
2021
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7. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author

Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O’Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Białkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Bertrand, Ophélie, Caputo, Sandrine, Dupré, Anaïs, le Mentec, Marine, Belotti, Muriel, Birot, Anne-Marie, Buecher, Bruno, Fourme, Emmanuelle, Gauthier-Villars, Marion, Golmard, Lisa, Houdayer, Claude, Moncoutier, Virginie, de Pauw, Antoine, Saule, Claire, Sinilnikova, Olga, Mazoyer, Sylvie, Damiola, Francesca, Barjhoux, Laure, Verny-Pierre, Carole, Léone, M. lanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Caron, Olivier, Guillaud-Bataille, Marine, Bressac-de-Paillerets, Brigitte, Bignon, Yves- Jean, Uhrhammer, Nancy, Lasset, Christine, Bonadona, Valérie, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Noguchi, Tetsuro, Popovici, Cornel, Sobol, Hagay, Bourdon, Violaine, Remenieras, Audrey, Noguès, Catherine, Coupier, Isabelle, Pujol, Pascal, Dumont, Aurélie, Révillion, Françoise, Adenis, Claude, Muller, Danièle, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Leroux, Dominique, Dreyfus, H. lène, Rebischung, Christine, Peysselon, Magalie, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Ferrer, Sandra Fert, Mari, V. ronique, Vénat-Bouvet, Laurence, Delnatte, Capucine, Bézieau, Stéphane, Mortemousque, Isabelle, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Sokolowska, Johanna, Bronner, Myriam, Collonge-Rame, Marie-Agnès, Damette, Alexandre, Gesta, Paul, Lallaoui, Hakima, Chiesa, Jean, Molina-Gomes, Denise, Ingster, Olivier, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Ong, Kai-ren, Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brewer, Carole, Davidson, Rosemarie, Izatt, Louise, Brady, Angela, Barwell, Julian, Adlard, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Eeles, Rosalind A., Cook, Jackie, Snape, Katie, Eccles, Diana, Murray, Alex, McCann, Emma, Collée, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dörk, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, García-Closas, Montserrat, García-Sáenz, José A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Greene, Mark H., Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Fox, Stephen, Campbell, Ian, Spurdle, Amanda, Webb, Penny, de Fazio, Anna, Tassell, Margaret, Kirk, Judy, Lindeman, Geoff, Price, Melanie, Southey, Melissa, Milne, Roger, Deb, Sid, Bowtell, David, van der Hout, Annemieke H., van den Ouweland, Ans M. W., Mensenkamp, Arjen R., van Deurzen, Carolien H. M., Kets, Carolien M., Seynaeve, Caroline, van Asperen, Christi J., Aalfs, Cora M., Gómez Garcia, Encarna B., van Leeuwen, Flora E., de Bock, G. H., Meijers-Heijboer, Hanne E. J., Obdeijn, Inge M., Gille, J. J. P., Oosterwijk, Jan C., Wijnen, Juul T., van der Kolk, Lizet E., Hooning, Maartje J., Ausems, Margreet G. E. M., Mourits, Marian J. E., Blok, Marinus J., Rookus, Matti A., van der Luijt, Rob B., van Cronenburg, T. C. T. E. F., van der Pol, Carmen C., Russell, Nicola S., Siesling, Sabine, Overbeek, Lucy, Wijnands, R., de Lange, Judith L., Clarke, Christine, Graham, Dinny, Sachchithananthan, Mythily, Marsh, Deborah, Scott, Rodney, Baxter, Robert, Yip, Desmond, Carpenter, Jane, Davis, Alison, Pathmanathan, Nirmala, Simpson, Peter, Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernández, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O’Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, H. kan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Pujana, Miquel Angel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teulé, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Thérèse, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., German Cancer Research Center, National Health and Medical Research Council (Australia), United States of Department of Health & Human Services, National Institute for Health Research (Reino Unido), French National Cancer Institute, Ligue Nationale Contre le Cancer (Francia), Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea, Canadian Institutes of Health Research, Cancer Council New South Wales (Australia), KWF Kankerbestrijding, Instituto de Salud Carlos III, Xunta de Galicia (España), Ministerio de Sanidad, Política Social e Igualdad (España), Helmholtz Association, California Breast Cancer Research Program, Federal Ministry of Education & Research (Alemania), Government of Netherlands, Russian Foundation for Basic Research, O’Mara, Tracy A. [0000-0002-5436-3232], Dennis, Joe [0000-0003-4591-1214], Tyrer, Jonathan P. [0000-0003-3724-4757], Barnes, Daniel R. [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Ahearn, Thomas [0000-0003-0771-7752], Andrulis, Irene L. [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Azzollini, Jacopo [0000-0002-9364-9778], Barrowdale, Daniel [0000-0003-1661-3939], Becher, Heko [0000-0002-8808-6667], Bernstein, Leslie [0000-0002-7692-6518], Bojesen, Stig E. [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Caldés, Trinidad [0000-0002-1038-5392], Chanock, Stephen J. [0000-0002-2324-3393], Chung, Wendy K. [0000-0003-3438-5685], Claes, Kathleen B. M. [0000-0003-0841-7372], Collée, J. Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dunning, Alison M. [0000-0001-6651-7166], Dwek, Miriam [0000-0001-7184-2932], Eliassen, A. Heather [0000-0002-3961-6609], Fritschi, Lin [0000-0002-7692-3560], García-Closas, Montserrat [0000-0003-1033-2650], García-Sáenz, José A. [0000-0001-6880-0301], Gayther, Simon A. [0000-0001-7937-5443], Giles, Graham G. [0000-0003-4946-9099], Greene, Mark H. [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Håkansson, Niclas [0000-0001-7673-5554], Hart, Steven N. [0000-0001-7714-2734], He, Wei [0000-0003-0161-3274], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J. [0000-0001-8397-4078], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A. [0000-0002-4361-4657], Jensen, Uffe Birk [0000-0002-6205-6355], Jones, Michael E. [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Kraft, Peter [0000-0002-4472-8103], Kurian, Allison W. [0000-0002-6175-9470], Lambrechts, Diether [0000-0002-3429-302X], Lesueur, Fabienne [0000-0001-7404-4549], Martens, John W. M. [0000-0002-3428-3366], Miller, Austin [0000-0001-9739-8462], Milne, Roger L. [0000-0001-5764-7268], Nathanson, Katherine L. [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I. [0000-0002-9936-1599], Olson, Janet E. [0000-0003-4944-7789], Ottini, Laura [0000-0001-8030-0449], Parsons, Michael T. [0000-0003-3242-8477], Pedersen, Inge Sokilde [0000-0002-9902-8040], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Pharoah, Paul D. P. [0000-0001-8494-732X], Punie, Kevin [0000-0002-1162-7963], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Sandler, Dale P. [0000-0002-6776-0018], Schmidt, Marjanka K. [0000-0002-2228-429X], Scott, Christopher [0000-0003-1340-0647], Stone, Jennifer [0000-0001-5077-0124], Toland, Amanda E. [0000-0002-0271-1792], Truong, Thérèse [0000-0002-2943-6786], Vachon, Celine M. [0000-0002-1962-9322], Vega, Ana [0000-0002-7416-5137], Vijai, Joseph [0000-0002-7933-151X], Weitzel, Jeffrey N. [0000-0001-6714-092X], Wolk, Alicja [0000-0001-7387-6845], Yadav, Siddhartha [0000-0003-4630-9903], Yannoukakos, Drakoulis [0000-0001-7509-3510], Ziogas, Argyrios [0000-0003-4529-3727], Zorn, Kristin K. [0000-0003-2143-8979], Park, Sue K. [0000-0001-5002-9707], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F. [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Becher, Heiko [0000-0002-8808-6667], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, German Cancer Research Center (DKFZ), National Health and Medical Research Council of Australia, United States Department of Health & Human Services National Institutes of Health (NIH) - USA, National Institute for Health Research (NIHR), Institut National du Cancer (INCA) France, Ligue nationale contre le cancer, Cancer Research UK, European Commision, Canadian Institutes of Health Research (CIHR), Cancer Council New South Wales, Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud, Xunta de Galicia, Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain, Fondo de Investigacion Sanitario, California Breast Cancer Research Fund, Federal Ministry of Education & Research (BMBF), Netherlands Government, Russian Foundation for Basic Research (RFBR), O'Mara, Tracy A [0000-0002-5436-3232], Tyrer, Jonathan P [0000-0003-3724-4757], Barnes, Daniel R [0000-0002-3781-7570], Andrulis, Irene L [0000-0002-4226-6435], Bojesen, Stig E [0000-0002-4061-4133], Chanock, Stephen J [0000-0002-2324-3393], Chung, Wendy K [0000-0003-3438-5685], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Dunning, Alison M [0000-0001-6651-7166], Eliassen, A Heather [0000-0002-3961-6609], García-Sáenz, José A [0000-0001-6880-0301], Gayther, Simon A [0000-0001-7937-5443], Giles, Graham G [0000-0003-4946-9099], Greene, Mark H [0000-0003-1852-9239], Hart, Steven N [0000-0001-7714-2734], Hulick, Peter J [0000-0001-8397-4078], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kurian, Allison W [0000-0002-6175-9470], Martens, John WM [0000-0002-3428-3366], Milne, Roger L [0000-0001-5764-7268], Nathanson, Katherine L [0000-0002-6740-0901], Olopade, Olufunmilayo I [0000-0002-9936-1599], Olson, Janet E [0000-0003-4944-7789], Parsons, Michael T [0000-0003-3242-8477], Pharoah, Paul DP [0000-0001-8494-732X], Sandler, Dale P [0000-0002-6776-0018], Schmidt, Marjanka K [0000-0002-2228-429X], Toland, Amanda E [0000-0002-0271-1792], Vachon, Celine M [0000-0002-1962-9322], Weitzel, Jeffrey N [0000-0001-6714-092X], Zorn, Kristin K [0000-0003-2143-8979], Park, Sue K [0000-0001-5002-9707], Easton, Douglas F [0000-0003-2444-3247], HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Institut Català de la Salut, [Coignard J] Genetic Epidemiology of Cancer team, Inserm, U900, Paris, France. Institut Curie Paris, Paris, France. Mines ParisTech Fontainebleau, Paris, France. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. PSL University Paris, Paris, France. Paris Sud University, Orsay, France. [Lush M, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Beesley J, O'Mara TA] Department of Genetics and Computational Biology QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. [Tyrer JP] Centre for Cancer Genetic Epidemiology, Department of Oncology University of Cambridge, Cambridge, UK. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Lopez-Fernández A] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Human Genetics, ARD - Amsterdam Reproduction and Development, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Cancer biology and immunology, Clinical Genetics, Medical Oncology, Pathology, and Radiology & Nuclear Medicine

Subjects
0301 basic medicine, Linkage disequilibrium, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], 45/43, General Physics and Astronomy, Genome-wide association study, Linkage Disequilibrium, Breast cancer, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Risk Factors, Genotype, breast neoplasms, Medicine and Health Sciences, 631/208/68, skin and connective tissue diseases, Cancer genetics, adult, alleles, BRCA1 protein, BRCA2 protein, female, genetic predisposition to disease, genome-wide association study, genotype, humans, linkage disequilibrium, middle aged, mutation, quantitative trait loci, risk factors, polymorphism, single nucleotide, HEBON Investigators, Genetics, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], education.field_of_study, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, Otros calificadores::Otros calificadores::/genética [Otros calificadores], BRCA1 Protein, Genetic Predisposition to Disease/genetics, article, Single Nucleotide, Middle Aged, BRCA2 Protein/genetics, 3. Good health, Mama - Càncer - Factors de risc, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Genome-Wide Association Study/methods, Medical genetics, Female, Medical Genetics, 692/499, Adult, medicine.medical_specialty, 45/61, Science, 3122 Cancers, Population, Quantitative Trait Loci, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], ABCTB Investigators, 631/67/2324, Breast Neoplasms, Biology, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Càncer de mama, GEMO Study Collaborators, 03 medical and health sciences, Cancer epidemiology, SDG 3 - Good Health and Well-being, Other subheadings::Other subheadings::/genetics [Other subheadings], medicine, Humans, Genetic Predisposition to Disease, Allele, Polymorphism, education, EMBRACE Collaborators, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Alleles, Medicinsk genetik, BRCA2 Protein, Mutació (Biologia), General Chemistry, 631/67/1347, Genotype frequency, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, BRCA1 Protein/genetics, 3111 Biomedicine, KConFab Investigators, Quantitative Trait Loci/genetics, Genètica, Genome-Wide Association Study
Abstract

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, Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Published
2021

8. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author

Fachal, L., Aschard, H., Beesley, J., Barnes, D.R., Allen, J., Kar, S., Pooley, K.A., Dennis, J., Michailidou, K., Turman, C., Soucy, P., Lemaçon, A., Lush, M., Tyrer, J.P., Ghoussaini, M., Marjaneh, M.M., Jiang, X., Agata, S., Aittomäki, K., Alonso, M.R., Andrulis, I.L., Anton-Culver, H., Antonenkova, N.N., Arason, A., Arndt, V., Aronson, K.J., Arun, B.K., Auber, B., Auer, P.L., Azzollini, J., Balmaña, J., Barkardottir, R.B., Barrowdale, D., Beeghly-Fadiel, A., Benitez, J., Bermisheva, M., Białkowska, K., Blanco, A.M., Blomqvist, C., Blot, W., Bogdanova, N.V., Bojesen, S.E., Bolla, M.K., Bonanni, B., Borg, A., Bosse, K., Brauch, H., Brenner, H., Briceno, I., Brock, I.W., Brooks-Wilson, A., Brüning, T., Burwinkel, B., Buys, S.S., Cai, Q., Caldés, T., Caligo, M.A., Camp, N.J., Campbell, I., Canzian, F., Carroll, J.S., Carter, B.D., Castelao, J.E., Chiquette, J., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Mari, V., Berthet, P., Castera, L., Vaur, D., Lallaoui, H., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Lasset, C., Révillion, F., Vennin, P., Muller, D., Gomes, D.M., Ingster, O., Coupier, I., Pujol, P., Collonge-Rame, M.-A., Mortemousque, I., Bera, O., Rose, M., Baurand, A., Bertolone, G., Faivre, L., Dreyfus, H., Leroux, D., Venat-Bouvet, L., Bézieau, S., Delnatte, C., Chiesa, J., Gilbert-Dussardier, B., Gesta, P., Prieur, F.P., Bronner, M., Sokolowska, J., Coulet, F., Boutry-Kryza, N., Calender, A., Giraud, S., Leone, M., Fert-Ferrer, S., Stoppa-Lyonnet, D., Jiao, Y., Lesueur, F.L., Mebirouk, N., Barouk-Simonet, E., Bubien, V., Longy, M., Sevenet, N., Gladieff, L., Toulas, C., Reimineras, A., Sobol, H., Paillerets, B.B.-D., Cabaret, O., Caron, O., Guillaud-Bataille, M., Rouleau, E., Belotti, M., Buecher, B., Caputo, S., Colas, C., Pauw, A.D., Fourme, E., Gauthier-Villars, M., Golmard, L., Moncoutier, V., Saule, C., Donaldson, A., Murray, A., Brady, A., Brewer, C., Pottinger, C., Miller, C., Gallagher, D., Gregory, H., Cook, J., Eason, J., Adlard, J., Barwell, J., Ong, K.-R., Snape, K., Walker, L., Izatt, L., Side, L., Tischkowitz, M., Rogers, M.T., Porteous, M.E., Ahmed, M., Morrison, P.J., Brennan, P., Eeles, R., Davidson, R., Collée, M., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Cybulski, C., Czene, K., Daly, M.B., de la Hoya, M., Devilee, P., Diez, O., Ding, Y.C., Dite, G.S., Domchek, S.M., Dörk, T., dos-Santos-Silva, I., Droit, A., Dubois, S., Dumont, M., Duran, M., Durcan, L., Dwek, M., Eccles, D.M., Engel, C., Eriksson, M., Evans, D.G., Fasching, P.A., Fletcher, O., Floris, G., Flyger, H., Foretova, L., Foulkes, W.D., Friedman, E., Fritschi, L., Frost, D., Gabrielson, M., Gago-Dominguez, M., Gambino, G., Ganz, P.A., Gapstur, S.M., Garber, J., García-Sáenz, J.A., Gaudet, M.M., Georgoulias, V., Giles, G., Glendon, G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., González-Neira, A., Tibiletti, M.G., Greene, M.H., Grip, M., Gronwald, J., Grundy, A., Guénel, P., Hahnen, E., Haiman, C.A., Håkansson, N., Hall, 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Jakubowska, A., James, P.A., Janavicius, R., Jankowitz, R.C., John, E.M., Johnson, N., Jones, M.E., Jukkola-Vuorinen, A., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Karlan, B.Y., Keeman, R., Kerin, M.J., Khusnutdinova, E., Kiiski, J.I., Kitahara, C.M., Ko, Y.-D., Konstantopoulou, I., Kosma, V.-M., Koutros, S., Kubelka-Sabit, K., Kwong, A., Kyriacou, K., Laitman, Y., Lambrechts, D., Lee, E., Leslie, G., Lester, J., Lesueur, F., Lindblom, A., Lo, W.-Y., Long, J., Lophatananon, A., Loud, J.T., Lubiński, J., MacInnis, R.J., Maishman, T., Makalic, E., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matsuo, K., Maurer, T., Mavroudis, D., Mayes, R., McGuffog, L., McLean, C., Meindl, A., Miller, A., Miller, N., Montagna, M., Moreno, F., Muir, K., Mulligan, A.M., Muñoz-Garzon, V.M., Muranen, T.A., Narod, S.A., Nassir, R., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Nielsen, F.C., Nikitina-Zake, L., Norman, A., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Osorio, A., Pankratz, V.S., Papp, J., Park, S.K., Park-Simon, T.-W., Parsons, M.T., Paul, J., Pedersen, I.S., Peissel, B., Peshkin, B., Peterlongo, P., Peto, J., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Presneau, N., Prokofyeva, D., Pujana, M.A., Pylkäs, K., Radice, P., Ramus, S.J., Rantala, J., Rau-Murthy, R., Rennert, G., Risch, H.A., Robson, M., Romero, A., Rossing, M., Saloustros, E., Sánchez-Herrero, E., Sandler, D.P., Santamariña, M., Sawyer, E.J., Scheuner, M.T., Schmidt, D.F., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schöttker, B., Schürmann, P., Scott, R.J., Senter, L., Seynaeve, C.M., Shah, M., Sharma, P., Shen, C.-Y., Shu, X.-O., Singer, C.F., Slavin, T.P., Smichkoska, S., Southey, M.C., Spinelli, J.J., Spurdle, A.B., Sutter, C., Swerdlow, A.J., Tamimi, R.M., Tan, Y.Y., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Tengström, M., Teo, S.H., Terry, M.B., Teulé, A., Thomassen, M., Thull, D.L., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Torres-Mejía, G., Troester, M.A., Truong, T., Tung, N., Tzardi, M., Ulmer, H.-U., Vachon, C.M., van der Kolk, L.E., van Rensburg, E.J., Vega, A., Viel, A., Vijai, J., Vogel, M.J., Wang, Q., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wendt, C., Wildiers, H., Winqvist, R., Wolk, A., Wu, A.H., Yannoukakos, D., Zhang, Y., Zheng, W., Hunter, D., Pharoah, P.D.P., Chang-Claude, J., García-Closas, M., Schmidt, M.K., Kristensen, V.N., French, J.D., Edwards, S.L., Antoniou, A.C., Simard, J., Easton, D.F., Kraft, P., Dunning, A.M., Collaborators, GEMO Study, Collaborators, EMBRACE, Investigators, KConFab, Investigators, HEBON, Investigators, ABCTB, Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Duijf, Pascal, Dunning, Alison M, GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Klinische Genetica, MUMC+: DA KG Polikliniek (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), European Commission, Government of Canada, Canadian Institutes of Health Research, National Institutes of Health (US), Cancer Research UK, Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, University of Cambridge [UK] (CAM), NSCAD, University of Cyprus [Nicosia], Harvard T.H. Chan School of Public Health, This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation), the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492), and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note., We thank all of the individuals who took part in these studies, as well as all of the researchers, clinicians, technicians and administrative staff who enabled this work to be carried out, European Project: 656144,H2020,H2020-MSCA-IF-2014,RADIOGENFF(2016), European Project: 223175,EC:FP7:HEALTH,FP7-HEALTH-2007-B,COGS(2009), European Project: 633784,H2020,H2020-PHC-2014-two-stage,B-CAST(2015), European Project: 634935,H2020,H2020-PHC-2014-two-stage,BRIDGES(2015), Clinical Genetics, Medical Oncology, Pathology, Radiology & Nuclear Medicine, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia] (UCY), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Targeted Gynaecologic Oncology (TARGON), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Aschard, Hugues [0000-0002-7554-6783], Barnes, Daniel R [0000-0002-3781-7570], Dennis, Joe [0000-0003-4591-1214], Michailidou, Kyriaki [0000-0001-7065-1237], Lemaçon, Audrey [0000-0002-1817-7029], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arndt, Volker [0000-0001-9320-8684], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Campbell, Ian [0000-0002-7773-4155], Carroll, Jason S [0000-0003-3643-0080], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Fletcher, Olivia [0000-0001-9387-7116], Floris, Giuseppe [0000-0003-2391-5425], Foulkes, William D [0000-0001-7427-4651], García-Sáenz, José A [0000-0001-6880-0301], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Matsuo, Keitaro [0000-0003-1761-6314], McLean, Catriona [0000-0002-0302-5727], Miller, Austin [0000-0001-9739-8462], Muir, Kenneth [0000-0001-6429-988X], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Pankratz, V Shane [0000-0002-3742-040X], Parsons, Michael T [0000-0003-3242-8477], Paul, James [0000-0001-7367-5816], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Pylkäs, Katri [0000-0002-2449-0521], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher [0000-0003-1340-0647], Scott, Rodney J [0000-0001-7724-3404], Spurdle, Amanda B [0000-0003-1337-7897], Stone, Jennifer [0000-0001-5077-0124], Sutter, Christian [0000-0003-4051-5888], Tan, Yen Yen [0000-0003-1063-5352], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Pharoah, Paul DP [0000-0001-8494-732X], Schmidt, Marjanka K [0000-0002-2228-429X], Milne, Roger L [0000-0001-5764-7268], Edwards, Stacey L [0000-0001-7428-4139], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Kraft, Peter [0000-0002-4472-8103], Dunning, Alison M [0000-0001-6651-7166], Apollo - University of Cambridge Repository, Academic Medical Center, ARD - Amsterdam Reproduction and Development, Human genetics, CCA - Cancer biology and immunology, Molecular cell biology and Immunology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Doctoral Programme in Clinical Research, Staff Services, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, and Department of Obstetrics and Gynecology

Subjects
CHROMATIN, Linkage disequilibrium, Genome-wide association study, Regulatory Sequences, Nucleic Acid, Genome-wide association studies, Linkage Disequilibrium, Basic medicine, 0302 clinical medicine, Breast cancer, MESH: Risk Factors, Risk Factors, COMPREHENSIVE MOLECULAR PORTRAITS, 11 Medical and Health Sciences, HEBON Investigators, Genetics & Heredity, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], PROTEIN FUNCTION, Tumor, breast tumor, MESH: Polymorphism, Single Nucleotide, 1184 Genetics, developmental biology, physiology, MESH: Genetic Predisposition to Disease, apoptosis, Chromosome Mapping, Single Nucleotide, 3. Good health, MESH: Linkage Disequilibrium, Female, MESH: Biomarkers, Tumor, Biomarkers, Tumor/genetics, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Life Sciences & Biomedicine, SUSCEPTIBILITY LOCI, MESH: Bayes Theorem, Quantitative Trait Loci, ABCTB Investigators, INTEGRATIVE ANALYSIS, Breast Neoplasms, Computational biology, Biology, Quantitative trait locus, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, Article, ENHANCER, GEMO Study Collaborators, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, REVEALS, Genetics, Biomarkers, Tumor, MESH: Regulatory Sequences, Nucleic Acid, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, FUNCTIONAL VARIANTS, EMBRACE Collaborators, Gene, 030304 developmental biology, Genetic association, Bayes Theorem, Genome-Wide Association Study, MESH: Humans, Science & Technology, Nucleic Acid, gene mapping, 06 Biological Sciences, MESH: Quantitative Trait Loci, DNA binding site, ESTROGEN-RECEPTOR, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Clinical medicine, Expression quantitative trait loci, MESH: Genome-Wide Association Study, Human genome, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, KConFab Investigators, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Chromosome Mapping, Chromosome Mapping/methods, Regulatory Sequences, MESH: Female, Biomarkers, 030217 neurology & neurosurgery, MESH: Breast Neoplasms, Developmental Biology
Abstract

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., This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation); the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE; part of the GAME-ON initiative).

Published
2020

9. Two truncating variants in FANCC and breast cancer risk

Author

Dork, T., Peterlongo, P., Mannermaa, A., Bolla, M.K., Wang, Q., Dennis, J., Ahearn, T., Andrulis, I.L., Anton-Culver, H., Arndt, V., Aronson, K.J., Augustinsson, A., Freeman, L.E.B., Beckmann, M.W., Beeghly-Fadiel, A., Behrens, S., Bermisheva, M., Blomqvist, C., Bogdanova, N., Bojesen, S.E., Brauch, H., Brenner, H., Burwinkel, B., Canzian, F., Chan, T.L., Chang-Claude, J., Chanock, S.J., Choi, J.Y., Christiansen, H., Clarke, C.L., Couch, F.J., Czene, K., Daly, M.B., dos-Santos-Silva, I., Dwek, M., Eccles, D.M., Ekici, A.B., Eriksson, M., Evans, D.G., Fasching, P.A., Figueroa, J., Flyger, H., Fritschisl, L., Gabrielson, M., Gago-Dominguez, M., Gao, C., Gapstur, S.M., Garcia-Closas, M., Garcia-Saenz, J.A., Gaudet, M.M., Giles, G.G., Goldberg, M.S., Goldgar, D.E., Guenel, P., Haeberle, L., Haiman, C.A., Hakansson, N., Hall, P., Hamann, U., Hartman, M., Hauke, J., Hein, A., Hillemanns, P., Hogervorst, F.B.L., Hooning, M.J., Hopper, J.L., Howell, T., Huo, D.Z., Ito, H., Iwasaki, M., Jakubowska, A., Janni, W., John, E.M., Jung, A., Kaaks, R., Kang, D., Kapoor, P.M., Khusnutdinova, E., Kim, S.W., Kitahara, C.M., Koutros, S., Kraft, P., Kristensen, V.N., Kwon, A., Lambrechts, D., Marchand, L. le, Li, J.M., Lindstrom, S., Linet, M., W.Y. lo, Long, J.R., Lophatananon, A., Lubinski, J., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, E., Matsuo, K., Mavroudis, D., Meindl, A., Menon, U., Milne, R.L., Taib, N.A.M., Muir, K., Mulligan, A.M., Neuhausen, S.L., Nevanlinna, H., Neven, P., Newman, W.G., Offit, K., Olopade, O.I., Olshan, A.F., Olson, J.E., Olsson, H., Park, S.K., Park-Simon, T.W., Peto, J., Plaseska-Karanfilska, D., Pohl-Rescigno, E., Presneau, N., Rack, B., Radice, P., Rashid, M.U., Rennert, G., Rennert, H.S., Romero, A., Ruebner, M., Saloustros, E., Schmidt, M.K., Schmutzler, R.K., Schneider, M.O., Schoemaker, M.J., Scott, C., Shen, C.Y., Shu, X.O., Simard, J., Slager, S., Smichkoska, S., Southey, M.C., Spinelli, J.J., Stone, J., Surowy, H., Swerdlow, A.J., Tamimi, R.M., Tapper, W.J., Teo, S.H., Terry, M.B., Toland, A.E., Tollenaar, R.A.E.M., Torres, D., Torres-Mejia, G., Troester, M.A., Truong, T., Tsugane, S., Untch, M., Vachon, C.M., Ouweland, A.M.W. van den, Veen, E.M. van, Vijai, J., Wendt, C., Wolk, A., Yu, J.C., Zheng, W., Ziogas, A., Ziv, E., Dunning, A.M., Pharoah, P.D.P., Schindler, D., Devilee, P., Easton, D.F., Balleine, R., Baxter, R., Braye, S., Carpenter, J., Dahlstrom, J., Forbes, J., Lee, C.S., Marsh, D., Morey, A., Pathmanathan, N., Scott, R., Simpson, P., Spigelman, A., Wilcken, N., Yip, D., Zeps, N., Borresen-Dale, A.L., Alnaes, G.I.G., Sahlberg, K.K., Ottestad, L., Karesen, R., Schlichting, E., Holmen, M.M., Sauer, T., Haakensen, V., Engebraten, O., Naume, B., Fossa, A., Kiserud, C.E., Reinertsen, K.V., Helland, A., Riis, M., Geisler, J., ABCTB Investigators, NBCS Collaborators, Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Brauch, Hiltrud [0000-0001-7531-2736], Dwek, Miriam [0000-0001-7184-2932], Ekici, Arif B [0000-0001-6099-7066], Fasching, Peter A [0000-0003-4885-8471], Figueroa, Jonine [0000-0002-5100-623X], Hein, Alexander [0000-0003-2601-3398], Ito, Hidemi [0000-0002-8023-4581], Matsuo, Keitaro [0000-0003-1761-6314], Menon, Usha [0000-0003-3708-1732], Milne, Roger L [0000-0001-5764-7268], Muir, Kenneth [0000-0001-6429-988X], Nevanlinna, Heli [0000-0002-0916-2976], Newman, William G [0000-0002-6382-4678], Peto, Julian [0000-0002-1685-8912], Rennert, Gad [0000-0002-8512-068X], Romero, Atocha [0000-0002-1634-7397], Schmidt, Marjanka K [0000-0002-2228-429X], Scott, Christopher [0000-0003-1340-0647], Stone, Jennifer [0000-0001-5077-0124], Truong, Thérèse [0000-0002-2943-6786], Tsugane, Shoichiro [0000-0003-4105-2774], Ziogas, Argyrios [0000-0003-4529-3727], Dunning, Alison M [0000-0001-6651-7166], Pharoah, Paul DP [0000-0001-8494-732X], Devilee, Peter [0000-0002-8023-2009], Easton, Douglas F [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Andrulis, Irene L. [0000-0002-4226-6435], Ekici, Arif B. [0000-0001-6099-7066], Fasching, Peter A. [0000-0003-4885-8471], Milne, Roger L. [0000-0001-5764-7268], Newman, William G. [0000-0002-6382-4678], Schmidt, Marjanka K. [0000-0002-2228-429X], Dunning, Alison M. [0000-0001-6651-7166], Pharoah, Paul D. P. [0000-0001-8494-732X], Easton, Douglas F. [0000-0003-2444-3247], HUS Comprehensive Cancer Center, Clinicum, University Management, Department of Oncology, University of Helsinki, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, Medical Oncology, and Clinical Genetics

Subjects
0301 basic medicine, Oncology, PROTEIN, lcsh:Medicine, 45/47, 0302 clinical medicine, Fanconi anemia, Genotype, lcsh:Science, Sequence Deletion, Multidisciplinary, BRCA1 Protein, Fanconi Anemia Complementation Group C Protein, 1184 Genetics, developmental biology, physiology, BRCA2 Protein, 3. Good health, BIALLELIC MUTATIONS, DNA-REPAIR, Female, 692/499, Medical Genetics, medicine.medical_specialty, PALB2, 3122 Cancers, ABCTB Investigators, Breast Neoplasms, FANCONIS ANEMIA, Article, 692/4028, NBCS Collaborators, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, NONSENSE MUTATION, Genetic Predisposition to Disease, Medicinsk genetik, 45, business.industry, Genetic heterogeneity, lcsh:R, Case-control study, Genetic Variation, Odds ratio, medicine.disease, GENE, Fanconi Anemia, 030104 developmental biology, Risk factors, Case-Control Studies, lcsh:Q, 3111 Biomedicine, business, 030217 neurology & neurosurgery
Abstract

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

Published
2019

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