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1. Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

Author: Levi, Hagai, Carmi, Shai, Rosset, Saharon, Yerushalmi, Rinat, Zick, Aviad, Yablonski-Peretz, Tamar, Consortium, The BCAC, Wang, Qin, Bolla, Manjeet K, Dennis, Joe, Michailidou, Kyriaki, Lush, Michael, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Arndt, Volker, Augustinsson, Annelie, Auvinen, Päivi, Freeman, Laura Beane, Beckmann, Matthias, Behrens, Sabine, Bermisheva, Marina, Bodelon, Clara, Bogdanova, Natalia V, Bojesen, Stig E, Brenner, Hermann, Byers, Helen, Camp, Nicola, Castelao, Jose, Chang-Claude, Jenny, Chirlaque, María-Dolores, Chung, Wendy, Clarke, Christine, Collaborators, NBCS, Collee, Margriet J, Colonna, Sarah, Consortium, CTS, Couch, Fergus, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary, Devilee, Peter, Dork, Thilo, Dossus, Laure, Eccles, Diana M, Eliassen, A Heather, Eriksson, Mikael, Evans, Gareth, Fasching, Peter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Garcia-Saenz, Jose Angel, Genkinger, Jeanine, Giles, Graham G, Goldberg, Mark, Guénel, Pascal, Hall, Per, Hamann, Ute, He, Wei, Hillemanns, Peter, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John, Investigators, ABCTB, Jakovchevska, Simona, Jakubowska, Anna, Jernström, Helena, John, Esther, Johnson, Nichola, Jones, Michael, Vijai, Joseph, Kaaks, Rudolf, Khusnutdinova, Elza, Kitahara, Cari, Koutros, Stella, Kristensen, Vessela, Kurian, Allison W, Lacey, James, Lambrechts, Diether, Le Marchand, Loic, Lejbkowicz, Flavio, Lindblom, Annika, Loibl, Sibylle, Lori, Adriana, Lubinski, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Mavroudis, Dimitrios, Menon, Usha, Mulligan, AnnaMarie, Murphy, Rachel, Nevelsteen, Ines, Newman, William G, and Obi, Nadia
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Breast Cancer, Prevention, Cancer, Humans, Female, Breast Neoplasms, Genome-Wide Association Study, Jews, Israel, Genetic Predisposition to Disease, Risk Factors, Multifactorial Inheritance, Transcription Factors, Genomics, Polymorphism, Genetic, BCAC Consortium, NBCS Collaborators, CTS Consortium, ABCTB Investigators, Polymorphism, Genetic, Medical and Health Sciences, Genetics & Heredity, Clinical sciences
Abstract: BackgroundPolygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.MethodsWe generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.ResultsIn the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).ConclusionsExtant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
Published: 2023

2. Mitochondrial DNA Variations in Russian and Belorussian Populations

Author: Belyaeva, Olga, Bermisheva, Marina, Khrunin, Andrey, Slominsky, Petr, Bebyakova, Natalia, Khusnutdinova, Ė. K. (Ėlʹza Kamilevna), Mikulich, Aleksei Ignatevich, and Limborskaia, S. A. (Svetlana Andreevna)
Published: 2003
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3. Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

Author: Lopes Cardozo, Josephine MN, Andrulis, Irene L, Bojesen, Stig E, Dörk, Thilo, Eccles, Diana M, Fasching, Peter A, Hooning, Maartje J, Keeman, Renske, Nevanlinna, Heli, Rutgers, Emiel JT, Easton, Douglas F, Hall, Per, Pharoah, Paul DP, van 't Veer, Laura J, Schmidt, Marjanka K, Ahearn, Thomas U, Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L, Augustinsson, Annelie, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bolla, Manjeet K, Bonanni, Bernardo, Boyle, Terry, Brenner, Hermann, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Camp, Nicola J, Canzian, Federico, Cardoso, Fatima, Castelao, Jose E, Cessna, Melissa H, Chan, Tsun L, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Choi, Ji-Yeob, Colonna, Sarah V, Copson, Ellen, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Dennis, Joe, Devilee, Peter, Drukker, Caroline A, Dunning, Alison M, Dwek, Miriam, Eliassen, A Heather, Engel, Christoph, Evans, D Gareth, Figueroa, Jonine D, Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Genkinger, Jeanine, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Gündert, Melanie, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette AM, Hein, Alexander, Ho, Weang-Kee, Hoppe, Reiner, Hopper, John L, Houlston, Richard S, Howell, Anthony, Hunter, David J, Ito, Hidemi, Jakubowska, Anna, Jernström, Helena, John, Esther M, Johnson, Nichola, Jones, Michael E, Joseph, Vijai, Kaaks, Rudolf, Kang, Daehee, Kim, Sung-Won, Kitahara, Cari M, Koppert, Linetta B, Kosma, Veli-Matti, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, and Koutros, Stella
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Good Health and Well Being, Female, Humans, Breast Neoplasms, Risk Factors, Prognosis, Proportional Hazards Models, Breast, Breast Cancer Association Consortium and MINDACT Collaborators, Clinical Sciences, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: PurposeA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.MethodsWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.ResultsThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.ConclusionAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.
Published: 2023

4. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Mueller, Stefanie H, Lai, Alvina G, Valkovskaya, Maria, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Lush, Michael, Abu-Ful, Zomoruda, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baert, Thais, Freeman, Laura E Beane, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brenner, Hermann, Brucker, Sara Y, Buys, Saundra S, Castelao, Jose E, Chan, Tsun L, Chang-Claude, Jenny, Chanock, Stephen J, Choi, Ji-Yeob, Chung, Wendy K, Colonna, Sarah V, Cornelissen, Sten, Couch, Fergus J, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Yu-Tang, García-Closas, Montserrat, García-Sáenz, José A, Genkinger, Jeanine, Gentry-Maharaj, Aleksandra, Grassmann, Felix, Guénel, Pascal, Gündert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Harkness, Elaine F, Harrington, Patricia A, Hartikainen, Jaana M, Hartman, Mikael, Hein, Alexander, Ho, Weang-Kee, Hooning, Maartje J, Hoppe, Reiner, Hopper, John L, Houlston, Richard S, Howell, Anthony, Hunter, David J, Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K, Kim, Sung-Won, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, Kwong, Ava, Lacey, James V, Lambrechts, Diether, and Le Marchand, Loic
Subjects: Breast Cancer, Genetics, Clinical Research, Cancer, Aetiology, 2.1 Biological and endogenous factors, Humans, Female, Breast Neoplasms, Genetic Predisposition to Disease, Black People, Genetic Testing, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Formins, Breast cancer susceptibility, Diverse ancestry, Rare variants, Gene regulation, Genome-wide association study, NBCS Collaborators, CTS Consortium, ABCTB Investigators, Clinical Sciences
Abstract: BackgroundLow-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.MethodsWe evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.ResultsIn European ancestry samples, 14 genes were significantly associated (q
Published: 2023

5. Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

Author: Dixon-Suen, Suzanne C, Lewis, Sarah J, Martin, Richard M, English, Dallas R, Boyle, Terry, Giles, Graham G, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Lush, Michael, Investigators, ABCTB, Ahearn, Thomas U, Ambrosone, Christine B, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Auvinen, Päivi, Freeman, Laura E Beane, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brenner, Hermann, Brüning, Thomas, Buys, Saundra S, Camp, Nicola J, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Cessna, Melissa H, Chang-Claude, Jenny, Chanock, Stephen J, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Goldberg, Mark S, Guénel, Pascal, Gündert, Melanie, Hahnen, Eric, Haiman, Christopher A, Häberle, Lothar, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hart, Steven N, Harvie, Michelle, Hillemanns, Peter, Hollestelle, Antoinette, Hooning, Maartje J, Hoppe, Reiner, Hopper, John, Howell, Anthony, Hunter, David J, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, Lacey, James V, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Loibl, Sibylle, Lubiński, Jan, Mannermaa, Arto, and Manoochehri, Mehdi
Subjects: Aging, Genetics, Breast Cancer, Clinical Research, Cancer, Prevention, Female, Humans, Breast Neoplasms, Exercise, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, Sedentary Behavior, Breast Cancer Association Consortium, Breast, Physical activity, Sedentary Behaviour, Engineering, Medical and Health Sciences, Education, Sport Sciences
Abstract: ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
Published: 2022

6. Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O, Tyrer, Jonathan P, Barnes, Daniel R, Jones, Michelle R, Yang, Xin, Aben, Katja KH, Adank, Muriel A, Agata, Simona, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Aravantinos, Gerasimos, Arun, Banu K, Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Bjorge, Line, Black, Amanda, Bogdanova, Natalia V, Bonanni, Bernardo, Borg, Ake, Brenton, James D, Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S, Cai, Hui, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah, Cook, Linda S, Couch, Fergus J, Daly, Mary B, Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A, Domchek, Susan M, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M, Eliassen, Heather A, Engel, Christoph, Evans, Gareth D, Fasching, Peter A, Flanagan, James M, Fortner, Renée T, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Gensini, Francesca, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas VO, Harris, Holly R, Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Estrid, Høgdall, Claus K, Hopper, John L, Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul A, and Janavicius, Ramunas
Subjects: GEMO Study Collaborators, GC-HBOC Study Collaborators, EMBRACE Collaborators, OPAL Study Group, AOCS Group, KConFab Investigators, HEBON Investigators, OCAC Consortium, CIMBA Consortium, Genetics, Clinical Sciences, Genetics & Heredity
Published: 2022

7. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author: Dareng, Eileen O, Tyrer, Jonathan P, Barnes, Daniel R, Jones, Michelle R, Yang, Xin, Aben, Katja KH, Adank, Muriel A, Agata, Simona, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Aravantinos, Gerasimos, Arun, Banu K, Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Bjorge, Line, Black, Amanda, Bogdanova, Natalia V, Bonanni, Bernardo, Borg, Ake, Brenton, James D, Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S, Cai, Hui, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah, Cook, Linda S, Couch, Fergus J, Daly, Mary B, Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A, Domchek, Susan M, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M, Eliassen, Heather A, Engel, Christoph, Evans, Gareth D, Fasching, Peter A, Flanagan, James M, Fortner, Renée T, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Gensini, Francesca, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas VO, Harris, Holly R, Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Estrid, Høgdall, Claus K, Hopper, John L, Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul A, and Janavicius, Ramunas
Subjects: Prevention, Cancer, Ovarian Cancer, Rare Diseases, Good Health and Well Being, Bayes Theorem, Breast Neoplasms, Carcinoma, Ovarian Epithelial, Female, Genetic Predisposition to Disease, Humans, Male, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, GEMO Study Collaborators, GC-HBOC Study Collaborators, EMBRACE Collaborators, OPAL Study Group, AOCS Group, KConFab Investigators, HEBON Investigators, OCAC Consortium, CIMBA Consortium, Genetics, Clinical Sciences, Genetics & Heredity
Abstract: Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
Published: 2022

8. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Ahearn, Thomas U, Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L, Bolla, Manjeet K, Dennis, Joe, Dunning, Alison M, Lush, Michael, Wang, Qin, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Collée, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N, Krüger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W, Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G, Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, and McLean, Catriona
Subjects: Human Genome, Cancer, Genetics, Clinical Research, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Biomarkers, Tumor, Breast Neoplasms, Female, Genome-Wide Association Study, Humans, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Risk, Breast cancer, Etiologic heterogeneity, Genetic predisposition, Common breast cancer susceptibility variants, NBCS Collaborators, ABCTB Investigators, kConFab/AOCS Investigators, Receptor, erbB-2, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate
Published: 2022

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

Author: Dennis, Joe, Tyrer, Jonathan P, Walker, Logan C, Michailidou, Kyriaki, Dorling, Leila, Bolla, Manjeet K, Wang, Qin, 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, Collée, J Margriet, 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, 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, Kristensen, Vessela N, 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, and Soucy, Penny
Subjects: Human Genome, Breast Cancer, Genetics, Clinical Research, Cancer, Prevention, 2.1 Biological and endogenous factors, Aetiology, Breast Neoplasms, Case-Control Studies, DNA Copy Number Variations, Female, Genome, Human, Genome-Wide Association Study, Germ Cells, Humans, Risk Factors, NBCS Collaborators, CTS Consortium, ABCTB Investigators, kConFab/AOCS Investigators
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
Published: 2022

10. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author: Park, Hanla A, Neumeyer, Sonja, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baten, Adinda, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Fritschi, Lin, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Grip, Mervi, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny, Harkness, Elaine F, Hart, Steven N, He, Wei, Heemskerk-Gerritsen, Bernadette AM, Hopper, John L, Hunter, David J, Jager, Agnes, Jakubowska, Anna, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Koppert, Linetta B, Koutros, Stella, Kristensen, Vessela N, Kurian, Allison W, Lacey, James, Lambrechts, Diether, Le Marchand, Loic, Lo, Wing-Yee, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L, Muranen, Taru A, and Nevanlinna, Heli
Subjects: Genetics, Cancer, Substance Misuse, Clinical Research, Human Genome, Prevention, Drug Abuse (NIDA only), Breast Cancer, Tobacco, Tobacco Smoke and Health, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Breast Neoplasms, Case-Control Studies, Cigarette Smoking, Female, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, NBCS Collaborators, ABCTB Investigators, kConFab Investigators, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract: BackgroundDespite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.MethodsWe applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.ResultsGenetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.ConclusionOur MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
Published: 2021

11. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.

Author: Escala-Garcia, Maria, Canisius, Sander, Keeman, Renske, Beesley, Jonathan, Anton-Culver, Hoda, Arndt, Volker, Augustinsson, Annelie, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Bermisheva, Marina, Bojesen, Stig E, Bolla, Manjeet K, Brenner, Hermann, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Couch, Fergus J, Czene, Kamila, Daly, Mary B, Dennis, Joe, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Easton, Douglas F, Ekici, Arif B, Eliassen, A Heather, Fasching, Peter A, Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Geisler, Jürgen, Giles, Graham G, Grip, Mervi, Gündert, Melanie, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hartikainen, Jaana M, Heemskerk-Gerritsen, Bernadette AM, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L, Hunter, David J, Jacot, William, Jakubowska, Anna, John, Esther M, Jung, Audrey Y, Kaaks, Rudolf, Khusnutdinova, Elza, Koppert, Linetta B, Kraft, Peter, Kristensen, Vessela N, Kurian, Allison W, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Luben, Robert N, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Muranen, Taru A, Nevanlinna, Heli, Olshan, Andrew F, Olsson, Håkan, Park-Simon, Tjoung-Won, Patel, Alpa V, Peterlongo, Paolo, Pharoah, Paul DP, Punie, Kevin, Radice, Paolo, Rennert, Gad, Rennert, Hedy S, Romero, Atocha, Roylance, Rebecca, Rüdiger, Thomas, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J, Schmutzler, Rita K, Schoemaker, Minouk J, Scott, Christopher, Southey, Melissa C, Surowy, Harald, Swerdlow, Anthony J, Tamimi, Rulla M, Teras, Lauren R, Thomas, Emilie, Tomlinson, Ian, Troester, Melissa A, Vachon, Celine M, Wang, Qin, Winqvist, Robert, and Wolk, Alicja
Subjects: kConFab/AOCS Investigators, Cancer, Genetics, Breast Cancer, Prevention, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies
Abstract: Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10-8 and 4.42 × 10-8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
Published: 2021

12. FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women

Author: Figlioli, Gisella, Billaud, Amandine, Ahearn, Thomas U., Antonenkova, Natalia N., Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blok, Marinus J., Bogdanova, Natalia V., Bonanni, Bernardo, Burwinkel, Barbara, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Cessna, Melissa H., Chanock, Stephen J., Czene, Kamila, Devilee, Peter, Dörk, Thilo, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A., Figueroa, Jonine D., Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, González-Neira, Anna, Grassmann, Felix, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harrington, Patricia A., He, Wei, Hillemanns, Peter, Hollestelle, Antoinette, Hooning, Maartje J., Hoppe, Reiner, Howell, Anthony, Humphreys, Keith, Jager, Agnes, Jakubowska, Anna, Khusnutdinova, Elza K., Ko, Yon-Dschun, Kristensen, Vessela N., Lindblom, Annika, Lissowska, Jolanta, Lubiński, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Mavroudis, Dimitrios, Newman, William G., Obi, Nadia, Panayiotidis, Mihalis I., Rashid, Muhammad U., Rhenius, Valerie, Rookus, Matti A., Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sironen, Reijo, Southey, Melissa C., Suvanto, Maija, Tollenaar, Rob A. E. M., Tomlinson, Ian, Truong, Thérèse, van der Kolk, Lizet E., van Veen, Elke M., Wappenschmidt, Barbara, Yang, Xiaohong R., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Easton, Douglas F., Lush, Michael, Michailidou, Kyriaki, Pharoah, Paul D. P., Wang, Qin, Adank, Muriel A., Schmidt, Marjanka K., Andrulis, Irene L., Chang-Claude, Jenny, Nevanlinna, Heli, Chenevix-Trench, Georgia, Evans, D. Gareth, Milne, Roger L., Radice, Paolo, and Peterlongo, Paolo
Published: 2023
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13. Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

Author: Baxter, Joseph S, Johnson, Nichola, Tomczyk, Katarzyna, Gillespie, Andrea, Maguire, Sarah, Brough, Rachel, Fachal, Laura, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Brenner, Hermann, Brucker, Sara Y, Cai, Qiuyin, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chan, Tsun L, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Choi, Ji-Yeob, Clarke, Christine L, Collaborators, NBCS, Colonna, Sarah, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dossus, Laure, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Engel, Christoph, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Gago-Dominguez, Manuela, Gao, Chi, García-Closas, Montserrat, García-Sáenz, José A, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Guénel, Pascal, Gündert, Melanie, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hartman, Mikael, Hatse, Sigrid, Hauke, Jan, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L, Hou, Ming-Feng, Investigators, kConFab, Investigators, ABCTB, Ito, Hidemi, Iwasaki, Motoki, Jager, Agnes, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Joseph, Vijai, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kosma, Veli-Matti, Kraft, Peter, Kristensen, Vessela N, Kubelka-Sabit, Katerina, Kurian, Allison W, Kwong, Ava, and Lacey, James V
Subjects: Human Genome, Genetics, Cancer, Estrogen, Prevention, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Breast Neoplasms, CRISPR-Cas Systems, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 2, Female, Genetic Association Studies, Genetic Variation, Humans, Insulin-Like Growth Factor Binding Protein 5, Molecular Sequence Annotation, Promoter Regions, Genetic, Risk Factors, Sequence Deletion, NBCS Collaborators, kConFab Investigators, ABCTB Investigators, breast cancer risk, functional annotation, risk locus, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
Published: 2021

14. Author Correction: 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 BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, 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 BL, Hollestelle, Antoinette, and Hopper, John L
Subjects: GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Cancer
Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.
Published: 2021

15. 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, Heiko, 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 BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, 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 BL, Hollestelle, Antoinette, and Hopper, John L
Subjects: GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Risk Factors, Genotype, Linkage Disequilibrium, Mutation, Polymorphism, Single Nucleotide, Alleles, Quantitative Trait Loci, Adult, Middle Aged, Female, Genome-Wide Association Study, Breast Cancer, Prevention, Cancer, Genetic Testing, Human Genome, Genetics, 2.1 Biological and endogenous factors
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
Published: 2021

16. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Author: Johnson, Nichola, Maguire, Sarah, Morra, Anna, Kapoor, Pooja Middha, Tomczyk, Katarzyna, Jones, Michael E, Schoemaker, Minouk J, Gilham, Clare, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baynes, Caroline, Freeman, Laura E Beane, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dörk, Thilo, Eliassen, A Heather, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A, Hart, Steven N, Hooning, Maartje J, Hopper, John L, Howell, Anthony, Hunter, David J, Jager, Agnes, Jakubowska, Anna, John, Esther M, Kaaks, Rudolf, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kurian, Allison W, Lambrechts, Diether, Le Marchand, Loic, Linet, Martha, Lubiński, Jan, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John WM, Mavroudis, Dimitrios, Mayes, Rebecca, Meindl, Alfons, Milne, Roger L, Neuhausen, Susan L, Nevanlinna, Heli, Newman, William G, Nielsen, Sune F, Nordestgaard, Børge G, Obi, Nadia, Olshan, Andrew F, and Olson, Janet E
Subjects: Estrogen, Human Genome, Clinical Research, Cancer, Aging, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Alleles, Breast Neoplasms, Case-Control Studies, Cytochrome P-450 CYP3A, Estrone, Female, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Pregnanediol, Premenopause, Progesterone, Receptors, Estrogen, Receptors, Progesterone, NBCS Collaborators, AOCS Group, ABCTB Investigators, kConFab Investigators, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract: BackgroundEpidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.MethodsWe carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.ResultsFor pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8).ConclusionsThe CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
Published: 2021

17. Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women

Author: Dorling, Leila, Carvalho, Sara, Allen, Jamie, González-Neira, Anna, Luccarini, Craig, Wahlström, Cecilia, Pooley, Karen A, Parsons, Michael T, Fortuno, Cristina, Wang, Qin, Bolla, Manjeet K, Dennis, Joe, Keeman, Renske, Alonso, M Rosario, Álvarez, Nuria, Herraez, Belen, Fernandez, Victoria, Núñez-Torres, Rocio, Osorio, Ana, Valcich, Jeanette, Li, Minerva, Törngren, Therese, Harrington, Patricia A, Baynes, Caroline, Conroy, Don M, Decker, Brennan, Fachal, Laura, Mavaddat, Nasim, Ahearn, Thomas, Aittomäki, Kristiina, Antonenkova, Natalia N, Arnold, Norbert, Arveux, Patrick, Ausems, Margreet GEM, Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Bermisheva, Marina, Białkowska, Katarzyna, Blomqvist, Carl, Bogdanova, Natalia V, Bogdanova-Markov, Nadja, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Bremer, Michael, Briceno, Ignacio, Brüning, Thomas, Burwinkel, Barbara, Cameron, David A, Camp, Nicola J, Campbell, Archie, Carracedo, Angel, Castelao, Jose E, Cessna, Melissa H, Chanock, Stephen J, Christiansen, Hans, Collée, J Margriet, Cordina-Duverger, Emilie, Cornelissen, Sten, Czene, Kamila, Dörk, Thilo, Ekici, Arif B, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Försti, Asta, Gabrielson, Marike, Gago-Dominguez, Manuela, Georgoulias, Vassilios, Gil, Fabian, Giles, Graham G, Glendon, Gord, Garcia, Encarna B Gómez, Alnæs, Grethe I Grenaker, Guénel, Pascal, Hadjisavvas, Andreas, Haeberle, Lothar, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F, Hartikainen, Jaana M, Hartman, Mikael, He, Wei, Heemskerk-Gerritsen, Bernadette AM, Hillemanns, Peter, Hogervorst, Frans BL, Hollestelle, Antoinette, Ho, Weang Kee, Hooning, Maartje J, Howell, Anthony, Humphreys, Keith, Idris, Faiza, Jakubowska, Anna, and Jung, Audrey
Subjects: Breast Cancer, Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Logistic Models, Middle Aged, Mutation, Missense, Odds Ratio, Risk, Sequence Analysis, DNA, Young Adult, Breast Cancer Association Consortium, Medical and Health Sciences, General & Internal Medicine
Abstract: BackgroundGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.MethodsWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.ResultsProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.ConclusionsThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).
Published: 2021

18. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers

Author: Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise A, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, May, Taymaa, McAlpine, Jessica N, and McGuire, Valerie
Subjects: Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Human Genome, Uterine Cancer, Genetics, Biotechnology, Ovarian Cancer, Prevention, Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Endometrial Neoplasms, Female, Genome-Wide Association Study, Humans, Ovarian Neoplasms, Quantitative Trait Loci, Risk Factors, OPAL Study Group, AOCS Group, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundAccumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.MethodsUsing LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.ResultsGenetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.ConclusionsUsing cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.ImpactOur research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Published: 2021

19. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Author: Kramer, Iris, Hooning, Maartje J, Mavaddat, Nasim, Hauptmann, Michael, Keeman, Renske, Steyerberg, Ewout W, Giardiello, Daniele, Antoniou, Antonis C, Pharoah, Paul DP, Canisius, Sander, Abu-Ful, Zumuruda, Andrulis, Irene L, Anton-Culver, Hoda, Aronson, Kristan J, Augustinsson, Annelie, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Bremer, Michael, Brucker, Sara Y, Burwinkel, Barbara, Castelao, Jose E, Chan, Tsun L, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Choi, Ji-Yeob, Clarke, Christine L, Collée, J Margriet, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Giles, Graham G, Goldgar, David E, González-Neira, Anna, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette AM, Hollestelle, Antoinette, Hopper, John L, Hou, Ming-Feng, Howell, Anthony, Ito, Hidemi, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kang, Daehee, Kets, C Marleen, Khusnutdinova, Elza, Ko, Yon-Dschun, Kristensen, Vessela N, Kurian, Allison W, Kwong, Ava, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Meindl, Alfons, Milne, Roger, Mulligan, Anna Marie, Muranen, Taru A, Neuhausen, Susan L, Nevanlinna, Heli, Newman, William G, Olshan, Andrew F, Olson, Janet E, Olsson, Håkan, Park-Simon, Tjoung-Won, and Peto, Julian
Subjects: Breast Cancer, Prevention, Cancer, Adult, Aged, Asian People, Breast Neoplasms, Cohort Studies, Estrogen Receptor alpha, Female, Gene Expression, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Middle Aged, Multifactorial Inheritance, Neoadjuvant Therapy, Neoplasms, Second Primary, Prognosis, Proportional Hazards Models, Receptor, ErbB-2, Receptors, Progesterone, Risk Assessment, White People, NBCS Collaborators, ABCTB Investigators, kConFab Investigators, Receptor, erbB-2, contralateral breast cancer, epidemiology, genetic, polygenic risk score, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
Published: 2020

20. Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status

Author: Feng, Helian, Gusev, Alexander, Pasaniuc, Bogdan, Wu, Lang, Long, Jirong, Abu‐full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L, Anton‐Culver, Hoda, Antoniou, Antonis C, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Auer, Paul L, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canisius, Sander, Campa, Daniele, Carter, Brian D, Carter, Jonathan, Castelao, Jose E, Chang‐Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, De Leeneer, Kim, Dennis, Joe, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, dos‐Santos‐Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García‐Closas, Montserrat, García‐Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González‐Neira, Anna, and Greene, Mark H
Subjects: Biological Sciences, Health Sciences, Genetics, Cancer, Biotechnology, Prevention, Clinical Research, Human Genome, Estrogen, Breast Cancer, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Estrogens, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Receptors, Estrogen, Risk Assessment, Transcriptome, Vesicular Transport Proteins, breast cancer subtype, causal gene, GWAS, TWAS, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, Public Health and Health Services, Epidemiology
Abstract: Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
Published: 2020

21. Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

Author: Liu, Jingjing, Prager-van der Smissen, Wendy JC, Collée, J Margriet, Bolla, Manjeet K, Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Ahearn, Thomas U, Aittomäki, Kristiina, Ambrosone, Christine B, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Augustinsson, Annelie, Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Bermisheva, Marina, Bernstein, Leslie, Bogdanova, Natalia V, Bogdanova-Markov, Nadja, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Cai, Hui, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Choi, Ji-Yeob, Christiaens, Melissa, Clarke, Christine L, NBCS Collaborators, Couch, Fergus J, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, Guénel, Pascal, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Harrington, Patricia A, Hart, Steven N, Hartman, Mikael, Hillemanns, Peter, Hopper, John L, Hou, Ming-Feng, Hunter, David J, Huo, Dezheng, ABCTB Investigators, Ito, Hidemi, Iwasaki, Motoki, Jakimovska, Milena, Jakubowska, Anna, John, Esther M, Kaaks, Rudolf, Kang, Daehee, Keeman, Renske, Khusnutdinova, Elza, Kim, Sung-Won, Kraft, Peter, Kristensen, Vessela N, Kurian, Allison W, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Luben, Robert N, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, and Mariapun, Shivaani
Subjects: NBCS Collaborators, ABCTB Investigators
Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
Published: 2020

22. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Author: Zhang, Haoyu, Ahearn, Thomas U, Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Jiang, Xia, O'Mara, Tracy A, Zhao, Ni, Bolla, Manjeet K, Dunning, Alison M, Dennis, Joe, Wang, Qin, Ful, Zumuruda Abu, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Auer, Paul L, Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byers, Helen, Caldés, Trinidad, Caligo, Maria A, Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, Cornelissen, Sten, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M, Garber, Judy, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Häberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Hake, Christopher R, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, and Hillemanns, Peter
Subjects: kConFab Investigators, ABCTB Investigators, EMBRACE Study, GEMO Study Collaborators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, Case-Control Studies, Linkage Disequilibrium, Mutation, Female, Genome-Wide Association Study, Triple Negative Breast Neoplasms, Human Genome, Cancer, Prevention, Genetics, Breast Cancer, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P
Published: 2020

23. Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers

Author: Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Group, OPAL Study, Group, AOCS, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant B, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, and May, Taymaa
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Statistics, Mathematical Sciences, Oncology and Carcinogenesis, Aging, Rare Diseases, Human Genome, Cancer, Uterine Cancer, Ovarian Cancer, Prevention, Biotechnology, Aetiology, 2.1 Biological and endogenous factors
Abstract: Abstract: Accumulating evidence suggests a relationship between endometrial cancer and epithelial ovarian cancer. For example, endometrial cancer and epithelial ovarian cancer share epidemiological risk factors and molecular features observed across histotypes are held in common (e.g. serous, endometrioid and clear cell). Independent genome-wide association studies (GWAS) for endometrial cancer and epithelial ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. Using GWAS summary statistics, we explored the shared genetic etiology between endometrial cancer and epithelial ovarian cancer. Genetic correlation analysis using LD Score regression revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses by stratified by subtype. We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified at a sub-genome wide threshold (P < 5 × 10−7). Integration with promoter-associated HiChIP chromatin loops from immortalized endometrium and epithelial ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation.
Published: 2020

24. A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Author: Escala-Garcia, Maria, Abraham, Jean, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Ashworth, Alan, Auer, Paul L, Auvinen, Päivi, Beckmann, Matthias W, Beesley, Jonathan, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y, Burwinkel, Barbara, Caldas, Carlos, Canzian, Federico, Chang-Claude, Jenny, Chanock, Stephen J, Chin, Suet-Feung, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Dennis, Joe, Devilee, Peter, Dunn, Janet A, Dunning, Alison M, Dwek, Miriam, Earl, Helena M, Eccles, Diana M, Eliassen, A Heather, Ellberg, Carolina, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, George, Angela, Giles, Graham G, Goldgar, David E, González-Neira, Anna, Grip, Mervi, Guénel, Pascal, Guo, Qi, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Harrington, Patricia A, Hiller, Louise, Hooning, Maartje J, Hopper, John L, Howell, Anthony, Huang, Chiun-Sheng, Huang, Guanmengqian, Hunter, David J, Jakubowska, Anna, John, Esther M, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Kitahara, Cari M, Koppert, Linetta B, Kraft, Peter, Kristensen, Vessela N, Lambrechts, Diether, Le Marchand, Loic, Lejbkowicz, Flavio, Lindblom, Annika, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Maurer, Tabea, Mavroudis, Dimitrios, Meindl, Alfons, Milne, Roger L, Mulligan, Anna Marie, Neuhausen, Susan L, Nevanlinna, Heli, Newman, William G, Olshan, Andrew F, Olson, Janet E, and Olsson, Håkan
Subjects: Germ Cells, Humans, Breast Neoplasms, GTP-Binding Protein alpha Subunits, GTP-Binding Protein alpha Subunits, Gq-G11, Receptors, Estrogen, Prognosis, Computational Biology, Signal Transduction, Apoptosis, Genotype, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Circadian Clocks, Gq-G11, Receptors, Estrogen, Cancer, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies
Abstract: Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
Published: 2020

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

Author: Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Allen, Jamie, Kar, Siddhartha, Pooley, Karen A, Dennis, Joe, Michailidou, Kyriaki, Turman, Constance, Soucy, Penny, Lemaçon, Audrey, Lush, Michael, Tyrer, Jonathan P, Ghoussaini, Maya, Moradi Marjaneh, Mahdi, Jiang, Xia, Agata, Simona, Aittomäki, Kristiina, Alonso, M Rosario, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Auber, Bernd, Auer, Paul L, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Amie M, Blomqvist, Carl, Blot, William, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Borg, Ake, Bosse, Kristin, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brock, Ian W, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Camp, Nicola J, Campbell, Ian, Canzian, Federico, Carroll, Jason S, Carter, Brian D, Castelao, Jose E, Chiquette, Jocelyne, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, Collée, J Margriet, Cornelissen, Sten, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian S, Domchek, Susan M, Dörk, Thilo, Dos-Santos-Silva, Isabel, Droit, Arnaud, Dubois, Stéphane, Dumont, Martine, Duran, Mercedes, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Floris, Giuseppe, and Flyger, Henrik
Subjects: GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Bayes Theorem, Risk Factors, Chromosome Mapping, Regulatory Sequences, Nucleic Acid, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Female, Genome-Wide Association Study, Biomarkers, Tumor, Genetic Testing, Prevention, Genetics, Cancer, Breast Cancer, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
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.
Published: 2020

26. Two truncating variants in FANCC and breast cancer risk.

Author: Dörk, Thilo, Peterlongo, Paolo, Mannermaa, Arto, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Freeman, Laura E Beane, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Behrens, Sabine, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Canzian, Federico, Chan, Tsun L, Chang-Claude, Jenny, Chanock, Stephen J, Choi, Ji-Yeob, Christiansen, Hans, Clarke, Christine L, Couch, Fergus J, Czene, Kamila, Daly, Mary B, Dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gao, Chi, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, Guénel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hartman, Mikael, Hauke, Jan, Hein, Alexander, Hillemanns, Peter, Hogervorst, Frans BL, Hooning, Maartje J, Hopper, John L, Howell, Tony, Huo, Dezheng, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Khusnutdinova, Elza, Kim, Sung-Won, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Kwong, Ava, Lambrechts, Diether, Marchand, Loic Le, Li, Jingmei, Lindström, Sara, Linet, Martha, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Lubiński, Jan, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Elena, Matsuo, Keitaro, Mavroudis, Dimitris, and Meindl, Alfons
Subjects: ABCTB Investigators, NBCS Collaborators, Humans, Breast Neoplasms, Fanconi Anemia, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Case-Control Studies, Sequence Deletion, Female, Fanconi Anemia Complementation Group C Protein, Genetic Variation, Clinical Research, Breast Cancer, Genetics, Cancer, 2.1 Biological and endogenous factors, Biochemistry and Cell Biology, Other Physical Sciences
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

27. Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

Author: Shu, Xiang, Wu, Lang, Khankari, Nikhil K, Shu, Xiao-Ou, Wang, Thomas J, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Milne, Roger L, Schmidt, Marjanka K, Pharoah, Paul DP, Andrulis, Irene L, Hunter, David J, Simard, Jacques, Easton, Douglas F, Zheng, Wei, Alicia, Beeghly-Fadiel J, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Barrdahl, Myrto, Baynes, Caroline, Beane Freeman, Laura E, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldés, Trinidad, Canzian, Federico, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chenevix-Trench, Georgia, David Cheng, Ting-Yuan, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, David G, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Doheny, Kimberly F, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dunning, Alison M, Dwek, Miriam, Earp, H Shelton, Eccles, Diana M, Heather Eliassen, A, Engel, Christoph, Eriksson, Mikael, Gareth Evans, D, Fachal, Laura, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, He, Wei, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hogervorst, Frans B, Hollestelle, Antoinette, and Hoover, Robert N
Subjects: Clinical Research, Diabetes, Prevention, Nutrition, Obesity, Cancer, Aging, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Aged, Blood Glucose, Body Mass Index, Breast Neoplasms, Diabetes Mellitus, Type 2, Female, Humans, Insulin, Mendelian Randomization Analysis, Middle Aged, Obesity, Abdominal, Waist-Hip Ratio, Breast cancer, insulin, glucose, obesity, genetics, Mendelian randomization analysis, Breast Cancer Association Consortium, Statistics, Public Health and Health Services, Epidemiology
Abstract: BackgroundIn addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear.MethodsWe conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium.ResultsAll sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 × 10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 × 10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 × 10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 × 10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer.ConclusionsWe confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
Published: 2019

28. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Author: Ferreira, Manuel A, Gamazon, Eric R, Al-Ejeh, Fares, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Azzollini, Jacopo, Balmaña, Judith, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Broeks, Annegien, Burwinkel, Barbara, Caldés, Trinidad, Caligo, Maria A, Campa, Daniele, Campbell, Ian, Canzian, Federico, Carter, Jonathan, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Dennis, Joe, Devilee, Peter, Diez, Orland, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Friedman, Eitan, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, He, Wei, Heyworth, Jane, Hogervorst, Frans BL, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, Hulick, Peter J, Humphreys, Keith, Imyanitov, Evgeny N, ABCTB Investigators, HEBON Investigators, and BCFR Investigators
Subjects: EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Gene Expression Profiling, Quantitative Trait Loci, Female, Genome-Wide Association Study, Prevention, Cancer, Human Genome, Aging, Breast Cancer, Genetics, Biotechnology, 2.1 Biological and endogenous factors
Abstract: Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
Published: 2019

29. Genome-wide association study of germline variants and breast cancer-specific mortality.

Author: Escala-Garcia, Maria, Guo, Qi, Dörk, Thilo, Canisius, Sander, Keeman, Renske, Dennis, Joe, Beesley, Jonathan, Lecarpentier, Julie, Bolla, Manjeet K, Wang, Qin, Abraham, Jean, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Boeckx, Bram, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brentnall, Adam, Brinton, Louise, Broberg, Per, Brock, Ian W, Brucker, Sara Y, Burwinkel, Barbara, Caldas, Carlos, Caldés, Trinidad, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Chin, Suet-Feung, Clarke, Christine L, NBCS Collaborators, Cordina-Duverger, Emilie, Couch, Fergus J, Cox, David G, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dunn, Janet A, Dunning, Alison M, Durcan, Lorraine, Dwek, Miriam, Earl, Helena M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Galle, Eva, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, George, Angela, Georgoulias, Vassilios, Giles, Graham G, Glendon, Gord, Goldgar, David E, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan, Harkness, Elaine F, Harrington, Patricia A, Hart, Steven N, Hartikainen, Jaana M, Hein, Alexander, Hillemanns, Peter, Hiller, Louise, and Holleczek, Bernd
Subjects: NBCS Collaborators, Chromosomes, Human, Pair 7, Humans, Breast Neoplasms, Receptors, Estrogen, Prognosis, Proportional Hazards Models, Bayes Theorem, Female, Genetic Variation, Genome-Wide Association Study, White People, Genetics, Breast Cancer, Human Genome, Cancer, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract: BackgroundWe examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.MethodsMeta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).ResultsWe did not find any variant associated with breast cancer-specific mortality at P
Published: 2019

30. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Author: Mavaddat, Nasim, Michailidou, Kyriaki, Dennis, Joe, Lush, Michael, Fachal, Laura, Lee, Andrew, Tyrer, Jonathan P, Chen, Ting-Huei, Wang, Qin, Bolla, Manjeet K, Yang, Xin, Adank, Muriel A, Ahearn, Thomas, Aittomäki, Kristiina, Allen, Jamie, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Auvinen, Päivi, Barrdahl, Myrto, Beane Freeman, Laura E, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Bremer, Michael, Brenner, Hermann, Brentnall, Adam, Brock, Ian W, Brooks-Wilson, Angela, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Campa, Daniele, Carter, Brian D, Castelao, Jose E, Chanock, Stephen J, Chlebowski, Rowan, Christiansen, Hans, Clarke, Christine L, Collée, J Margriet, Cordina-Duverger, Emilie, Cornelissen, Sten, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Försti, Asta, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Georgoulias, Vassilios, Giles, Graham G, Gilyazova, Irina R, Glendon, Gord, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Grenaker Alnæs, Grethe I, Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, and Hankinson, Susan E
Subjects: ABCTB Investigators, kConFab/AOCS Investigators, NBCS Collaborators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Receptors, Estrogen, Medical History Taking, Risk Assessment, Reproducibility of Results, Age Factors, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, breast, cancer, epidemiology, genetic, polygenic, prediction, risk, score, screening, stratification, Human Genome, Cancer, Genetics, Clinical Research, Prevention, Breast Cancer, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
Published: 2019

31. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Author: Figlioli, Gisella, Bogliolo, Massimo, Catucci, Irene, Caleca, Laura, Lasheras, Sandra Viz, Pujol, Roser, Kiiski, Johanna I, Muranen, Taru A, Barnes, Daniel R, Dennis, Joe, Michailidou, Kyriaki, Bolla, Manjeet K, Leslie, Goska, Aalfs, Cora M, Adank, Muriel A, Adlard, Julian, Agata, Simona, Cadoo, Karen, Agnarsson, Bjarni A, Ahearn, Thomas, Aittomäki, Kristiina, Ambrosone, Christine B, Andrews, Lesley, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Auber, Bernd, Auvinen, Päivi, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Beane Freeman, Laura E, Beauparlant, Charles Joly, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Berger, Raanan, Bermisheva, Marina, Blanco, Amie M, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Anders, Bojesen, Stig E, Bonanni, Bernardo, Borg, Ake, Brady, Angela F, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A, Campa, Daniele, Campbell, Ian G, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Claes, Kathleen BM, Clarke, Christine L, Collavoli, Anita, Conner, Thomas A, Cox, David G, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian S, Ditsch, Nina, Domchek, Susan M, Dorfling, Cecilia M, dos-Santos-Silva, Isabel, Durda, Katarzyna, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Foulkes, William D, Friebel, Tara M, Friedman, Eitan, Gabrielson, Marike, Gaddam, Pragna, and Gago-Dominguez, Manuela
Subjects: Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Clinical Research, Genetics, Breast Cancer, Cancer, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, ABCTB Investigators, GEMO Study Collaborators, KConFab, Cancer genetics, Clinical sciences, Oncology and carcinogenesis, Epidemiology
Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
Published: 2019

32. Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Author: Dorling, Leila, Carvalho, Sara, Allen, Jamie, Parsons, Michael T., Fortuno, Cristina, González-Neira, Anna, Heijl, Stephan M., Adank, Muriel A., Ahearn, Thomas U., Andrulis, Irene L., Auvinen, Päivi, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V., Bojesen, Stig E., Bolla, Manjeet K., Bremer, Michael, Briceno, Ignacio, Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J. Margriet, Czene, Kamila, Dennis, Joe, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Giles, Graham G., Glendon, Gord, Guénel, Pascal, Gündert, Melanie, Hadjisavvas, Andreas, Hahnen, Eric, Hall, Per, Hamann, Ute, Harkness, Elaine F., Hartman, Mikael, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Jung, Audrey, Khusnutdinova, Elza, Kim, Sung-Won, Ko, Yon-Dschun, Kristensen, Vessela N., Lakeman, Inge M. M., Li, Jingmei, Lindblom, Annika, Loizidou, Maria A., Lophatananon, Artitaya, Lubiński, Jan, Luccarini, Craig, Madsen, Michael J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L., Mohd Taib, Nur Aishah, Muir, Kenneth, Nevanlinna, Heli, Newman, William G., Oosterwijk, Jan C., Park, Sue K., Peterlongo, Paolo, Radice, Paolo, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Shah, Mitul, Sim, Xueling, Southey, Melissa C., Surowy, Harald, Suvanto, Maija, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van Asperen, Christi J., Waltes, Regina, Wang, Qin, Yang, Xiaohong R., Pharoah, Paul D. P., Schmidt, Marjanka K., Benitez, Javier, Vroling, Bas, Dunning, Alison M., Teo, Soo Hwang, Kvist, Anders, de la Hoya, Miguel, Devilee, Peter, Spurdle, Amanda B., Vreeswijk, Maaike P. G., and Easton, Douglas F.
Published: 2022
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33. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author: Wu, Lang, Shi, Wei, Long, Jirong, Guo, Xingyi, Michailidou, Kyriaki, Beesley, Jonathan, Bolla, Manjeet K, Shu, Xiao-Ou, Lu, Yingchang, Cai, Qiuyin, Al-Ejeh, Fares, Rozali, Esdy, Wang, Qin, Dennis, Joe, Li, Bingshan, Zeng, Chenjie, Feng, Helian, Gusev, Alexander, Barfield, Richard T, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y, Burwinkel, Barbara, Caldés, Trinidad, Canzian, Federico, Carter, Brian D, Castelao, J Esteban, Chang-Claude, Jenny, Chen, Xiaoqing, Cheng, Ting-Yuan David, Christiansen, Hans, Clarke, Christine L, NBCS Collaborators, Collée, Margriet, Cornelissen, Sten, Couch, Fergus J, Cox, David, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Doheny, Kimberly F, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Eccles, Diana M, Eilber, Ursula, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Fachal, Laura, Fasching, Peter A, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, and Huang, Guanmengqian
Subjects: Biological Sciences, Genetics, Human Genome, Biotechnology, Prevention, Breast Cancer, Women's Health, Cancer Genomics, Cancer, 2.1 Biological and endogenous factors, Generic health relevance, Breast Neoplasms, Case-Control Studies, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk, Transcriptome, NBCS Collaborators, kConFab/AOCS Investigators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P
Published: 2018

34. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Author: Milne, Roger L, Kuchenbaecker, Karoline B, Michailidou, Kyriaki, Beesley, Jonathan, Kar, Siddhartha, Lindström, Sara, Hui, Shirley, Lemaçon, Audrey, Soucy, Penny, Dennis, Joe, Jiang, Xia, Rostamianfar, Asha, Finucane, Hilary, Bolla, Manjeet K, McGuffog, Lesley, Wang, Qin, Aalfs, Cora M, Adams, Marcia, Adlard, Julian, Agata, Simona, Ahmed, Shahana, Ahsan, Habibul, Aittomäki, Kristiina, Al-Ejeh, Fares, Allen, Jamie, Ambrosone, Christine B, Amos, Christopher I, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Auber, Bernd, Auer, Paul L, Ausems, Margreet GEM, Azzollini, Jacopo, Bacot, François, Balmaña, Judith, Barile, Monica, Barjhoux, Laure, Barkardottir, Rosa B, Barrdahl, Myrto, Barnes, Daniel, Barrowdale, Daniel, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Bignon, Yves-Jean, Blazer, Kathleen R, Blok, Marinus J, Blomqvist, Carl, Blot, William, Bobolis, Kristie, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Anders, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Bozsik, Aniko, Bradbury, Angela R, Brand, Judith S, Brauch, Hiltrud, Brenner, Hermann, Bressac-de Paillerets, Brigitte, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Brunet, Joan, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byun, Jinyoung, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canzian, Federico, Caron, Olivier, Carracedo, Angel, Carter, Brian D, Castelao, J Esteban, Castera, Laurent, Caux-Moncoutier, Virginie, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Xiaoqing, Cheng, Ting-Yuan David, Chiquette, Jocelyne, Christiansen, Hans, Claes, Kathleen BM, Clarke, Christine L, Conner, Thomas, Conroy, Don M, and Cook, Jackie
Subjects: Biological Sciences, Genetics, Cancer, Human Genome, Prevention, Breast Cancer, Aging, Estrogen, 2.1 Biological and endogenous factors, Aetiology, BRCA1 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Humans, Mutation, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors, White People, ABCTB Investigators, EMBRACE, GEMO Study Collaborators, HEBON, kConFab/AOCS Investigators, NBSC Collaborators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
Published: 2017

35. Association analysis identifies 65 new breast cancer risk loci

Author: Michailidou, Kyriaki, Lindström, Sara, Dennis, Joe, Beesley, Jonathan, Hui, Shirley, Kar, Siddhartha, Lemaçon, Audrey, Soucy, Penny, Glubb, Dylan, Rostamianfar, Asha, Bolla, Manjeet K, Wang, Qin, Tyrer, Jonathan, Dicks, Ed, Lee, Andrew, Wang, Zhaoming, Allen, Jamie, Keeman, Renske, Eilber, Ursula, French, Juliet D, Qing Chen, Xiao, Fachal, Laura, McCue, Karen, McCart Reed, Amy E, Ghoussaini, Maya, Carroll, Jason S, Jiang, Xia, Finucane, Hilary, Adams, Marcia, Adank, Muriel A, Ahsan, Habibul, Aittomäki, Kristiina, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Arun, Banu, Auer, Paul L, Bacot, François, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brand, Judith S, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brock, Ian W, Broeks, Annegien, Brooks-Wilson, Angela, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Butterbach, Katja, Cai, Qiuyin, Cai, Hui, Caldés, Trinidad, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chan, Tsun L, David Cheng, Ting-Yuan, Seng Chia, Kee, Choi, Ji-Yeob, Christiansen, Hans, Clarke, Christine L, Collée, Margriet, Conroy, Don M, Cordina-Duverger, Emilie, Cornelissen, Sten, Cox, David G, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Doheny, Kimberly F, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Elvira, Mingajeva, and Engel, Christoph
Subjects: Cancer, Asia, Asian People, Binding Sites, Breast Neoplasms, Computer Simulation, Europe, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Risk Assessment, Transcription Factors, White People, NBCS Collaborators, ABCTB Investigators, ConFab/AOCS Investigators, General Science & Technology
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P
Published: 2017

36. Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

Author: Muranen, Taru A, Greco, Dario, Blomqvist, Carl, Aittomäki, Kristiina, Khan, Sofia, Hogervorst, Frans, Verhoef, Senno, Pharoah, Paul DP, Dunning, Alison M, Shah, Mitul, Luben, Robert, Bojesen, Stig E, Nordestgaard, Børge G, Schoemaker, Minouk, Swerdlow, Anthony, García-Closas, Montserrat, Figueroa, Jonine, Dörk, Thilo, Bogdanova, Natalia V, Hall, Per, Li, Jingmei, Khusnutdinova, Elza, Bermisheva, Marina, Kristensen, Vessela, Borresen-Dale, Anne-Lise, Investigators, NBCS, Peto, Julian, dos Santos Silva, Isabel, Couch, Fergus J, Olson, Janet E, Hillemans, Peter, Park-Simon, Tjoung-Won, Brauch, Hiltrud, Hamann, Ute, Burwinkel, Barbara, Marme, Frederik, Meindl, Alfons, Schmutzler, Rita K, Cox, Angela, Cross, Simon S, Sawyer, Elinor J, Tomlinson, Ian, Lambrechts, Diether, Moisse, Matthieu, Lindblom, Annika, Margolin, Sara, Hollestelle, Antoinette, Martens, John WM, Fasching, Peter A, Beckmann, Matthias W, Andrulis, Irene L, Knight, Julia A, Investigators, kConFab AOCS, Anton-Culver, Hoda, Ziogas, Argyrios, Giles, Graham G, Milne, Roger L, Brenner, Hermann, Arndt, Volker, Mannermaa, Arto, Kosma, Veli-Matti, Chang-Claude, Jenny, Rudolph, Anja, Devilee, Peter, Seynaeve, Caroline, Hopper, John L, Southey, Melissa C, John, Esther M, Whittemore, Alice S, Bolla, Manjeet K, Wang, Qin, Michailidou, Kyriaki, Dennis, Joe, Easton, Douglas F, Schmidt, Marjanka K, and Nevanlinna, Heli
Subjects: Cancer, Prevention, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Breast Neoplasms, Checkpoint Kinase 2, Female, Genes, Modifier, Genetic Predisposition to Disease, Humans, Odds Ratio, Penetrance, Sequence Deletion, breast cancer, Breast Cancer Association Consortium, CHEK2*1100delC, common variants, polygenic risk score, NBCS Investigators, kConFab/AOCS Investigators, Genetics, Clinical Sciences, Genetics & Heredity
Abstract: PurposeCHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).MethodsUsing genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction.ResultsThe PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average.ConclusionOur results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.
Published: 2017

37. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

Author: Phelan, Catherine M, Kuchenbaecker, Karoline B, Tyrer, Jonathan P, Kar, Siddhartha P, Lawrenson, Kate, Winham, Stacey J, Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J, Chornokur, Ganna, Earp, Madalene A, Lyra, Paulo C, Lee, Janet M, Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Leslie, Goska, Aalfs, Cora M, Aben, Katja KH, Adams, Marcia, Adlard, Julian, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia, AOCS study group, Aravantinos, Gerasimos, Arnold, Norbert, Arun, Banu K, Arver, Brita, Azzollini, Jacopo, Balmaña, Judith, Banerjee, Susana N, Barjhoux, Laure, Barkardottir, Rosa B, Bean, Yukie, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Birrer, Michael J, Bjorge, Line, Black, Amanda, Blankstein, Kenneth, Blok, Marinus J, Bodelon, Clara, Bogdanova, Natalia, Bojesen, Anders, Bonanni, Bernardo, Borg, Åke, Bradbury, Angela R, Brenton, James D, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Bruinsma, Fiona, Brunet, Joan, Buecher, Bruno, Butzow, Ralf, Buys, Saundra S, Caldes, Trinidad, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Carney, Michael E, Cescon, Terence, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen, Chen, Xiao Qing, Chiew, Yoke-Eng, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen BM, Conner, Thomas, Cook, Linda S, Cook, Jackie, Cramer, Daniel W, Cunningham, Julie M, D'Aloisio, Aimee A, Daly, Mary B, Damiola, Francesca, Damirovna, Sakaeva Dina, Dansonka-Mieszkowska, Agnieszka, Dao, Fanny, Davidson, Rosemarie, DeFazio, Anna, Delnatte, Capucine, Doheny, Kimberly F, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer Anne, Domchek, Susan M, and Dorfling, Cecilia M
Subjects: AOCS study group, EMBRACE Study, GEMO Study Collaborators, HEBON Study, KConFab Investigators, OPAL study group, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Genetic Predisposition to Disease, Telomere-Binding Proteins, BRCA1 Protein, BRCA2 Protein, Risk Factors, Genotype, Mutation, Polymorphism, Single Nucleotide, Alleles, Female, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci, Carcinoma, Ovarian Epithelial, Genetics, Cancer, Human Genome, Rare Diseases, Prevention, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Published: 2017

38. Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

Author: Yiangou, Kristia, primary, Mavaddat, Nasim, additional, Dennis, Joe, additional, Zanti, Maria, additional, Wang, Qin, additional, Bolla, Manjeet K., additional, Abubakar, Mustapha, additional, Ahearn, Thomas U., additional, Andrulis, Irene L., additional, Anton-Culver, Hoda, additional, Antonenkova, Natalia N., additional, Arndt, Volker, additional, Aronson, Kristan J., additional, Augustinsson, Annelie, additional, Baten, Adinda, additional, Behrens, Sabine, additional, Bermisheva, Marina, additional, Berrington de Gonzalez, Amy, additional, Bialkowska, Katarzyna, additional, Boddicker, Nicholas, additional, Bodelon, Clara, additional, Bogdanova, Natalia V., additional, Bojesen, Stig E., additional, Brantley, Kristen D., additional, Brauch, Hiltrud, additional, Brenner, Hermann, additional, Camp, Nicola J., additional, Canzian, Federico, additional, Castelao, Jose E., additional, Cessna, Melissa H., additional, Chang-Claude, Jenny, additional, Chenevix-Trench, Georgia, additional, Chung, Wendy K., additional, Collaborators, NBCS, additional, Colonna, Sarah V., additional, Couch, Fergus J., additional, Cox, Angela, additional, Cross, Simon S., additional, Czene, Kamila, additional, Daly, Mary B., additional, Devilee, Peter, additional, Dork, Thilo, additional, Dunning, Alison M., additional, Eccles, Diana M., additional, Eliassen, A. Heather, additional, Engel, Christoph, additional, Eriksson, Mikael, additional, Evans, D. Gareth, additional, Fasching, Peter A., additional, Fletcher, Olivia, additional, Flyger, Henrik, additional, Fritschi, Lin, additional, Gago-Dominguez, Manuela, additional, Gentry-Maharaj, Aleksandra, additional, Gonzalez-Neira, Anna, additional, Guenel, Pascal, additional, Hahnen, Eric, additional, Haiman, Christopher A., additional, Hamann, Ute, additional, Hartikainen, Jaana M., additional, Ho, Vikki, additional, Hodge, James, additional, Hollestelle, Antoinette, additional, Honisch, Ellen, additional, Hooning, Maartje J., additional, Hoppe, Reiner, additional, Hopper, John L., additional, Howell, Sacha, additional, Howell, Anthony, additional, Investigators, ABCTB, additional, Investigators, kConFab, additional, Jakovchevska, Simona, additional, Jakubowska, Anna, additional, Jernstrom, Helena, additional, Johnson, Nichola, additional, Kaaks, Rudolf, additional, Khusnutdinova, Elza K., additional, Kitahara, Cari M., additional, Koutros, Stella, additional, Kristensen, Vessela N., additional, Lacey, James V., additional, Lambrechts, Diether, additional, Lejbkowicz, Flavio, additional, Lindblom, Annika, additional, Lush, Michael, additional, Mannermaa, Arto, additional, Mavroudis, Dimitrios, additional, Menon, Usha, additional, Murphy, Rachel A., additional, Nevanlinna, Heli, additional, Obi, Nadia, additional, Offit, Kenneth, additional, Park-Simon, Tjoung-Won, additional, Patel, Alpa V., additional, Peng, Cheng, additional, Peterlongo, Paolo, additional, Pita, Guillermo, additional, Plaseska-Karanfilska, Dijana, additional, Pylkas, Katri, additional, Radice, Paolo, additional, Rashid, Muhammad U., additional, Rennert, Gad, additional, Roberts, Eleanor, additional, Rodriguez, Juan, additional, Romero, Atocha, additional, Rosenberg, Efraim H., additional, Saloustros, Emmanouil, additional, Sandler, Dale P., additional, Sawyer, Elinor J., additional, Schmutzler, Rita K., additional, Scott, Christopher G., additional, Shu, Xiao-Ou, additional, Southey, Melissa C., additional, Stone, Jennifer, additional, Taylor, Jack A., additional, Teras, Lauren R., additional, van de Beek, Irma, additional, Willett, Walter, additional, Winqvist, Robert, additional, Zheng, Wei, additional, Vachon, Celine M., additional, Schmidt, Marjanka K., additional, Hall, Per, additional, MacInnis, Robert J., additional, Milne, Roger L., additional, Pharoah, Paul D.P., additional, Simard, Jacques, additional, Antoniou, Antonis C., additional, Easton, Douglas F., additional, and Michailidou, Kyriaki, additional
Published: 2024
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39. Age- and Tumor Subtype–Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

Author: Schmidt, Marjanka K, Hogervorst, Frans, van Hien, Richard, Cornelissen, Sten, Broeks, Annegien, Adank, Muriel A, Meijers, Hanne, Waisfisz, Quinten, Hollestelle, Antoinette, Schutte, Mieke, van den Ouweland, Ans, Hooning, Maartje, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Antoniou, Antonis C, Arndt, Volker, Bermisheva, Marina, Bogdanova, Natalia V, Bolla, Manjeet K, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dunning, Alison M, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Galle, Eva, García-Closas, Montserrat, Giles, Graham G, Haeberle, Lothar, Hall, Per, Hillemanns, Peter, Hopper, John L, Jakubowska, Anna, John, Esther M, Jones, Michael, Khusnutdinova, Elza, Knight, Julia A, Kosma, Veli-Matti, Kristensen, Vessela, Lee, Andrew, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Meindl, Alfons, Milne, Roger L, Muranen, Taru A, Newcomb, Polly A, Offit, Kenneth, Park-Simon, Tjoung-Won, Peto, Julian, Pharoah, Paul DP, Robson, Mark, Rudolph, Anja, Sawyer, Elinor J, Schmutzler, Rita K, Seynaeve, Caroline, Soens, Julie, Southey, Melissa C, Spurdle, Amanda B, Surowy, Harald, Swerdlow, Anthony, Tollenaar, Rob AEM, Tomlinson, Ian, Trentham-Dietz, Amy, Vachon, Celine, Wang, Qin, Whittemore, Alice S, Ziogas, Argyrios, van der Kolk, Lizet, Nevanlinna, Heli, Dörk, Thilo, Bojesen, Stig, and Easton, Douglas F
Subjects: Clinical Research, Genetics, Cancer, Breast Cancer, Aetiology, 2.1 Biological and endogenous factors, Adult, Age Factors, Aged, Aged, 80 and over, Breast Neoplasms, Case-Control Studies, Checkpoint Kinase 2, Female, Genetic Predisposition to Disease, Heterozygote, Homozygote, Humans, Middle Aged, Odds Ratio, Receptors, Estrogen, Receptors, Progesterone, Risk Assessment, Sequence Deletion, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: PurposeCHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC.Patients and methodsCHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies.ResultsProportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom.ConclusionThese CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up.
Published: 2016

40. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Author: Zeng, Chenjie, Guo, Xingyi, Long, Jirong, Kuchenbaecker, Karoline B, Droit, Arnaud, Michailidou, Kyriaki, Ghoussaini, Maya, Kar, Siddhartha, Freeman, Adam, Hopper, John L, Milne, Roger L, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Agata, Simona, Ahmed, Shahana, AittomÃ¤ki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arason, Adalgeir, Arndt, Volker, Arun, Banu K, Arver, Brita, Bacot, Francois, Barrowdale, Daniel, Baynes, Caroline, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Blot, William J, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith S, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, BrÃ¼ning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Carpenter, Jane, Chang-Claude, Jenny, Choi, Ji-Yeob, Claes, Kathleen B. M, Clarke, Christine, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, De Leeneer, Kim, Devilee, Peter, Diez, Orland, Domchek, Susan M, Doody, Michele, Dorfling, Cecilia M, DÃ¶rk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Dworniczak, Bernd, Egan, Kathleen, Eilber, Ursula, Einbeigi, Zakaria, Ejlertsen, Bent, Ellis, Steve, Frost, Debra, Lalloo, Fiona, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Friedlander, Michael, Friedman, Eitan, Gambino, Gaetana, Gao, Yu-Tang, Garber, Judy, GarcÃa-Closas, Montserrat, Gehrig, Andrea, Damiola, Francesca, Lesueur, Fabienne, Mazoyer, Sylvie, Stoppa-Lyonnet, Dominique, Giles, Graham G, Godwin, Andrew K, Goldgar, David E, GonzÃ¡lez-Neira, Anna, Greene, Mark H, GuÃ©nel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Hallberg, Emily, Hamann, Ute, and Hansen, Thomas V. O
Published: 2016

41. MicroRNA-200 family expression analysis in metastatic clear cell renal cell carcinoma patients

Author: Gilyazova, Irina R., Klimentova, Elizaveta A., Bulygin, Kirill V., Izmailov, Adel A., Bermisheva, Marina A., Galimova, Elmira F., Safiullin, Ruslan I., Galimov, Shamil N., Pavlov, Valentin N., and Khusnutdinova, Elsa K.
Published: 2020
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42. Exome sequencing study of Russian breast cancer patients suggests a predisposing role for USP39

Author: Kuligina, Ekaterina S., Sokolenko, Anna P., Bizin, Ilya V., Romanko, Alexandr A., Zagorodnev, Kirill A., Anisimova, Maria O., Krylova, Daria D., Anisimova, Elena I., Mantseva, Maria A., Varma, Ashok K., Hasan, Syed K., Ni, Valeria I., Koloskov, Andrey V., Suspitsin, Evgeny N., Venina, Aigul R., Aleksakhina, Svetlana N., Sokolova, Tatiana N., Milanović, Ana Marija, Schürmann, Peter, Prokofyeva, Darya S., Bermisheva, Marina A., Khusnutdinova, Elza K., Bogdanova, Natalia, Dörk, Thilo, and Imyanitov, Evgeny N.
Published: 2020
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43. Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset

Author: Sahlberg, Kristine K., Børresen-Dale, Anne-Lise, Gram, Inger Torhild, Olsen, Karina Standahl, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, OSBREAC, Grenaker Alnæs, Grethe I., Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, Dawson, Sarah-Jane, deFazio, Anna, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Edwards, Stacey, Farshid, Gelareh, Fellows, Andrew, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet, Friedlander, Michael, Gaff, Clara, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Hart, Stewart, Harraka, Philip, Hayward, Nick, Hopper, John, Hoskins, Cass, Hunt, Clare, Jenkins, Mark, Kidd, Alexa, Kirk, Judy, Koehler, Jessica, Kollias, James, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason, Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Lobb, Liz, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Meiser, Bettina, Nightingale, Sophie, O'Connell, Shona, O'Sullivan, Sarah, Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Pearn, Amy, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Saleh, Mona, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Savas, Peter, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta, Simpson, Peter, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, Alison, Tucker, Kathy, Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, Ingrid, Young, Mary Ann, Zaheed, Milita, Davidson, Aimee L., Michailidou, Kyriaki, Parsons, Michael T., Fortuno, Cristina, Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Naven, Marc, Abubakar, Mustapha, Ahearn, Thomas U., Alonso, M. Rosario, Andrulis, Irene L., Antoniou, Antonis C., Auvinen, Päivi, Behrens, Sabine, Bermisheva, Marina A., Bogdanova, Natalia V., Bojesen, Stig E., Brüning, Thomas, Byers, Helen J., Camp, Nicola J., Campbell, Archie, Castelao, Jose E., Cessna, Melissa H., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Collée, J. Margriet, Czene, Kamila, Dörk, Thilo, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine D., Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, Glendon, Gord, González-Neira, Anna, Grassmann, Felix, Gronwald, Jacek, Guénel, Pascal, Hadjisavvas, Andreas, Haeberle, Lothar, Hall, Per, Hamann, Ute, Hartman, Mikael, Ho, Peh Joo, Hooning, Maartje J., Hoppe, Reiner, Howell, Anthony, Jakubowska, Anna, Khusnutdinova, Elza K., Kristensen, Vessela N., Li, Jingmei, Lim, Joanna, Lindblom, Annika, Liu, Jenny, Lophatananon, Artitaya, Mannermaa, Arto, Mavroudis, Dimitrios A., Mensenkamp, Arjen R., Milne, Roger L., Muir, Kenneth R., Newman, William G., Obi, Nadia, Panayiotidis, Mihalis I., Park, Sue K., Park-Simon, Tjoung-Won, Peterlongo, Paolo, Radice, Paolo, Rashid, Muhammad U., Rhenius, Valerie, Saloustros, Emmanouil, Sawyer, Elinor J., Schmidt, Marjanka K., Seibold, Petra, Shah, Mitul, Southey, Melissa C., Teo, Soo Hwang, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van de Beek, Irma, van der Hout, Annemieke H., Wendt, Camilla C., Dunning, Alison M., Pharoah, Paul D.P., Devilee, Peter, Easton, Douglas F., James, Paul A., and Spurdle, Amanda B.
Published: 2024
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44. 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

Author: Warren, Helen, Dudbridge, Frank, Fletcher, Olivia, Orr, Nick, Johnson, Nichola, Hopper, John L, Apicella, Carmel, Southey, Melissa C, Mahmoodi, Maryam, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Braaf, Linda M, Muir, Kenneth R, Lophatananon, Artitaya, Chaiwerawattana, Arkom, Wiangnon, Surapon, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Schulz-Wendtland, Ruediger, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Guénel, Pascal, Truong, Thérèse, Laurent-Puig, Pierre, Mulot, Claire, Bojesen, Stig E, Nielsen, Sune F, Flyger, Henrik, Nordestgaard, Børge G, Milne, Roger L, Benítez, Javier, Arias-Pérez, José-Ignacio, Zamora, M Pilar, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Dur, Christina Clarke, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Langheinz, Anne, Meindl, Alfons, Golatta, Michael, Bartram, Claus R, Schmutzler, Rita K, Brauch, Hiltrud, Justenhoven, Christina, Brüning, Thomas, Network, for The GENICA, Chang-Claude, Jenny, Wang-Gohrke, Shan, Eilber, Ursula, Dörk, Thilo, Schürmann, Peter, Bremer, Michael, Hillemanns, Peter, Nevanlinna, Heli, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia, Antonenkova, Natalia, Rogov, Yuriy, Bermisheva, Marina, Prokofyeva, Darya, Zinnatullina, Guzel, Khusnutdinova, Elza, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Hartikainen, Jaana M, Kataja, Vesa, Chenevix-Trench, Georgia, Beesley, Jonathan, Chen, Xiaoqing, Investigators, for kConFab, Group, Australian Ovarian Cancer Study, Lambrechts, Diether, Smeets, Ann, Paridaens, Robert, Weltens, Caroline, Flesch-Janys, Dieter, Buck, Katharina, Behrens, Sabine, Peterlongo, Paolo, Bernard, Loris, Manoukian, Siranoush, Radice, Paolo, Couch, Fergus J, Vachon, Celine, Wang, Xianshu, and Olson, Janet
Subjects: Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Aging, Breast Cancer, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Aged, Breast Neoplasms, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 9, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, GENICA Network, kConFab Investigators, Australian Ovarian Cancer Study Group, Medical and Health Sciences, Epidemiology, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundOur recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).MethodsTo further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls).ResultsThis replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10(-29)] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 0.43). rs865686 was associated with estrogen receptor-positive (ER(+)) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10(-22)) but less strongly, if at all, with ER-negative (ER(-)) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; P(het) = 1.16 × 10(-6)), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER(+) tumors.ConclusionsThis study is the first to show that rs865686 is a susceptibility marker for ER(+) breast cancer.ImpactThe findings further support the view that genetic susceptibility varies according to tumor subtype.
Published: 2012

45. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Author: Hein, Rebecca, Maranian, Melanie, Hopper, John L, Kapuscinski, Miroslaw K, Southey, Melissa C, Park, Daniel J, Schmidt, Marjanka K, Broeks, Annegien, Hogervorst, Frans B. L, Bueno-de-Mesquit, H. Bas, Muir, Kenneth R, Lophatananon, Artitaya, Rattanamongkongul, Suthee, Puttawibul, Puttisak, Fasching, Peter A, Hein, Alexander, Ekici, Arif B, Beckmann, Matthias W, Fletcher, Olivia, Johnson, Nichola, dos Santos Silva, Isabel, Peto, Julian, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Miller, Nicola, Marmee, Frederick, Schneeweiss, Andreas, Sohn, Christof, Burwinkel, Barbara, GuÃ©nel, Pascal, Cordina-Duverger, Emilie, Menegaux, Florence, Truong, ThÃ©rÃ¨se, Bojesen, Stig E, Nordestgaard, BÃ¸rge G, Flyger, Henrik, Milne, Roger L, Perez, Jose Ignacio Arias, Zamora, M. Pilar, BenÃtez, Javier, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Clarke, Christina A, Brenner, Hermann, MÃ¼ller, Heiko, Arndt, Volker, Stegmaier, Christa, Rahman, Nazneen, Seal, Sheila, Turnbull, Clare, Renwick, Anthony, Meindl, Alfons, Schott, Sarah, Bartram, Claus R, Schmutzler, Rita K, Brauch, Hiltrud, Hamann, Ute, Ko, Yon-Dschun, Wang-Gohrke, Shan, Dark, Thilo, Scharmann, Peter, Karstens, Johann H, Hillemanns, Peter, Nevanlinna, Heli, Heikkinen, Tuomas, AittomÃ¤ki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia V, Zalutsky, Iosif V, Antonenkova, Natalia N, Bermisheva, Marina, Prokovieva, Darya, Farahtdinova, Albina, Khusnutdinova, Elza, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana, Chen, Xiaoqing, Beesley, Jonathan, Investigators, kConFab, Lambrechts, Diether, Zhao, Hui, Neven, Patrick, Wildiers, Hans, Nickels, Stefan, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Barile, Monica, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, and Giles, Graham G
Subjects: susceptibility locus, chinese, women
Published: 2012

46. Genome-wide association analysis identifies three new breast cancer susceptibility loci

Author: Ghoussaini, Maya, Fletcher, Olivia, Michailidou, Kyriaki, Turnbull, Clare, Schmidt, Marjanka K, Dicks, Ed, Dennis, Joe, Wang, Qin, Humphreys, Manjeet K, Luccarini, Craig, Baynes, Caroline, Conroy, Don, Maranian, Melanie, Ahmed, Shahana, Driver, Kristy, Johnson, Nichola, Orr, Nicholas, dos Santos Silva, Isabel, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Uitterlinden, Andre G, Rivadeneira, Fernando, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Nevanlinna, Heli, Aittomäki, Kristiina, Blomqvist, Carl, Meindl, Alfons, Schmutzler, Rita K, Müller-Myhsok, Bertram, Lichtner, Peter, Chang-Claude, Jenny, Hein, Rebecca, Nickels, Stefan, Flesch-Janys, Dieter, Tsimiklis, Helen, Makalic, Enes, Schmidt, Daniel, Bui, Minh, Hopper, John L, Apicella, Carmel, Park, Daniel J, Southey, Melissa, Hunter, David J, Chanock, Stephen J, Broeks, Annegien, Verhoef, Senno, Hogervorst, Frans BL, Fasching, Peter A, Lux, Michael P, Beckmann, Matthias W, Ekici, Arif B, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Burwinkel, Barbara, Guénel, Pascal, Truong, Thérèse, Cordina-Duverger, Emilie, Menegaux, Florence, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Milne, Roger L, Alonso, M Rosario, González-Neira, Anna, Benítez, Javier, Anton-Culver, Hoda, Ziogas, Argyrios, Bernstein, Leslie, Dur, Christina Clarke, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Stegmaier, Christa, Justenhoven, Christina, Brauch, Hiltrud, Brüning, Thomas, Wang-Gohrke, Shan, Eilber, Ursula, Dörk, Thilo, Schürmann, Peter, Bremer, Michael, Hillemanns, Peter, Bogdanova, Natalia V, Antonenkova, Natalia N, Rogov, Yuri I, Karstens, Johann H, Bermisheva, Marina, Prokofieva, Darya, Khusnutdinova, Elza, Lindblom, Annika, Margolin, Sara, and Mannermaa, Arto
Subjects: Biological Sciences, Genetics, Estrogen, Human Genome, Prevention, Cancer, Breast Cancer, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 21, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Logistic Models, Polymorphism, Single Nucleotide, Principal Component Analysis, White People, Netherlands Collaborative Group on Hereditary Breast and Ovarian Cancer, Familial Breast Cancer Study, Gene Environment Interaction of Breast Cancer in Germany (GENICA) Network, kConFab Investigators, Australian Ovarian Cancer Study Group, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.
Published: 2012

47. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

Author: Kirchhoff, Tomas, Gaudet, Mia M, Antoniou, Antonis C, McGuffog, Lesley, Humphreys, Manjeet K, Dunning, Alison M, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Dork, Thilo, Schürmann, Peter, Karstens, Johann H, Hillemanns, Peter, Couch, Fergus J, Olson, Janet, Vachon, Celine, Wang, Xianshu, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Burwinkel, Barbara, Meindl, Alfons, Brauch, Hiltrud, Hamann, Ute, Ko, Yon-Dschun, GENICA Network, Broeks, Annegien, Schmidt, Marjanka K, Van 't Veer, Laura J, Braaf, Linde M, Johnson, Nichola, Fletcher, Olivia, Gibson, Lorna, Peto, Julian, Turnbull, Clare, Seal, Sheila, Renwick, Anthony, Rahman, Nazneen, Wu, Pei-Ei, Yu, Jyh-Cherng, Hsiung, Chia-Ni, Shen, Chen-Yang, Southey, Melissa C, Hopper, John L, Hammet, Fleur, Van Dorpe, Thijs, Dieudonne, Anne-Sophie, Hatse, Sigrid, Lambrechts, Diether, Andrulis, Irene L, Bogdanova, Natalia, Antonenkova, Natalia, Rogov, Juri I, Prokofieva, Daria, Bermisheva, Marina, Khusnutdinova, Elza, van Asperen, Christi J, Tollenaar, Robert AEM, Hooning, Maartje J, Devilee, Peter, Margolin, Sara, Lindblom, Annika, Milne, Roger L, Arias, José Ignacio, Zamora, M Pilar, Benítez, Javier, Severi, Gianluca, Baglietto, Laura, Giles, Graham G, kConFab, AOCS Study Group, Spurdle, Amanda B, Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, Healey, Sue, Wang-Gohrke, Shan, Chang-Claude, Jenny, Mannermaa, Arto, Kosma, Veli-Matti, Kauppinen, Jaana, Kataja, Vesa, Agnarsson, Bjarni A, Caligo, Maria A, Godwin, Andrew K, Nevanlinna, Heli, Heikkinen, Tuomas, Fredericksen, Zachary, Lindor, Noralane, Nathanson, Katherine L, Domchek, Susan M, SWE-BRCA, Loman, Niklas, Karlsson, Per, and Stenmark Askmalm, Marie
Subjects: GENICA Network, kConFab, AOCS Study Group, SWE-BRCA, HEBON, EMBRACE, BCAC/CIMBA, Chromosomes, Human, Pair 6, Humans, Breast Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Receptors, Estrogen, Confidence Intervals, Proportional Hazards Models, Odds Ratio, Risk Factors, Heterozygote, Polymorphism, Single Nucleotide, Alleles, Middle Aged, Female, Genetic Association Studies, Chromosomes, Human, Pair 6, Polymorphism, Single Nucleotide, Receptors, Estrogen, General Science & Technology
Abstract: Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p =
Published: 2012

48. Risk of Estrogen Receptor–Positive and –Negative Breast Cancer and Single–Nucleotide Polymorphism 2q35-rs13387042

Author: Milne, Roger L, Benítez, Javier, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomäki, Kristiina, Blomqvist, Carl, Arias, José Ignacio, Zamora, M Pilar, Burwinkel, Barbara, Bartram, Claus R, Meindl, Alfons, Schmutzler, Rita K, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Southey, Melissa C, Smith, Letitia, Spurdle, Amanda B, Hopper, John L, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, Schürmann, Peter, Bremer, Michael, Hillemanns, Peter, Dörk, Thilo, Devilee, Peter, van Asperen, Christie J, Tollenaar, Rob AEM, Seynaeve, Caroline, Hall, Per, Czene, Kamila, Liu, Jianjun, Li, Yuqing, Ahmed, Shahana, Dunning, Alison M, Maranian, Melanie, Pharoah, Paul DP, Chenevix-Trench, Georgia, Beesley, Jonathan, Investigators, kConFab, Group, AOCS, Bogdanova, Natalia V, Antonenkova, Natalia N, Zalutsky, Iosif V, Anton-Culver, Hoda, Ziogas, Argyrios, Brauch, Hiltrud, Justenhoven, Christina, Ko, Yon-Dschun, Haas, Susanne, Fasching, Peter A, Strick, Reiner, Ekici, Arif B, Beckmann, Matthias W, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, English, Dallas R, Fletcher, Olivia, Johnson, Nichola, dos Santos Silva, Isabel, Peto, Julian, Turnbull, Clare, Hines, Sarah, Renwick, Anthony, Rahman, Nazneen, Nordestgaard, Børge G, Bojesen, Stig E, Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, García-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Brinton, Louise A, Chang-Claude, Jenny, Wang-Gohrke, Shan, Shen, Chen-Yang, Wang, Hui-Chun, Yu, Jyh-Cherng, Chen, Sou-Tong, Bermisheva, Marina, Nikolaeva, Tatjana, Khusnutdinova, Elza, Humphreys, Manjeet K, Morrison, Jonathan, Platte, Radka, Easton, Douglas F, and Consortium, on behalf of the Breast Cancer Association
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Breast Cancer, Clinical Research, Cancer, Human Genome, Estrogen, Adult, Aged, Asian People, Biomarkers, Tumor, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Intraductal, Noninfiltrating, Case-Control Studies, Confidence Intervals, Confounding Factors, Epidemiologic, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Middle Aged, Neoplasms, Hormone-Dependent, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, White People, kConFab Investigators, AOCS Group, Breast Cancer Association Consortium, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
Published: 2009

49. Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases

Author: Figlioli, Gisella, Billaud, Amandine, Wang, Qin, Bolla, Manjeet K, Dennis, Joe, Lush, Michael, Kvist, Anders, Adank, Muriel A, Ahearn, Thomas U, Antonenkova, Natalia N, Auvinen, Päivi, Behrens, Sabine, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brüning, Thomas, Camp, Nicola J, Campbell, Archie, Castelao, Jose E, Cessna, Melissa H, Nbcs Collaborators, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Eriksson, Mikael, Fasching, Peter A, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Closas, Montserrat, Glendon, Gord, Gómez Garcia, Encarna B, González-Neira, Anna, Grassmann, Felix, Guénel, Pascal, Hahnen, Eric, Hamann, Ute, Hillemanns, Peter, Hooning, Maartje J, Hoppe, Reiner, Howell, Anthony, Humphreys, Keith, KConFab Investigators, Jakubowska, Anna, Khusnutdinova, Elza K, Kristensen, Vessela N, Lindblom, Annika, Loizidou, Maria A, Lubiński, Jan, Mannermaa, Arto, Maurer, Tabea, Mavroudis, Dimitrios, Newman, William G, Obi, Nadia, Panayiotidis, Mihalis I, Radice, Paolo, Rashid, Muhammad U, Rhenius, Valerie, Ruebner, Matthias, Saloustros, Emmanouil, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Shah, Mitul, Southey, Melissa C, Tomlinson, Ian, Truong, Thérèse, Van Veen, Elke M, Wendt, Camilla, Yang, Xiaohong R, Michailidou, Kyriaki, Dunning, Alison M, Pharoah, Paul DP, Easton, Douglas F, Andrulis, Irene L, Evans, D Gareth, Hollestelle, Antoinette, Chang-Claude, Jenny, Milne, Roger L, Peterlongo, Paolo, Figlioli, Gisella [0000-0002-0740-1363], Dennis, Joe [0000-0003-4591-1214], Kvist, Anders [0000-0002-1358-0695], Behrens, Sabine [0000-0002-9714-104X], Bogdanova, Natalia V [0000-0002-9736-4593], Bonanni, Bernardo [0000-0003-3589-2128], Camp, Nicola J [0000-0002-4788-1998], Campbell, Archie [0000-0003-0198-5078], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Eriksson, Mikael [0000-0001-8135-4270], Fasching, Peter A [0000-0003-4885-8471], González-Neira, Anna [0000-0002-5421-2020], Hamann, Ute [0000-0001-6705-7624], Hillemanns, Peter [0000-0001-9829-3531], Humphreys, Keith [0000-0002-7458-8252], Jakubowska, Anna [0000-0002-5650-0501], Loizidou, Maria A [0000-0003-4503-7758], Newman, William G [0000-0002-6382-4678], Obi, Nadia [0000-0002-0903-9142], Panayiotidis, Mihalis I [0000-0002-1450-3552], Radice, Paolo [0000-0001-6298-4111], Rashid, Muhammad U [0000-0002-7684-3122], Saloustros, Emmanouil [0000-0002-0485-0120], Schmidt, Marjanka K [0000-0002-2228-429X], van Veen, Elke M [0000-0001-8618-2332], Michailidou, Kyriaki [0000-0001-7065-1237], Pharoah, Paul DP [0000-0001-8494-732X], Andrulis, Irene L [0000-0002-4226-6435], Evans, D Gareth [0000-0002-8482-5784], Hollestelle, Antoinette [0000-0003-1166-1966], Chang-Claude, Jenny [0000-0001-8919-1971], Peterlongo, Paolo [0000-0001-6951-6855], and Apollo - University of Cambridge Repository
Subjects: breast cancer predisposition, protein truncating variants, FANCM PTVs spectrum, PTVs, breast cancer risk factors
Abstract: FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.
Published: 2023

50. Data from 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

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