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696 results on '"Heikkilä, Päivi"'

1. NTHL1 is a recessive cancer susceptibility gene

Author

Nurmi, Anna K., Pelttari, Liisa M., Kiiski, Johanna I., Khan, Sofia, Nurmikolu, Mika, Suvanto, Maija, Aho, Niina, Tasmuth, Tiina, Kalso, Eija, Schleutker, Johanna, Kallioniemi, Anne, Heikkilä, Päivi, Aittomäki, Kristiina, Blomqvist, Carl, and Nevanlinna, Heli

Published
2023
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12. Deep learning quantification reveals a fundamental prognostic role for ductular reaction in biliary atresia

Author

Nyholm, Iiris, primary, Sjöblom, Nelli, additional, Pihlajoki, Marjut, additional, Hukkinen, Maria, additional, Lohi, Jouko, additional, Heikkilä, Päivi, additional, Mutka, Aino, additional, Jahnukainen, Timo, additional, Davenport, Mark, additional, Heikinheimo, Markku, additional, Arola, Johanna, additional, and Pakarinen, Mikko P., additional

Published
2023
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13. Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer

Author

Munne, Pauliina M., Martikainen, Lahja, Räty, Iiris, Bertula, Kia, Nonappa, Ruuska, Janika, Ala-Hongisto, Hanna, Peura, Aino, Hollmann, Babette, Euro, Lilya, Yavuz, Kerim, Patrikainen, Linda, Salmela, Maria, Pokki, Juho, Kivento, Mikko, Väänänen, Juho, Suomi, Tomi, Nevalaita, Liina, Mutka, Minna, Kovanen, Panu, Leidenius, Marjut, Meretoja, Tuomo, Hukkinen, Katja, Monni, Outi, Pouwels, Jeroen, Sahu, Biswajyoti, Mattson, Johanna, Joensuu, Heikki, Heikkilä, Päivi, Elo, Laura L., Metcalfe, Ciara, Junttila, Melissa R., Ikkala, Olli, and Klefström, Juha

Published
2021
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14. Prediction of renal outcome in Henoch-Schönlein nephritis based on biopsy findings

Author

Koskela, Mikael, Ylinen, Elisa, Autio-Harmainen, Helena, Tokola, Heikki, Heikkilä, Päivi, Lohi, Jouko, Jalanko, Hannu, Nuutinen, Matti, and Jahnukainen, Timo

Subjects
Kidneys -- Biopsy, Nephritis -- Diagnosis -- Prognosis, Schonlein-Henoch purpura -- Diagnosis -- Prognosis, Pediatric research, Health
Abstract

Background In Henoch-Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable. Methods We evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up. Results Between the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p < 0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053). Conclusions Our results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction., Author(s): Mikael Koskela [sup.1] [sup.2] , Elisa Ylinen [sup.2] , Helena Autio-Harmainen [sup.3] , Heikki Tokola [sup.3] , Päivi Heikkilä [sup.4] , Jouko Lohi [sup.4] , Hannu Jalanko [sup.2] , [...]

Published
2020
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15. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.

Author

Spurdle, Amanda B, Couch, Fergus J, Parsons, Michael T, McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K, Wang, Qin, Healey, Sue, Schmutzler, Rita, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L, Domchek, Susan M, Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Åke, Andrulis, Irene L, Miron, Alexander, Hansen, Thomas VO, Caldes, Trinidad, Neuhausen, Susan L, Toland, Amanda E, Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K, Osorio, Ana, Factor, Rachel E, Terry, Mary B, Rebbeck, Timothy R, Karlan, Beth Y, Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul DP, Blows, Fiona M, Dunning, Alison M, Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Slamon, Dennis J, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A, Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J, and Brinton, Louise

Subjects
ABCTB Investigators, EMBRACE Group, GENICA Network, HEBON Group, kConFab Investigators, Humans, Carcinoma, Breast Neoplasms, Receptor, erbB-2, Receptors, Estrogen, Receptors, Progesterone, Neoplasm Staging, Likelihood Functions, Age Factors, Mutation, Genes, BRCA1, Genes, BRCA2, Adult, Aged, Middle Aged, Female, Neoplasm Grading, Triple Negative Breast Neoplasms, Receptor, ErbB-2, Receptor, erbB-2, Receptors, Estrogen, Progesterone, Genes, BRCA1, BRCA2, ErbB-2, Prevention, Breast Cancer, Cancer, Genetics, 4.2 Evaluation of markers and technologies, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

IntroductionThe distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.MethodsSelection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.ResultsER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).ConclusionsThese results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.

Published
2014

16. Refined histopathological predictors of BRCA1 and BRCA2mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Author

Spurdle, Amanda B, Couch, Fergus J, Parsons, Michael T, McGuffog, Lesley, Barrowdale, Daniel, Bolla, Manjeet K, Wang, Qin, Healey, Sue, Schmutzler, Rita Katharina, Wappenschmidt, Barbara, Rhiem, Kerstin, Hahnen, Eric, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, Varon-Mateeva, Raymonda, Ellis, Steve, Frost, Debra, Platte, Radka, Perkins, Jo, Evans, D Gareth, Izatt, Louise, Eeles, Ros, Adlard, Julian, Davidson, Rosemarie, Cole, Trevor, Scuvera, Giulietta, Manoukian, Siranoush, Bonanni, Bernardo, Mariette, Frederique, Fortuzzi, Stefano, Viel, Alessandra, Pasini, Barbara, Papi, Laura, Varesco, Liliana, Balleine, Rosemary, Nathanson, Katherine L, Domchek, Susan M, Offitt, Kenneth, Jakubowska, Anna, Lindor, Noralane, Thomassen, Mads, Jensen, Uffe Birk, Rantala, Johanna, Borg, Åke, Andrulis, Irene L, Miron, Alexander, Hansen, Thomas VO, Caldes, Trinidad, Neuhausen, Susan L, Toland, Amanda E, Nevanlinna, Heli, Montagna, Marco, Garber, Judy, Godwin, Andrew K, Osorio, Ana, Factor, Rachel E, Terry, Mary B, Rebbeck, Timothy R, Karlan, Beth Y, Southey, Melissa, Rashid, Muhammad Usman, Tung, Nadine, Pharoah, Paul DP, Blows, Fiona M, Dunning, Alison M, Provenzano, Elena, Hall, Per, Czene, Kamila, Schmidt, Marjanka K, Broeks, Annegien, Cornelissen, Sten, Verhoef, Senno, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Slamon, Dennis J, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Chang-Claude, Jenny, Flesch-Janys, Dieter, Rudolph, Anja, Seibold, Petra, Aittomäki, Kristiina, Muranen, Taru A, Heikkilä, Päivi, Blomqvist, Carl, Figueroa, Jonine, Chanock, Stephen J, and Brinton, Louise

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Prevention, Genetics, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adult, Age Factors, Aged, Breast Neoplasms, Carcinoma, Female, Genes, BRCA1, Genes, BRCA2, Humans, Likelihood Functions, Middle Aged, Mutation, Neoplasm Grading, Neoplasm Staging, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Triple Negative Breast Neoplasms, ABCTB Investigators, EMBRACE Group, GENICA Network, HEBON Group, kConFab Investigators, Receptor, erbB-2, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.

Published
2014

17. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.

Author

Purrington, Kristen, Slager, Susan, Eccles, Diana, Yannoukakos, Drakoulis, Fasching, Peter, Miron, Penelope, Carpenter, Jane, Chang-Claude, Jenny, Martin, Nicholas, Montgomery, Grant, Kristensen, Vessela, Goodfellow, Paul, Tapper, William, Rafiq, Sajjad, Gerty, Susan, Durcan, Lorraine, Konstantopoulou, Irene, Fostira, Florentia, Vratimos, Athanassios, Apostolou, Paraskevi, Konstanta, Irene, Kotoula, Vassiliki, Lakis, Sotiris, Dimopoulos, Meletios, Skarlos, Dimosthenis, Pectasides, Dimitrios, Fountzilas, George, Beckmann, Matthias, Hein, Alexander, Ruebner, Matthias, Ekici, Arif, Hartmann, Arndt, Schulz-Wendtland, Ruediger, Renner, Stefan, Janni, Wolfgang, Rack, Brigitte, Scholz, Christoph, Neugebauer, Julia, Andergassen, Ulrich, Lux, Michael, Haeberle, Lothar, Clarke, Christine, Pathmanathan, Nirmala, Rudolph, Anja, Flesch-Janys, Dieter, Nickels, Stefan, Olson, Janet, Ingle, James, Olswold, Curtis, Slettedahl, Seth, Eckel-Passow, Jeanette, Anderson, S, Visscher, Daniel, Cafourek, Victoria, Sicotte, Hugues, Prodduturi, Naresh, Weiderpass, Elisabete, Bernstein, Leslie, Ivanovich, Jennifer, Giles, Graham, Baglietto, Laura, Southey, Melissa, Kosma, Veli-Matti, Fischer, Hans-Peter, Reed, Malcom, Cross, Simon, Deming-Halverson, Sandra, Shrubsole, Martha, Cai, Qiuyin, Shu, Xiao-Ou, Daly, Mary, Weaver, Joellen, Ross, Eric, Klemp, Jennifer, Sharma, Priyanka, Torres, Diana, Rüdiger, Thomas, Wölfing, Heidrun, Ulmer, Hans-Ulrich, Försti, Asta, Khoury, Thaer, Kumar, Shicha, Pilarski, Robert, Shapiro, Charles, Greco, Dario, Heikkilä, Päivi, Aittomäki, Kristiina, Blomqvist, Carl, Irwanto, Astrid, Liu, Jianjun, Pankratz, Vernon, Wang, Xianshu, Severi, Gianluca, Mannermaa, Arto, Easton, Douglas, Hall, Per, Brauch, Hiltrud, Cox, Angela, Zheng, Wei, and Godwin, Andrew

Subjects
Adult, Aged, Aged, 80 and over, Case-Control Studies, Chromosomes, Human, Pair 19, Estrogen Receptor alpha, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Triple Negative Breast Neoplasms, Young Adult
Abstract

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

Published
2014

18. Functional Variants at the 11q13 Risk Locus for Breast Cancer Regulate Cyclin D1 Expression through Long-Range Enhancers

Author

French, Juliet D, Ghoussaini, Maya, Edwards, Stacey L, Meyer, Kerstin B, Michailidou, Kyriaki, Ahmed, Shahana, Khan, Sofia, Maranian, Mel J, O’Reilly, Martin, Hillman, Kristine M, Betts, Joshua A, Carroll, Thomas, Bailey, Peter J, Dicks, Ed, Beesley, Jonathan, Tyrer, Jonathan, Maia, Ana-Teresa, Beck, Andrew, Knoblauch, Nicholas W, Chen, Constance, Kraft, Peter, Barnes, Daniel, González-Neira, Anna, Alonso, M Rosario, Herrero, Daniel, Tessier, Daniel C, Vincent, Daniel, Bacot, Francois, Luccarini, Craig, Baynes, Caroline, Conroy, Don, Dennis, Joe, Bolla, Manjeet K, Wang, Qin, Hopper, John L, Southey, Melissa C, Schmidt, Marjanka K, Broeks, Annegien, Verhoef, Senno, Cornelissen, Sten, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, Pornthep, Fasching, Peter A, Loehberg, Christian R, Ekici, Arif B, Beckmann, Matthias W, Peto, Julian, dos Santos Silva, Isabel, Johnson, Nichola, Aitken, Zoe, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Burwinkel, Barbara, Guénel, Pascal, Truong, Thérèse, Laurent-Puig, Pierre, Menegaux, Florence, Bojesen, Stig E, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Milne, Roger L, Zamora, M Pilar, Perez, Jose Ignacio Arias, Benitez, Javier, Anton-Culver, Hoda, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Stegmaier, Christa, Meindl, Alfons, Lichtner, Peter, Schmutzler, Rita K, Engel, Christoph, Brauch, Hiltrud, Hamann, Ute, Justenhoven, Christina, Network, The GENICA, Aaltonen, Kirsimari, Heikkilä, Päivi, Aittomäki, Kristiina, Blomqvist, Carl, Matsuo, Keitaro, Ito, Hidemi, Iwata, Hiroji, Sueta, Aiko, Bogdanova, Natalia V, Antonenkova, Natalia N, Dörk, Thilo, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, and Kataja, Vesa

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Breast Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Binding Sites, Breast Neoplasms, Case-Control Studies, Cell Line, Tumor, Chromatin, Chromatin Immunoprecipitation, Chromosomes, Human, Pair 11, Cyclin D1, Electrophoretic Mobility Shift Assay, Enhancer Elements, Genetic, Female, GATA3 Transcription Factor, Gene Expression Regulation, Neoplastic, Humans, Luciferases, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, RNA, Messenger, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Silencer Elements, Transcriptional, ets-Domain Protein Elk-4, GENICA Network, kConFab Investigators, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.

Published
2013

20. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

Author

Yang, Xiaohong R, Chang-Claude, Jenny, Goode, Ellen L, Couch, Fergus J, Nevanlinna, Heli, Milne, Roger L, Gaudet, Mia, Schmidt, Marjanka K, Broeks, Annegien, Cox, Angela, Fasching, Peter A, Hein, Rebecca, Spurdle, Amanda B, Blows, Fiona, Driver, Kristy, Flesch-Janys, Dieter, Heinz, Judith, Sinn, Peter, Vrieling, Alina, Heikkinen, Tuomas, Aittomäki, Kristiina, Heikkilä, Päivi, Blomqvist, Carl, Lissowska, Jolanta, Peplonska, Beata, Chanock, Stephen, Figueroa, Jonine, Brinton, Louise, Hall, Per, Czene, Kamila, Humphreys, Keith, Darabi, Hatef, Liu, Jianjun, Van 't Veer, Laura J, van Leeuwen, Flora E, Andrulis, Irene L, Glendon, Gord, Knight, Julia A, Mulligan, Anna Marie, O'Malley, Frances P, Weerasooriya, Nayana, John, Esther M, Beckmann, Matthias W, Hartmann, Arndt, Weihbrecht, Sebastian B, Wachter, David L, Jud, Sebastian M, Loehberg, Christian R, Baglietto, Laura, English, Dallas R, Giles, Graham G, McLean, Catriona A, Severi, Gianluca, Lambrechts, Diether, Vandorpe, Thijs, Weltens, Caroline, Paridaens, Robert, Smeets, Ann, Neven, Patrick, Wildiers, Hans, Wang, Xianshu, Olson, Janet E, Cafourek, Victoria, Fredericksen, Zachary, Kosel, Matthew, Vachon, Celine, Cramp, Helen E, Connley, Daniel, Cross, Simon S, Balasubramanian, Sabapathy P, Reed, Malcolm WR, Dörk, Thilo, Bremer, Michael, Meyer, Andreas, Karstens, Johann H, Ay, Aysun, Park-Simon, Tjoung-Won, Hillemanns, Peter, Arias Pérez, Jose Ignacio, Menéndez Rodríguez, Primitiva, Zamora, Pilar, Benítez, Javier, Ko, Yon-Dschun, Fischer, Hans-Peter, Hamann, Ute, Pesch, Beate, Brüning, Thomas, Justenhoven, Christina, Brauch, Hiltrud, Eccles, Diana M, Tapper, William J, Gerty, Sue M, Sawyer, Elinor J, Tomlinson, Ian P, Jones, Angela, Kerin, Michael, Miller, Nicola, McInerney, Niall, Anton-Culver, Hoda, and Ziogas, Argyrios

Subjects
Humans, Breast Neoplasms, Obesity, Receptor, erbB-2, Receptors, Estrogen, Receptors, Progesterone, Body Mass Index, Logistic Models, Odds Ratio, Risk Factors, Case-Control Studies, Age Factors, Parity, Parturition, Menarche, Female, Keratin-5, ErbB Receptors, Biomarkers, Tumor, Receptor, ErbB-2, Prevention, Cancer, Aging, Breast Cancer, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPrevious studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.MethodsWe pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.ResultsIn case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.ConclusionsThis study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Published
2011

26. Somatic Deletions in Hereditary Breast Cancers Implicate 13q21 as a Putative Novel Breast Cancer Susceptibility Locus

Author

Kainu, Tommi, Juo, Suh-Hang Hank, Desper, Richard, Schaffer, Alejandro A., Gillanders, Elizabeth, Rozenblum, Ester, Freas-Lutz, Diana, Weaver, Don, Stephan, Dietrich, Bailey-Wilson, Joan, Trikkonen, Mika, Syrjakoski, Kirsi, Kuukasjarvi, Tuula, Koivisto, Pasi, Karhu, Ritva, Holli, Kaija, Arason, Adalgeir, Johannesdottir, Gudrun, Bergthorsson, Jon Thor, Johannsdottir, Hrefna, Egilsson, Valgardur, Barkardottir, Rosa Bjork, Johannsson, Oskar, Haraldsson, Karin, Sandberg, Therese, Holmberg, Eva, Gronberg, Henrik, Olsson, Hakan, Borg, Ake, Vehmanen, Paula, Eerola, Hannaleena, Heikkila, Paivi, Pyrhonen, Seppo, and Nevanlinna, Heli

Published
2000

29. Supplementary Data from Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening

Author

Sihto, Harri, primary, Lundin, Johan, primary, Lehtimäki, Tiina, primary, Sarlomo-Rikala, Maarit, primary, Bützow, Ralf, primary, Holli, Kaija, primary, Sailas, Liisa, primary, Kataja, Vesa, primary, Lundin, Mikael, primary, Turpeenniemi-Hujanen, Taina, primary, Isola, Jorma, primary, Heikkilä, Päivi, primary, and Joensuu, Heikki, primary

Published
2023
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31. Supplementary Tables 1-9 from Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Author

Mavaddat, Nasim, primary, Barrowdale, Daniel, primary, Andrulis, Irene L., primary, Domchek, Susan M., primary, Eccles, Diana, primary, Nevanlinna, Heli, primary, Ramus, Susan J., primary, Spurdle, Amanda, primary, Robson, Mark, primary, Sherman, Mark, primary, Mulligan, Anna Marie, primary, Couch, Fergus J., primary, Engel, Christoph, primary, McGuffog, Lesley, primary, Healey, Sue, primary, Sinilnikova, Olga M., primary, Southey, Melissa C., primary, Terry, Mary Beth, primary, Goldgar, David, primary, O'Malley, Frances, primary, John, Esther M., primary, Janavicius, Ramunas, primary, Tihomirova, Laima, primary, Hansen, Thomas V. O., primary, Nielsen, Finn C., primary, Osorio, Ana, primary, Stavropoulou, Alexandra, primary, Benítez, Javier, primary, Manoukian, Siranoush, primary, Peissel, Bernard, primary, Barile, Monica, primary, Volorio, Sara, primary, Pasini, Barbara, primary, Dolcetti, Riccardo, primary, Putignano, Anna Laura, primary, Ottini, Laura, primary, Radice, Paolo, primary, Hamann, Ute, primary, Rashid, Muhammad U., primary, Hogervorst, Frans B., primary, Kriege, Mieke, primary, van der Luijt, Rob B., primary, Peock, Susan, primary, Frost, Debra, primary, Evans, D. Gareth, primary, Brewer, Carole, primary, Walker, Lisa, primary, Rogers, Mark T., primary, Side, Lucy E., primary, Houghton, Catherine, primary, Weaver, JoEllen, primary, Godwin, Andrew K., primary, Schmutzler, Rita K., primary, Wappenschmidt, Barbara, primary, Meindl, Alfons, primary, Kast, Karin, primary, Arnold, Norbert, primary, Niederacher, Dieter, primary, Sutter, Christian, primary, Deissler, Helmut, primary, Gadzicki, Doroteha, primary, Preisler-Adams, Sabine, primary, Varon-Mateeva, Raymonda, primary, Schönbuchner, Ines, primary, Gevensleben, Heidrun, primary, Stoppa-Lyonnet, Dominique, primary, Belotti, Muriel, primary, Barjhoux, Laure, primary, Isaacs, Claudine, primary, Peshkin, Beth N., primary, Caldes, Trinidad, primary, de la Hoya, Miguel, primary, Cañadas, Carmen, primary, Heikkinen, Tuomas, primary, Heikkilä, Päivi, primary, Aittomäki, Kristiina, primary, Blanco, Ignacio, primary, Lazaro, Conxi, primary, Brunet, Joan, primary, Agnarsson, Bjarni A., primary, Arason, Adalgeir, primary, Barkardottir, Rosa B., primary, Dumont, Martine, primary, Simard, Jacques, primary, Montagna, Marco, primary, Agata, Simona, primary, D'Andrea, Emma, primary, Yan, Max, primary, Fox, Stephen, primary, Rebbeck, Timothy R., primary, Rubinstein, Wendy, primary, Tung, Nadine, primary, Garber, Judy E., primary, Wang, Xianshu, primary, Fredericksen, Zachary, primary, Pankratz, Vernon S., primary, Lindor, Noralane M., primary, Szabo, Csilla, primary, Offit, Kenneth, primary, Sakr, Rita, primary, Gaudet, Mia M., primary, Singer, Christian F., primary, Tea, Muy-Kheng, primary, Rappaport, Christine, primary, Mai, Phuong L., primary, Greene, Mark H., primary, Sokolenko, Anna, primary, Imyanitov, Evgeny, primary, Toland, Amanda Ewart, primary, Senter, Leigha, primary, Sweet, Kevin, primary, Thomassen, Mads, primary, Gerdes, Anne-Marie, primary, Kruse, Torben, primary, Caligo, Maria, primary, Aretini, Paolo, primary, Rantala, Johanna, primary, von Wachenfeld, Anna, primary, Henriksson, Karin, primary, Steele, Linda, primary, Neuhausen, Susan L., primary, Nussbaum, Robert, primary, Beattie, Mary, primary, Odunsi, Kunle, primary, Sucheston, Lara, primary, Gayther, Simon A., primary, Nathanson, Kate, primary, Gross, Jenny, primary, Walsh, Christine, primary, Karlan, Beth, primary, Chenevix-Trench, Georgia, primary, Easton, Douglas F., primary, and Antoniou, Antonis C., primary

Published
2023
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32. Supplementary Table 1 from The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer

Author

Jönsson, Göran, primary, Staaf, Johan, primary, Vallon-Christersson, Johan, primary, Ringnér, Markus, primary, Gruvberger-Saal, Sofia K., primary, Saal, Lao H., primary, Holm, Karolina, primary, Hegardt, Cecilia, primary, Arason, Adalgeir, primary, Fagerholm, Rainer, primary, Persson, Camilla, primary, Grabau, Dorthe, primary, Johnsson, Ellinor, primary, Lövgren, Kristina, primary, Magnusson, Linda, primary, Heikkilä, Päivi, primary, Agnarsson, Bjarni A., primary, Johannsson, Oskar T., primary, Malmström, Per, primary, Fernö, Mårten, primary, Olsson, Håkan, primary, Loman, Niklas, primary, Nevanlinna, Heli, primary, Barkardottir, Rosa B., primary, and Borg, Åke, primary

Published
2023
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33. Data from The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer

Author

Jönsson, Göran, primary, Staaf, Johan, primary, Vallon-Christersson, Johan, primary, Ringnér, Markus, primary, Gruvberger-Saal, Sofia K., primary, Saal, Lao H., primary, Holm, Karolina, primary, Hegardt, Cecilia, primary, Arason, Adalgeir, primary, Fagerholm, Rainer, primary, Persson, Camilla, primary, Grabau, Dorthe, primary, Johnsson, Ellinor, primary, Lövgren, Kristina, primary, Magnusson, Linda, primary, Heikkilä, Päivi, primary, Agnarsson, Bjarni A., primary, Johannsson, Oskar T., primary, Malmström, Per, primary, Fernö, Mårten, primary, Olsson, Håkan, primary, Loman, Niklas, primary, Nevanlinna, Heli, primary, Barkardottir, Rosa B., primary, and Borg, Åke, primary

Published
2023
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34. ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations

Author

Cserni, Bálint, Kilmartin, Darren, O’Loughlin, Mark, Andreu, Xavier, Bagó-Horváth, Zsuzsanna, Bianchi, Simonetta, Chmielik, Ewa, Figueiredo, Paulo, Floris, Giuseppe, Foschini, Maria Pia, Kovács, Anikó, Heikkilä, Päivi, Kulka, Janina, Laenkholm, Anne Vibeke, Liepniece-Karele, Inta, Marchiò, Caterina, Provenzano, Elena, Regitnig, Peter, Reiner, Angelika, Ryška, Aleš, Sapino, Anna, Stovgaard, Elisabeth Specht, Quinn, Cecily, Zolota, Vasiliki, Webber, Mark, Glynn, Sharon A., Bori, Rita, Csörgő, Erika, Oláh-Németh, Orsolya, Pancsa, Tamás, Sejben, Anita, Sejben, István, Vörös, András, Zombori, Tamás, Nyári, Tibor, Callagy, Grace, Cserni, Gábor, Cserni, Bálint, Kilmartin, Darren, O’Loughlin, Mark, Andreu, Xavier, Bagó-Horváth, Zsuzsanna, Bianchi, Simonetta, Chmielik, Ewa, Figueiredo, Paulo, Floris, Giuseppe, Foschini, Maria Pia, Kovács, Anikó, Heikkilä, Päivi, Kulka, Janina, Laenkholm, Anne Vibeke, Liepniece-Karele, Inta, Marchiò, Caterina, Provenzano, Elena, Regitnig, Peter, Reiner, Angelika, Ryška, Aleš, Sapino, Anna, Stovgaard, Elisabeth Specht, Quinn, Cecily, Zolota, Vasiliki, Webber, Mark, Glynn, Sharon A., Bori, Rita, Csörgő, Erika, Oláh-Németh, Orsolya, Pancsa, Tamás, Sejben, Anita, Sejben, István, Vörös, András, Zombori, Tamás, Nyári, Tibor, Callagy, Grace, and Cserni, Gábor

Abstract

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2–11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.

Published
2023

36. Publisher Correction: Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy

Author

Haikala, Heidi M., Anttila, Johanna M., Marques, Elsa, Raatikainen, Tiina, Ilander, Mette, Hakanen, Henna, Ala-Hongisto, Hanna, Savelius, Mariel, Balboa, Diego, Von Eyss, Bjoern, Eskelinen, Vilja, Munne, Pauliina, Nieminen, Anni I., Otonkoski, Timo, Schüler, Julia, Laajala, Teemu D., Aittokallio, Tero, Sihto, Harri, Mattson, Johanna, Heikkilä, Päivi, Leidenius, Marjut, Joensuu, Heikki, Mustjoki, Satu, Kovanen, Panu, Eilers, Martin, Leverson, Joel D., and Klefström, Juha

Published
2019
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37. Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy

Author

Haikala, Heidi M., Anttila, Johanna M., Marques, Elsa, Raatikainen, Tiina, Ilander, Mette, Hakanen, Henna, Ala-Hongisto, Hanna, Savelius, Mariel, Balboa, Diego, Von Eyss, Bjoern, Eskelinen, Vilja, Munne, Pauliina, Nieminen, Anni I., Otonkoski, Timo, Schüler, Julia, Laajala, Teemu D., Aittokallio, Tero, Sihto, Harri, Mattson, Johanna, Heikkilä, Päivi, Leidenius, Marjut, Joensuu, Heikki, Mustjoki, Satu, Kovanen, Panu, Eilers, Martin, Leverson, Joel D., and Klefström, Juha

Published
2019
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38. ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations

Author

Cserni, Bálint, primary, Kilmartin, Darren, additional, O’Loughlin, Mark, additional, Andreu, Xavier, additional, Bagó-Horváth, Zsuzsanna, additional, Bianchi, Simonetta, additional, Chmielik, Ewa, additional, Figueiredo, Paulo, additional, Floris, Giuseppe, additional, Foschini, Maria Pia, additional, Kovács, Anikó, additional, Heikkilä, Päivi, additional, Kulka, Janina, additional, Laenkholm, Anne-Vibeke, additional, Liepniece-Karele, Inta, additional, Marchiò, Caterina, additional, Provenzano, Elena, additional, Regitnig, Peter, additional, Reiner, Angelika, additional, Ryška, Aleš, additional, Sapino, Anna, additional, Stovgaard, Elisabeth Specht, additional, Quinn, Cecily, additional, Zolota, Vasiliki, additional, Webber, Mark, additional, Glynn, Sharon A., additional, Bori, Rita, additional, Csörgő, Erika, additional, Oláh-Németh, Orsolya, additional, Pancsa, Tamás, additional, Sejben, Anita, additional, Sejben, István, additional, Vörös, András, additional, Zombori, Tamás, additional, Nyári, Tibor, additional, Callagy, Grace, additional, and Cserni, Gábor, additional

Published
2023
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39. Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia

Author

Nyholm, Iiris, primary, Hukkinen, Maria, additional, Pihlajoki, Marjut, additional, Davidson, Joseph R., additional, Tyraskis, Athanasios, additional, Lohi, Jouko, additional, Heikkilä, Päivi, additional, Hänninen, Satu, additional, Andersson, Noora, additional, Eloranta, Katja, additional, Carpén, Olli, additional, Heikinheimo, Markku, additional, Davenport, Mark, additional, and Pakarinen, Mikko P., additional

Published
2023
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41. The impact of coding germline variants on contralateral breast cancer risk and survival

Author

Morra, Anna, Mavaddat, Nasim, Muranen, Taru A, Ahearn, Thomas U, Allen, Jamie, Andrulis, Irene L, Auvinen, Päivi, Becher, Heiko, Behrens, Sabine, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Camp, Nicola J, Carvalho, Sara, Castelao, Jose E, Cessna, Melissa H, Chang-Claude, Jenny, Chenevix-Trench, Georgia, NBCS Collaborators, Czene, Kamila, Decker, Brennan, Dennis, Joe, Dörk, Thilo, Dorling, Leila, Dunning, Alison M, Ekici, Arif B, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine D, Flyger, Henrik, Gago-Dominguez, Manuela, García-Closas, Montserrat, Geurts-Giele, Willemina RR, Giles, Graham G, Guénel, Pascal, Gündert, Melanie, Hahnen, Eric, Hall, Per, Hamann, Ute, Harrington, Patricia A, He, Wei, Heikkilä, Päivi, Hooning, Maartje J, Hoppe, Reiner, Howell, Anthony, Humphreys, Keith, KConFab Investigators, Jakubowska, Anna, Jung, Audrey Y, Keeman, Renske, Kristensen, Vessela N, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Mavroudis, Dimitrios, Milne, Roger L, Mulligan, Anna Marie, Newman, William G, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Pharoah, Paul DP, Rhenius, Valerie, Saloustros, Emmanouil, Sawyer, Elinor J, Schmutzler, Rita K, Shah, Mitul, Spurdle, Amanda B, Tomlinson, Ian, Truong, Thérèse, Van Veen, Elke M, Vreeswijk, Maaike PG, Wang, Qin, Wendt, Camilla, Yang, Xiaohong R, Nevanlinna, Heli, Devilee, Peter, Easton, Douglas F, Schmidt, Marjanka K, Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Dörk, Thilo [0000-0002-9458-0282]

Subjects
Germ Cells, breast cancer susceptibility genes, Genes, BRCA2, Humans, Female, Breast Neoplasms, Genetic Predisposition to Disease, contralateral breast cancer risk, survival, Germ-Line Mutation, coding germline variants
Abstract

Evidence linking coding germline variants in breast cancer (BC)-susceptibility genes other than BRCA1, BRCA2, and CHEK2 with contralateral breast cancer (CBC) risk and breast cancer-specific survival (BCSS) is scarce. The aim of this study was to assess the association of protein-truncating variants (PTVs) and rare missense variants (MSVs) in nine known (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53) and 25 suspected BC-susceptibility genes with CBC risk and BCSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox regression models. Analyses included 34,401 women of European ancestry diagnosed with BC, including 676 CBCs and 3,449 BC deaths; the median follow-up was 10.9 years. Subtype analyses were based on estrogen receptor (ER) status of the first BC. Combined PTVs and pathogenic/likely pathogenic MSVs in BRCA1, BRCA2, and TP53 and PTVs in CHEK2 and PALB2 were associated with increased CBC risk [HRs (95% CIs): 2.88 (1.70-4.87), 2.31 (1.39-3.85), 8.29 (2.53-27.21), 2.25 (1.55-3.27), and 2.67 (1.33-5.35), respectively]. The strongest evidence of association with BCSS was for PTVs and pathogenic/likely pathogenic MSVs in BRCA2 (ER-positive BC) and TP53 and PTVs in CHEK2 [HRs (95% CIs): 1.53 (1.13-2.07), 2.08 (0.95-4.57), and 1.39 (1.13-1.72), respectively, after adjusting for tumor characteristics and treatment]. HRs were essentially unchanged when censoring for CBC, suggesting that these associations are not completely explained by increased CBC risk, tumor characteristics, or treatment. There was limited evidence of associations of PTVs and/or rare MSVs with CBC risk or BCSS for the 25 suspected BC genes. The CBC findings are relevant to treatment decisions, follow-up, and screening after BC diagnosis.

Published
2023
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43. Co-creating a digital service for small business owners’ finance management

Author

Heikkilä Päivi and Maria Johanna Antikainen

Subjects
co-creation, service development, novel digital services, financial services., Management. Industrial management, HD28-70, Technological innovations. Automation, HD45-45.2
Abstract

This paper presents a small-scale qualitative study exploring the everyday finance management of small business owners. The study was conducted by carrying out contextual interviews, combining the approach of business and social sciences. Insights from five study cases were utilised in co-creating a novel digital service targeted to facilitate finance management in the areas identified as challenging or lacking suitable services. The benefits and challenges of the co-creation process are also discussed. The findings increase the current understanding and bring practical implications to the understudied area of co-creation of financial services. For example, the needs for integration of services and graphical presentation of financial data are not met with current service offering and should be supported better. Gamification and social aspects, as well as, the need for mobile use, are seen as interesting elements for future research.

Published
2015
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47. Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes

Author

Purrington, Kristen S., Visscher, Daniel W., Wang, Chen, Yannoukakos, Drakoulis, Hamann, Ute, Nevanlinna, Heli, Cox, Angela, Giles, Graham G., Eckel-Passow, Jeanette E., Lakis, Sotiris, Kotoula, Vassiliki, Fountzilas, George, Kabisch, Maria, Rüdiger, Thomas, Heikkilä, Päivi, Blomqvist, Carl, Cross, Simon S., Southey, Melissa C., Olson, Janet E., Gilbert, Judy, Deming-Halverson, Sandra, Kosma, Veli-Matti, Clarke, Christine, Scott, Rodney, Jones, J. Louise, Zheng, Wei, Mannermaa, Arto, Eccles, Diana M., Vachon, Celine M., Couch, Fergus J., and Jane Carpenter for ABCTC Investigators

Published
2016
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48. Smooth and Resilient Human–Machine Teamwork as an Industry 5.0 Design Challenge

Author

Kaasinen, Eija, Anttila, Anu-Hanna, Heikkilä, Päivi, Laarni, Jari, Koskinen, Hanna, and Väätänen, Antti

Subjects
SDG 7 - Affordable and Clean Energy
Abstract

Smart machine companions such as artificial intelligence (AI) assistants and collaborative robots are rapidly populating the factory floor. Future factory floor workers will work in teams that include both human co-workers and smart machine actors. The visions of Industry 5.0 describe sustainable, resilient, and human-centered future factories that will require smart and resilient capabilities both from next-generation manufacturing systems and human operators. What kinds of approaches can help design these kinds of resilient human–machine teams and collaborations within them? In this paper, we analyze this design challenge, and we propose basing the design on the joint cognitive systems approach. The established joint cognitive systems approach can be complemented with approaches that support human centricity in the early phases of design, as well as in the development of continuously co-evolving human–machine teams. We propose approaches to observing and analyzing the collaboration in human–machine teams, developing the concept of operations with relevant stakeholders, and including ethical aspects in the design and development. We base our work on the joint cognitive systems approach and propose complementary approaches and methods, namely: actor–network theory, the concept of operations and ethically aware design. We identify their possibilities and challenges in designing and developing smooth human–machine teams for Industry 5.0 manufacturing systems

Published
2022

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