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1. Quality of life of women with a screen-detected versus clinically detected breast cancer in the Netherlands: a prospective cohort study

Author

Irzaldy, Abyan, Otten, Johannes D. M., Kregting, Lindy M., van der Molen, Dieuwke R. Mink, Verkooijen, Helena M., van Ravesteyn, Nicolien T., Heijnsdijk, Eveline A. M., Doeksen, Annemiek, van der Pol, Carmen C., Evers, Daniel J., Ernst, Miranda F., Korfage, Ida J., de Koning, Harry J., and Broeders, Mireille J. M.

Published
2024
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7. The activities of suaveolol and other compounds from Hyptis suaveolens and Momordica charantia against the aetiological agents of African trypanosomiasis, leishmaniasis and malaria

Author

Oaikhena, Enimie E., Yahaya, Umar A., Abdulsalami, Sani M., Egbe, Nkechi L., Adeyemi, Modupe M., Ungogo, Marzuq A., Ebiloma, Godwin U., Zoiku, Felix K., Fordjour, Prince A., Elati, Hamza A.A., Quashie, Neils B., Igoli, John O., Gray, Alexander I., Lawson, Christopher, Ferro, Valerie A., and de Koning, Harry P.

Published
2024
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10. Correction: LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Author

Graupera, Isabel, Thiele, Maja, Ma, Ann T., Serra-Burriel, Miquel, Pich, Judit, Fabrellas, Núria, Caballeria, Llorenç, de Knegt, Robert J., Grgurevic, Ivica, Reichert, Mathias, Roulot, Dominique, Schattenberg, Jörn M., Pericas, Juan M., Angeli, Paolo, Tsochatzis, Emmanuel A., Guha, Indra Neil, Garcia-Retortillo, Montserrat, Morillas, Rosa M., Hernández, Rosario, Hoyo, Jordi, Fuentes, Matilde, Madir, Anita, Juanola, Adrià, Soria, Anna, Juan, Marta, Carol, Marta, Diaz, Alba, Detlefsen, Sönke, Toran, Pere, Pera, Guillem, Fournier, Céline, Llorca, Anne, Newsome, Phillip N., Manns, Michael, de Koning, Harry J., Serra-Burriel, Feliu, Cucchietti, Fernando, Arslanow, Anita, Korenjak, Marko, van Kleef, Laurens, Falcó, Josep Lluis, Kamath, Patrick S., Karlsen, Tom H., Castera, Laurent, Lammert, Frank, Krag, Aleksander, and Ginès, Pere

Published
2023
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13. Comprehensive characterization of purine and pyrimidine transport activities in Trichomonas vaginalis and functional cloning of a trichomonad nucleoside transporter

Author

Natto, Manal J, Miyamoto, Yukiko, Munday, Jane C, AlSiari, Tahani A, Al‐Salabi, Mohammed I, Quashie, Neils B, Eze, Anthonius A, Eckmann, Lars, and De Koning, Harry P

Subjects
Biochemistry and Cell Biology, Biological Sciences, Emerging Infectious Diseases, Sexually Transmitted Infections, Biotechnology, Infectious Diseases, Genetics, Infection, Good Health and Well Being, Biological Transport, Cloning, Molecular, Humans, Kinetics, Nucleoside Transport Proteins, Protozoan Proteins, Purines, Pyrimidines, Trichomonas Infections, Trichomonas vaginalis, adenosine transporter, anaerobic parasite, protozoan parasite, purine salvage, trichomonad, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology, Biological sciences
Abstract

Trichomoniasis is a common and widespread sexually-transmitted infection, caused by the protozoan parasite Trichomonas vaginalis. T. vaginalis lacks the biosynthetic pathways for purines and pyrimidines, making nucleoside metabolism a drug target. Here we report the first comprehensive investigation into purine and pyrimidine uptake by T. vaginalis. Multiple carriers were identified and characterized with regard to substrate selectivity and affinity. For nucleobases, a high-affinity adenine transporter, a possible guanine transporter and a low affinity uracil transporter were found. Nucleoside transporters included two high affinity adenosine/guanosine/uridine/cytidine transporters distinguished by different affinities to inosine, a lower affinity adenosine transporter, and a thymidine transporter. Nine Equilibrative Nucleoside Transporter (ENT) genes were identified in the T. vaginalis genome. All were expressed equally in metronidazole-resistant and -sensitive strains. Only TvagENT2 was significantly upregulated in the presence of extracellular purines; expression was not affected by co-culture with human cervical epithelial cells. All TvagENTs were cloned and separately expressed in Trypanosoma brucei. We identified the main broad specificity nucleoside carrier, with high affinity for uridine and cytidine as well as purine nucleosides including inosine, as TvagENT3. The in-depth characterization of purine and pyrimidine transporters provides a critical foundation for the development of new anti-trichomonal nucleoside analogues.

Published
2021

15. Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer

Author

Lam, Stephen, Bai, Chunxue, Baldwin, David R., Chen, Yan, Connolly, Casey, de Koning, Harry, Heuvelmans, Marjolein A., Hu, Ping, Kazerooni, Ella A., Lancaster, Harriet L., Langs, Georg, McWilliams, Annette, Osarogiagbon, Raymond U., Oudkerk, Matthijs, Peters, Matthew, Robbins, Hilary A., Sahar, Liora, Smith, Robert A., Triphuridet, Natthaya, and Field, John

Published
2024
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16. Trade-Offs Between Harms and Benefits of Different Breast Cancer Screening Intervals Among Low-Risk Women

Author

van Ravesteyn, Nicolien T, Schechter, Clyde B, Hampton, John M, Alagoz, Oguzhan, van den Broek, Jeroen J, Kerlikowske, Karla, Mandelblatt, Jeanne S, Miglioretti, Diana L, Sprague, Brian L, Stout, Natasha K, de Koning, Harry J, Trentham-Dietz, Amy, Tosteson, Anna NA, and Network, from the Breast Cancer Surveillance Consortium and the Cancer Intervention and Surveillance Modeling

Subjects
Cancer, Breast Cancer, Health Services, Clinical Research, Prevention, Good Health and Well Being, Aged, Breast Neoplasms, Early Detection of Cancer, False Positive Reactions, Female, Humans, Mammography, Mass Screening, Middle Aged, Risk, Breast Cancer Surveillance Consortium and the Cancer Intervention and Surveillance Modeling Network, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundA paucity of research addresses breast cancer screening strategies for women at lower-than-average breast cancer risk. The aim of this study was to examine screening harms and benefits among women aged 50-74 years at lower-than-average breast cancer risk by breast density.MethodsThree well-established, validated Cancer Intervention and Surveillance Network models were used to estimate the lifetime benefits and harms of different screening scenarios, varying by screening interval (biennial, triennial). Breast cancer deaths averted, life-years and quality-adjusted life-years gained, false-positives, benign biopsies, and overdiagnosis were assessed by relative risk (RR) level (0.6, 0.7, 0.85, 1 [average risk]) and breast density category, for US women born in 1970.ResultsScreening benefits decreased proportionally with decreasing risk and with lower breast density. False-positives, unnecessary biopsies, and the percentage overdiagnosis also varied substantially by breast density category; false-positives and unnecessary biopsies were highest in the heterogeneously dense category. For women with fatty or scattered fibroglandular breast density and a relative risk of no more than 0.85, the additional deaths averted and life-years gained were small with biennial vs triennial screening. For these groups, undergoing 4 additional screens (screening biennially [13 screens] vs triennially [9 screens]) averted no more than 1 additional breast cancer death and gained no more than 16 life-years and no more than 10 quality-adjusted life-years per 1000 women but resulted in up to 232 more false-positives per 1000 women.ConclusionTriennial screening from age 50 to 74 years may be a reasonable screening strategy for women with lower-than-average breast cancer risk and fatty or scattered fibroglandular breast density.

Published
2021

17. Deazapurine Nucleoside Analogues for the Treatment of Trichomonas vaginalis

Author

Natto, Manal J, Hulpia, Fabian, Kalkman, Eric R, Baillie, Susan, Alhejeli, Amani, Miyamoto, Yukiko, Eckmann, Lars, Van Calenbergh, Serge, and de Koning, Harry P

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Sexually Transmitted Infections, Biotechnology, Infectious Diseases, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Animals, Drug Resistance, High-Throughput Screening Assays, Humans, Mice, Nucleosides, Sexually Transmitted Diseases, Trichomonas vaginalis, nucleoside analog, high-throughput screening, tubercidin, mouse model, Medical microbiology
Abstract

Trichomoniasis is the most common nonviral sexually transmitted disease in humans, but treatment options are limited. Here, we report a resorufin-based drug sensitivity assay for high-throughput microplate-based screening under hypoxic conditions. A 5203-compound enamine kinase library and several specialized compound series were tested for the inhibition of Trichomonas growth at 10 μM with Z' values of >0.5. Hits were rescreened in serial dilution to establish an IC50 concentration. A series of 7-substituted 7-deazaadenosine analogues emerged as highly potent anti-T. vaginalis agents, with EC50 values in the low double digit nanomolar range. These analogues exhibited excellent selectivity indices. Follow-up medicinal chemistry efforts identified an optimal ribofuranose and C7 substituent. Several nucleosides rapidly cleared cultures of T. vaginalis at a concentrations of just 2 × EC50. Preliminary in vivo evaluation in a murine trichomoniasis model (Tritrichomonas foetus) revealed promising activity upon topical administration, validating purine nucleoside analogues as a new class of antitrichomonal agents.

Published
2021

18. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study

Author

Alvarez, Marifé, Andersen, Peter, Angeli, Paolo, Ardèvol, Alba, Arslanow, Anita, Beggiato, Luca, Ben Abdesselam, Zahia, Bennett, Lucy, Boutouria, Bajiha, Brocca, Alessandra, Broquetas, M. Teresa, Caballeria, Llorenç, Calvino, Valeria, Camacho, Judith, Capdevila, Aura, Carol, Marta, Castera, Laurent, Cervera, Marta, Cucchietti, Fernando, de Fuentes, Anna, de Knegt, Rob, de Koning, Harry J, Detlefsen, Sonke, Diaz, Alba, Diéguez Bande, José, Esnault, Vanessa, Fabrellas, Núria, Falcó, Josep Lluis, Fernández, Rosa, Fournier, Céline, Fuentes, Matilde, Galle, Peter, García, Edgar, García-Retortillo, Montserrat, Garrido, Esther, Ginès, Pere, Gordillo Medina, Rosa, Gratacós-Ginès, Jordi, Graupera, Isabel, Grgurevic, Ivica, Guha, Indra Neil, Guix, Eva, Hansen, Johanne Kragh, Harris, Rebecca, Hernández Boluda, Elena, Hernández-Ibañez, Rosario, Hoyo, Jordi, Ikram, Arfan, Incicco, Simone, Israelsen, Mads, Juan, Marta, Juanola, Adrià, Kaiser, Ralf, Kamath, Patrick S, Karlsen, Tom H, Kjærgaard, Maria, Korenjak, Marko, Krag, Aleksander, Krawczyk, Marcin, Laboulaye, Philippe, Lambert, Irina, Lammert, Frank, Langkjær Sørensen, Simon, Laserna-Jiménez, Cristina, Lazaro Pi, Sonia, Ledain, Elsa, Levy, Vincent, Lindvig, Katrine Prier, Llorca, Anne, Londoño, Vanessa, Loyer, Guirec, Ma, Ann T., Madir, Anita, Manns, Michael, Marshall, Denise, Martí, M. Lluïsa, Martínez, Sara, Martínez Sala, Ricard, Masa-Font, Roser, Møller Jensen, Jane, Morillas, Rosa M, Muñoz, Laura, Nadal, Ruth, Napoleone, Laura, Navarrete, JM, Newsome, Phillip N, Nielsen, Vibeke, Pérez, Martina, Pericás-Pulido, Juan Manuel, Piano, Salvatore, Pich, Judit, Pose, Elisa, Presas Escobet, Judit, Reichert, Matthias, Riba, Carlota, Roulot, Dominique, Rubio, Ana Belén, Sánchez-Morata, Maria, Schattenberg, Jörn, Serra-Burriel, Miquel, Serra-Burriel, Feliu, Skovborg Just, Louise, Sonneveld, Milan, Soria, Anna, Stern, Christiane, Such, Patricia, Thiele, Maja, Tonon, Marta, Toran, Pere, Torrejón, Antoni, Tsochatzis, Emmanuel A, van Kleef, Laurens, van Wijngaarden, Paulien, Velázquez, Vanessa, Viu, Ana, Weber, Susanne Nicole, Wildsmith, Tracey, Pera, Guillem, Reichert, Mathias, Pericàs, Juan M, Schattenberg, Jörn M, Tsochatztis, Emmanuel A, Garcia-Retortillo, Montserrat, Hernández, Rosario, Expósito, Carmen, Martínez, Alba, Detlefsen, Sönke, Martini, Andrea, Ma, Ann T, Pich, Judith, Bonfill, Eva, Navarrete, J M, Hernáez, Rubén, Allen, Alina, de Knegt, Robert J, and Wong, Vincent Wai-Sun

Published
2023
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19. Personalized early detection and prevention of breast cancer: ENVISION consensus statement

Author

Pashayan, Nora, Antoniou, Antonis C, Ivanus, Urska, Esserman, Laura J, Easton, Douglas F, French, David, Sroczynski, Gaby, Hall, Per, Cuzick, Jack, Evans, D Gareth, Simard, Jacques, Garcia-Closas, Montserrat, Schmutzler, Rita, Wegwarth, Odette, Pharoah, Paul, Moorthie, Sowmiya, De Montgolfier, Sandrine, Baron, Camille, Herceg, Zdenko, Turnbull, Clare, Balleyguier, Corinne, Rossi, Paolo Giorgi, Wesseling, Jelle, Ritchie, David, Tischkowitz, Marc, Broeders, Mireille, Reisel, Dan, Metspalu, Andres, Callender, Thomas, de Koning, Harry, Devilee, Peter, Delaloge, Suzette, Schmidt, Marjanka K, and Widschwendter, Martin

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Comparative Effectiveness Research, Prevention, Cancer, Aging, Breast Cancer, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Breast Neoplasms, Consensus, Early Detection of Cancer, Evidence-Based Medicine, Female, Genetic Predisposition to Disease, Humans, Mass Screening, Precision Medicine, Oncology and carcinogenesis
Abstract

The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness-implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas.

Published
2020

20. Publisher Correction: Personalized early detection and prevention of breast cancer: ENVISION consensus statement

Author

Pashayan, Nora, Antoniou, Antonis C, Ivanus, Urska, Esserman, Laura J, Easton, Douglas F, French, David, Sroczynski, Gaby, Hall, Per, Cuzick, Jack, Evans, D Gareth, Simard, Jacques, Garcia-Closas, Montserrat, Schmutzler, Rita, Wegwarth, Odette, Pharoah, Paul, Moorthie, Sowmiya, De Montgolfier, Sandrine, Baron, Camille, Herceg, Zdenko, Turnbull, Clare, Balleyguier, Corinne, Rossi, Paolo Giorgi, Wesseling, Jelle, Ritchie, David, Tischkowitz, Marc, Broeders, Mireille, Reisel, Dan, Metspalu, Andres, Callender, Thomas, de Koning, Harry, Devilee, Peter, Delaloge, Suzette, Schmidt, Marjanka K, and Widschwendter, Martin

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Good Health and Well Being, Oncology and carcinogenesis
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

25. LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries

Author

Graupera, Isabel, Thiele, Maja, Ma, Ann T., Serra-Burriel, Miquel, Pich, Judit, Fabrellas, Núria, Caballeria, Llorenç, de Knegt, Robert J., Grgurevic, Ivica, Reichert, Mathias, Roulot, Dominique, Schattenberg, Jörn M., Pericas, Juan M., Angeli, Paolo, Tsochatzis, Emmanuel A., Guha, Indra Neil, Garcia-Retortillo, Montserrat, Morillas, Rosa M., Hernández, Rosario, Hoyo, Jordi, Fuentes, Matilde, Madir, Anita, Juanola, Adrià, Soria, Anna, Juan, Marta, Carol, Marta, Diaz, Alba, Detlefsen, Sönke, Toran, Pere, Pera, Guillem, Fournier, Céline, Llorca, Anne, Newsome, Phillip N., Manns, Michael, de Koning, Harry J., Serra-Burriel, Feliu, Cucchietti, Fernando, Arslanow, Anita, Korenjak, Marko, van Kleef, Laurens, Falcó, Josep Lluis, Kamath, Patrick S., Karlsen, Tom H., Castera, Laurent, Lammert, Frank, Krag, Aleksander, and Ginès, Pere

Published
2022
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27. Early detection of obstructive coronary artery disease in the asymptomatic high-risk population: objectives and study design of the EARLY-SYNERGY trial

Author

Ties, Daan, van Dorp, Paulien, Pundziute, Gabija, van der Aalst, Carlijn M., Gratama, Jan Willem C., Braam, Richard L., Kuijpers, Dirkjan, Lubbers, Daniël D., van der Bilt, Ivo A.C., Westenbrink, B. Daan, Wolcherink, Martijn J. Oude, Doggen, Carine J.M., Išgum, Ivana, Nijveldt, Robin, de Koning, Harry J., Vliegenthart, Rozemarijn, Oudkerk, Matthijs, and van der Harst, Pim

Published
2022
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28. Breast Cancer Screening Using Mammography, Digital Breast Tomosynthesis, and Magnetic Resonance Imaging by Breast Density.

Author

Stout, Natasha K., Miglioretti, Diana L., Su, Yu-Ru, Lee, Christoph I., Abraham, Linn, Alagoz, Oguzhan, de Koning, Harry J., Hampton, John M., Henderson, Louise, Lowry, Kathryn P., Mandelblatt, Jeanne S., Onega, Tracy, Schechter, Clyde B., Sprague, Brian L., Stein, Sarah, Trentham-Dietz, Amy, van Ravesteyn, Nicolien T., Wernli, Karen J., Kerlikowske, Karla, and Tosteson, Anna N. A.

Published
2024
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29. Benign-by-Design SAHA Analogues for Human and Animal Vector-Borne Parasitic Diseases.

Author

Rossi, Michele, Martinengo, Bianca, Diamanti, Eleonora, Salerno, Alessandra, Rizzardi, Nicola, Fato, Romana, Bergamini, Christian, Souza de Oliveira, Andressa, de Araújo Marques Ferreira, Thais, Andrade Holanda, Cleonice, Romeiro, Luiz Antonio Soares, Soeiro, Maria de Nazaré Correia, Nunes, Krislayne, Ferreira de Almeida Fiuza, Ludmila, Meuser Batista, Marcos, Fraga, Carlos A. M., E. A. Alkhalaf, Hamed, Elmahallawy, Ehab Kotb, Ebiloma, Godwin U., and De Koning, Harry P.

Published
2024
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30. Screening

Author

de Koning, Harry, Stronks, Karien, editor, and Burdorf, Alex, editor

Published
2021
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31. The Impact of Model Assumptions on Personalized Lung Cancer Screening Recommendations

Author

ten Haaf, Kevin, primary, de Nijs, Koen, additional, Simoni, Giulia, additional, Alban, Andres, additional, Cao, Pianpian, additional, Sun, Zhuolu, additional, Yong, Jean, additional, Jeon, Jihyoun, additional, Toumazis, Iakovos, additional, Han, Summer S., additional, Gazelle, G. Scott, additional, Kong, Chung Ying, additional, Plevritis, Sylvia K., additional, Meza, Rafael, additional, and de Koning, Harry J., additional

Published
2024
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33. Synthesis, biological, and photophysical studies of molecular rotor-based fluorescent inhibitors of the trypanosome alternative oxidase

Author

Cueto-Díaz, Eduardo J., Ebiloma, Godwin U., Alfayez, Ibrahim A., Ungogo, Marzuq A., Lemgruber, Leandro, González-García, M. Carmen, Giron, Maria D., Salto, Rafael, Fueyo-González, Francisco José, Shiba, Tomoo, González-Vera, Juan A., Ruedas Rama, Maria José, Orte, Angel, de Koning, Harry P., and Dardonville, Christophe

Published
2021
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38. Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis

Author

Hobbs, Brian D, de Jong, Kim, Lamontagne, Maxime, Bossé, Yohan, Shrine, Nick, Artigas, María Soler, Wain, Louise V, Hall, Ian P, Jackson, Victoria E, Wyss, Annah B, London, Stephanie J, North, Kari E, Franceschini, Nora, Strachan, David P, Beaty, Terri H, Hokanson, John E, Crapo, James D, Castaldi, Peter J, Chase, Robert P, Bartz, Traci M, Heckbert, Susan R, Psaty, Bruce M, Gharib, Sina A, Zanen, Pieter, Lammers, Jan W, Oudkerk, Matthijs, Groen, HJ, Locantore, Nicholas, Tal-Singer, Ruth, Rennard, Stephen I, Vestbo, Jørgen, Timens, Wim, Paré, Peter D, Latourelle, Jeanne C, Dupuis, Josée, O'Connor, George T, Wilk, Jemma B, Kim, Woo Jin, Lee, Mi Kyeong, Oh, Yeon-Mok, Vonk, Judith M, de Koning, Harry J, Leng, Shuguang, Belinsky, Steven A, Tesfaigzi, Yohannes, Manichaikul, Ani, Wang, Xin-Qun, Rich, Stephen S, Barr, R Graham, Sparrow, David, Litonjua, Augusto A, Bakke, Per, Gulsvik, Amund, Lahousse, Lies, Brusselle, Guy G, Stricker, Bruno H, Uitterlinden, André G, Ampleford, Elizabeth J, Bleecker, Eugene R, Woodruff, Prescott G, Meyers, Deborah A, Qiao, Dandi, Lomas, David A, Yim, Jae-Joon, Kim, Deog Kyeom, Hawrylkiewicz, Iwona, Sliwinski, Pawel, Hardin, Megan, Fingerlin, Tasha E, Schwartz, David A, Postma, Dirkje S, MacNee, William, Tobin, Martin D, Silverman, Edwin K, Boezen, H Marike, and Cho, Michael H

Subjects
Biological Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Lung, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adult, Aged, Aged, 80 and over, Alleles, Asthma, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Pulmonary Fibrosis, Risk Factors, Smoking, COPDGene Investigators, ECLIPSE Investigators, LifeLines Investigators, SPIROMICS Research Group, International COPD Genetics Network Investigators, UK BiLEVE Investigators, International COPD Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Published
2017

39. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

Author

Natarajan, Pradeep, Bis, Joshua C, Bielak, Lawrence F, Cox, Amanda J, Dörr, Marcus, Feitosa, Mary F, Franceschini, Nora, Guo, Xiuqing, Hwang, Shih-Jen, Isaacs, Aaron, Jhun, Min A, Kavousi, Maryam, Li-Gao, Ruifang, Lyytikäinen, Leo-Pekka, Marioni, Riccardo E, Schminke, Ulf, Stitziel, Nathan O, Tada, Hayato, van Setten, Jessica, Smith, Albert V, Vojinovic, Dina, Yanek, Lisa R, Yao, Jie, Yerges-Armstrong, Laura M, Amin, Najaf, Baber, Usman, Borecki, Ingrid B, Carr, J Jeffrey, Chen, Yii-Der Ida, Cupples, L Adrienne, de Jong, Pim A, de Koning, Harry, de Vos, Bob D, Demirkan, Ayse, Fuster, Valentin, Franco, Oscar H, Goodarzi, Mark O, Harris, Tamara B, Heckbert, Susan R, Heiss, Gerardo, Hoffmann, Udo, Hofman, Albert, Išgum, Ivana, Jukema, J Wouter, Kähönen, Mika, Kardia, Sharon LR, Kral, Brian G, Launer, Lenore J, Massaro, Joe, Mehran, Roxana, Mitchell, Braxton D, Mosley, Thomas H, de Mutsert, Renée, Newman, Anne B, Nguyen, Khanh-Dung, North, Kari E, O'Connell, Jeffrey R, Oudkerk, Matthijs, Pankow, James S, Peloso, Gina M, Post, Wendy, Province, Michael A, Raffield, Laura M, Raitakari, Olli T, Reilly, Dermot F, Rivadeneira, Fernando, Rosendaal, Frits, Sartori, Samantha, Taylor, Kent D, Teumer, Alexander, Trompet, Stella, Turner, Stephen T, Uitterlinden, Andre G, Vaidya, Dhananjay, van der Lugt, Aad, Völker, Uwe, Wardlaw, Joanna M, Wassel, Christina L, Weiss, Stefan, Wojczynski, Mary K, Becker, Diane M, Becker, Lewis C, Boerwinkle, Eric, Bowden, Donald W, Deary, Ian J, Dehghan, Abbas, Felix, Stephan B, Gudnason, Vilmundur, Lehtimäki, Terho, Mathias, Rasika, Mook-Kanamori, Dennis O, Psaty, Bruce M, Rader, Daniel J, Rotter, Jerome I, Wilson, James G, van Duijn, Cornelia M, Völzke, Henry, Kathiresan, Sekar, Peyser, Patricia A, and O'Donnell, Christopher J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease - Coronary Heart Disease, Aging, Human Genome, Atherosclerosis, Cardiovascular, Heart Disease, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Apolipoprotein B-100, Apolipoprotein E2, Asymptomatic Diseases, Black People, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, LDL, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Exome, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Odds Ratio, Oligonucleotide Array Sequence Analysis, Phenotype, Prognosis, Risk Assessment, Risk Factors, Vascular Calcification, White People, carotid intima-media thickness, coronary artery calcification, exome, genome-wide association study, genomics, CHARGE Consortium, carotid intima–media thickness, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundThe burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.Methods and resultsWe studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10-10). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1×10-12) and 1.4% reduced carotid intima-media thickness (P=4×10-14) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1×10-11).ConclusionsExome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.

Published
2016

41. Breast Cancer Screening in Georgia:Choosing the Most Optimal and Cost-Effective Strategy

Author

Irzaldy, Abyan, Gvamichava, Rema, Beruchashvili, Tina, Sturua, Lela, van Ravesteyn, Nicolien T., de Koning, Harry J., Heijnsdijk, Eveline A.M., Irzaldy, Abyan, Gvamichava, Rema, Beruchashvili, Tina, Sturua, Lela, van Ravesteyn, Nicolien T., de Koning, Harry J., and Heijnsdijk, Eveline A.M.

Abstract

Objectives: To define the optimal and cost-effective breast cancer screening strategy for Georgia. Methods: We used the Microsimulation Screening Analysis-Breast (MISCAN-Breast) model that has been adapted to the Georgian situation to evaluate 736 mammography screening strategies varied by interval (biennial and triennial), starting ages (40-60 years), stopping ages (64-84 years), and screening modality (with and without clinical breast examination [CBE]). Quality-adjusted life-years (QALYs) and additional cost (healthcare perspective) compared with no screening per 1000 women were calculated with 3% discount. Major uncertainties (eg, costs) are addressed as sensitivity analyses. Results: Strategies using a combination of mammography and CBE yielded in substantially higher costs with minimal differences in outcomes compared with mammography-only strategies. The current screening strategy, biennial mammography screening from the age of 40 until 70 years with CBE, is close to the frontier line but requires high additional cost given the QALY gains (€16 218/QALY), well above the willingness-to-pay threshold of €12 720. The optimal strategy in Georgia would be triennial mammography-only screening from age 45 to 66 years with an incremental cost-effectiveness ratio of €12 507. Conclusions: Biennial screening strategies are resource-intensive strategies and may not be feasible for Georgia. By switching to triennial mammography-only strategy from the age of 45 until 66 years, it is possible to offer screening to more eligible women while still gaining substantial screening benefits. This is to address capacity issues which is a common barrier for many Eastern European countries.

Published
2024

42. Cost-effectiveness of risk-based low-dose computed tomography screening for lung cancer in Switzerland

Author

Tomonaga, Yuki, de Nijs, Koen, Bucher, Heiner C., de Koning, Harry, ten Haaf, Kevin, Tomonaga, Yuki, de Nijs, Koen, Bucher, Heiner C., de Koning, Harry, and ten Haaf, Kevin

Abstract

Throughout Europe, computed tomography (CT) screening for lung cancer is in a phase of clinical implementation or reimbursement evaluation. To efficiently select individuals for screening, the use of lung cancer risk models has been suggested, but their incremental (cost-)effectiveness relative to eligibility based on pack-year criteria has not been thoroughly evaluated for a European setting. We evaluate the cost-effectiveness of pack-year and risk-based screening (PLCOm2012 model-based) strategies for Switzerland, which aided in informing the recommendations of the Swiss Cancer Screening Committee (CSC). We use the MISCAN (MIcrosimulation SCreening ANalysis)-Lung model to estimate benefits and harms of screening among individuals born 1940 to 1979 in Switzerland. We evaluate 1512 strategies, differing in the age ranges employed for screening, the screening interval and the strictness of the smoking requirements. We estimate risk-based strategies to be more cost-effective than pack-year-based screening strategies. The most efficient strategy compliant with CSC recommendations is biennial screening for ever-smokers aged 55 to 80 with a 1.6% PLCOm2012 risk. Relative to no screening this strategy is estimated to reduce lung cancer mortality by 11.0%, with estimated costs per Quality-Adjusted Life-Year (QALY) gained of €19 341, and a €1.990 billion 15-year budget impact. Biennial screening ages 55 to 80 for those with 20 pack-years shows a lower mortality reduction (10.5%) and higher cost per QALY gained (€20 869). Despite model uncertainties, our estimates suggest there may be cost-effective screening policies for Switzerland. Risk-based biennial screening ages 55 to 80 for those with ≥1.6% PLCOm2012 risk conforms to CSC recommendations and is estimated to be more efficient than pack-year-based alternatives.

Published
2024

43. The Impact of Model Assumptions on Personalized Lung Cancer Screening Recommendations

Author

Ten Haaf, Kevin, de Nijs, Koen, Simoni, Giulia, Alban, Andres, Cao, Pianpian, Sun, Zhuolu, Yong, Jean, Jeon, Jihyoun, Toumazis, Iakovos, Han, Summer S, Gazelle, G Scott, Kong, Chung Ying, Plevritis, Sylvia K, Meza, Rafael, de Koning, Harry J, Ten Haaf, Kevin, de Nijs, Koen, Simoni, Giulia, Alban, Andres, Cao, Pianpian, Sun, Zhuolu, Yong, Jean, Jeon, Jihyoun, Toumazis, Iakovos, Han, Summer S, Gazelle, G Scott, Kong, Chung Ying, Plevritis, Sylvia K, Meza, Rafael, and de Koning, Harry J

Abstract

BACKGROUND: Recommendations regarding personalized lung cancer screening are being informed by natural-history modeling. Therefore, understanding how differences in model assumptions affect model-based personalized screening recommendations is essential.DESIGN: Five Cancer Intervention and Surveillance Modeling Network (CISNET) models were evaluated. Lung cancer incidence, mortality, and stage distributions were compared across 4 theoretical scenarios to assess model assumptions regarding 1) sojourn times, 2) stage-specific sensitivities, and 3) screening-induced lung cancer mortality reductions. Analyses were stratified by sex and smoking behavior.RESULTS: Most cancers had sojourn times <5 y (model range [MR]; lowest to highest value across models: 83.5%-98.7% of cancers). However, cancer aggressiveness still varied across models, as demonstrated by differences in proportions of cancers with sojourn times <2 y (MR: 42.5%-64.6%) and 2 to 4 y (MR: 28.8%-43.6%). Stage-specific sensitivity varied, particularly for stage I (MR: 31.3%-91.5%). Screening reduced stage IV incidence in most models for 1 y postscreening; increased sensitivity prolonged this period to 2 to 5 y. Screening-induced lung cancer mortality reductions among lung cancers detected at screening ranged widely (MR: 14.6%-48.9%), demonstrating variations in modeled treatment effectiveness of screen-detected cases. All models assumed longer sojourn times and greater screening-induced lung cancer mortality reductions for women. Models assuming differences in cancer epidemiology by smoking behaviors assumed shorter sojourn times and lower screening-induced lung cancer mortality reductions for heavy smokers.CONCLUSIONS: Model-based personalized screening recommendations are primarily driven by assumptions regarding sojourn times (favoring longer intervals for groups more likely to develop less aggressive cancers), sensitivity (higher sensitivities favoring longer intervals), and s

Published
2024

45. Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age

Author

van der Beek, A., Otte, J.A., Wiersma, Tj., Masclee, A.A.M., van Bergeijk, J., Meijer, G., de Graaf, E.J.R., van Grevenstein, W.M.U., Frasa, M., Jacobs, L.H.J., Stoker, J., Vink, G., Elferink, M.A., Toes-Zoutendijk, Esther, Kooyker, Arthur I., Dekker, Evelien, Spaander, Manon C.W., Opstal-van Winden, Annemieke W.J., Ramakers, Christian, Buskermolen, Maaike, van Vuuren, Anneke J., Kuipers, Ernst J., van Kemenade, Folkert J., Velthuysen, Marie-Louise F., Thomeer, Maarten G.J., van Veldhuizen, Harriët, van Ballegooijen, Marjolein, Nagtegaal, Iris D., de Koning, Harry J., van Leerdam, Monique E., and Lansdorp-Vogelaar, Iris

Published
2020
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49. Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

Author

Miglioretti, Diana L, Lange, Jane, van den Broek, Jeroen J, Lee, Christoph I, van Ravesteyn, Nicolien T, Ritley, Dominique, Kerlikowske, Karla, Fenton, Joshua J, Melnikow, Joy, de Koning, Harry J, and Hubbard, Rebecca A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Prevention, Clinical Research, Health Services, Biomedical Imaging, Breast Cancer, Good Health and Well Being, Adult, Aged, Breast, Breast Neoplasms, Computer Simulation, Early Detection of Cancer, Female, Humans, Incidence, Mammography, Mass Screening, Middle Aged, Neoplasms, Radiation-Induced, Radiation Dosage, Risk Factors, United States, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundEstimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results.ObjectiveTo estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women.Design2 simulation-modeling approaches.SettingU.S. population.PatientsWomen aged 40 to 74 years.InterventionAnnual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years.MeasurementsLifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened.ResultsAnnual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold.LimitationLife-years lost from radiation-induced breast cancer could not be estimated.ConclusionRadiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer.Primary funding sourceAgency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

Published
2016

50. Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies.

Author

Mandelblatt, Jeanne S, Stout, Natasha K, Schechter, Clyde B, van den Broek, Jeroen J, Miglioretti, Diana L, Krapcho, Martin, Trentham-Dietz, Amy, Munoz, Diego, Lee, Sandra J, Berry, Donald A, van Ravesteyn, Nicolien T, Alagoz, Oguzhan, Kerlikowske, Karla, Tosteson, Anna NA, Near, Aimee M, Hoeffken, Amanda, Chang, Yaojen, Heijnsdijk, Eveline A, Chisholm, Gary, Huang, Xuelin, Huang, Hui, Ergun, Mehmet Ali, Gangnon, Ronald, Sprague, Brian L, Plevritis, Sylvia, Feuer, Eric, de Koning, Harry J, and Cronin, Kathleen A

Subjects
Breast, Humans, Breast Neoplasms, False Positive Reactions, Mammography, Mass Screening, Incidence, Risk Assessment, Age Factors, Comorbidity, Time Factors, Computer Simulation, Adult, Aged, Middle Aged, United States, Female, Early Detection of Cancer, Prevention, Health Services, Cancer, Clinical Research, Breast Cancer, Biomedical Imaging, Good Health and Well Being, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundControversy persists about optimal mammography screening strategies.ObjectiveTo evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer.DesignCollaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality.SettingUnited States.PatientsAverage-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity.InterventionEight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years.MeasurementsBenefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens.ResultsBiennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years.LimitationOther imaging technologies, polygenic risk, and nonadherence were not considered.ConclusionBiennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening.Primary funding sourceNational Institutes of Health.

Published
2016

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