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3. Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Author

Macauda, Angelica, Clay-Gilmour, Alyssa, Hielscher, Thomas, Hildebrandt, Michelle, Kruszewski, Marcin, Orlowski, Robert, Kumar, Shaji, Ziv, Elad, Orciuolo, Enrico, Brown, Elizabeth, Försti, Asta, Waller, Rosalie, Machiela, Mitchell, Chanock, Stephen, Camp, Nicola, Rymko, Marcin, Raźny, Małgorzata, Cozen, Wendy, Várkonyi, Judit, Piredda, Chiara, Pelosini, Matteo, Belachew, Alem, Subocz, Edyta, Hemminki, Kari, Rybicka-Ramos, Malwina, Giles, Graham, Milne, Roger, Hofmann, Jonathan, Zaucha, Jan, Vangsted, Annette, Goldschmidt, Hartmut, Rajkumar, S, Tomczak, Waldemar, Sainz, Juan, Butrym, Aleksandra, Watek, Marzena, Iskierka-Jazdzewska, Elżbieta, Buda, Gabriele, Robinson, Dennis, Jurczyszyn, Artur, Dudziński, Marek, Martinez-Lopez, Joaquin, Sinnwell, Jason, Slager, Susan, Jamroziak, Krzysztof, Reis, Rui, Weinhold, Niels, Bhatti, Parveen, Carvajal-Carmona, Luis, Zawirska, Daria, Norman, Aaron, Mazur, Grzegorz, Berndt, Sonja, Campa, Daniele, Vachon, Celine, and Canzian, Federico

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multiple Myeloma, Polymorphism, Single Nucleotide, Risk Factors
Abstract

BACKGROUND: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. METHODS: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. RESULTS: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. CONCLUSIONS: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. IMPACT: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.

Published
2022

4. Mass spectrometry–based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma

Author

Kubicki, Tadeusz, Dytfeld, Dominik, Barnidge, David, Sakrikar, Dhananjay, Przybyłowicz-Chalecka, Anna, Jamroziak, Krzysztof, Robak, Paweł, Czyż, Jarosław, Tyczyńska, Agata, Druzd-Sitek, Agnieszka, Giannopoulos, Krzysztof, Wróbel, Tomasz, Nowicki, Adam, Szczepaniak, Tomasz, Łojko-Dankowska, Anna, Matuszak, Magdalena, Gil, Lidia, Puła, Bartosz, Szukalski, Łukasz, Końska, Agnieszka, Zaucha, Jan Maciej, Walewski, Jan, Mikulski, Damian, Czabak, Olga, Robak, Tadeusz, Jiang, Ken, Cooperrider, Jennifer H., Jakubowiak, Andrzej J., and Derman, Benjamin A.

Published
2024
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5. Clinical efficacy and tolerability of venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia—a real-world analysis of the Polish Adult Leukemia Study Group

Author

Soboń, Anita, Drozd-Sokołowska, Joanna, Paszkiewicz-Kozik, Ewa, Popławska, Lidia, Morawska, Marta, Tryc-Szponder, Jagoda, Bołkun, Łukasz, Rybka, Justyna, Pruszczyk, Katarzyna, Juda, Adrian, Majeranowski, Alan, Iskierka-Jażdżewska, Elżbieta, Steckiewicz, Paweł, Wdowiak, Kamil, Budziszewska, Bożena, Jamroziak, Krzysztof, Hus, Iwona, Lech-Marańda, Ewa, and Puła, Bartosz

Published
2023
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7. Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Author

Piccardi, Margherita, Gentiluomo, Manuel, Bertoncini, Stefania, Pezzilli, Raffaele, Erőss, Bálint, Bunduc, Stefania, Uzunoglu, Faik G., Talar-Wojnarowska, Renata, Vanagas, Tomas, Sperti, Cosimo, Oliverius, Martin, Aoki, Mateus Nóbrega, Ermini, Stefano, Hussein, Tamás, Boggi, Ugo, Jamroziak, Krzysztof, Maiello, Evaristo, Morelli, Luca, Vodickova, Ludmila, Di Franco, Gregorio, Landi, Stefano, Szentesi, Andrea, Lovecek, Martin, Puzzono, Marta, Tavano, Francesca, van Laarhoven, Hanneke W. M., Zerbi, Alessandro, Mohelnikova-Duchonova, Beatrice, Stocker, Hannah, Costello, Eithne, Capurso, Gabriele, Ginocchi, Laura, Lawlor, Rita T., Vanella, Giuseppe, Bazzocchi, Francesca, Izbicki, Jakob R., Latiano, Anna, Bueno-de-Mesquita, Bas, Ponz de Leon Pisani, Ruggero, Schöttker, Ben, Soucek, Pavel, Hegyi, Péter, Gazouli, Maria, Hackert, Thilo, Kupcinskas, Juozas, Poskiene, Lina, Tacelli, Matteo, Roth, Susanne, Carrara, Silvia, Perri, Francesco, Hlavac, Viktor, Theodoropoulos, George E., Busch, Olivier R., Mambrini, Andrea, van Eijck, Casper H. J., Arcidiacono, Paolo, Scarpa, Aldo, Pasquali, Claudio, Basso, Daniela, Lucchesi, Maurizio, Milanetto, Anna Caterina, Neoptolemos, John P., Cavestro, Giulia Martina, Janciauskas, Dainius, Chen, Xuechen, Chammas, Roger, Goetz, Mara, Brenner, Hermann, Archibugi, Livia, Dannemann, Michael, Canzian, Federico, Tofanelli, Sergio, and Campa, Daniele

Published
2023
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8. The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years’ experience of association studies to understand the genetic architecture of pancreatic cancer

Author

Campa, Daniele, Gentiluomo, Manuel, Stein, Angelika, Aoki, Mateus Nóbrega, Oliverius, Martin, Vodičková, Ludmila, Jamroziak, Krzysztof, Theodoropoulos, George, Pasquali, Claudio, Greenhalf, William, Arcidiacono, Paolo Giorgio, Uzunoglu, Faik, Pezzilli, Raffaele, Luchini, Claudio, Puzzono, Marta, Loos, Martin, Giaccherini, Matteo, Katzke, Verena, Mambrini, Andrea, Kiudeliene, Edita, Federico, Kauffmann Emanuele, Johansen, Julia, Hussein, Tamás, Mohelnikova-Duchonova, Beatrice, van Eijck, Casper H.J., Brenner, Hermann, Farinella, Riccardo, Pérez, Juan Sainz, Lovecek, Martin, Büchler, Markus W., Hlavac, Viktor, Izbicki, Jakob R., Hackert, Thilo, Chammas, Roger, Zerbi, Alessandro, Lawlor, Rita, Felici, Alessio, Götz, Mara, Capurso, Gabriele, Ginocchi, Laura, Gazouli, Maria, Kupcinskas, Juozas, Cavestro, Giulia Martina, Vodicka, Pavel, Moz, Stefania, Neoptolemos, John P., Kunovsky, Lumir, Bojesen, Stig E., Carrara, Silvia, Gioffreda, Domenica, Morkunas, Egidijus, Abian, Olga, Bunduc, Stefania, Basso, Daniela, Boggi, Ugo, Wlodarczyk, Barbara, Szentesi, Andrea, Vanella, Giuseppe, Chen, Inna, Bijlsma, Maarten F., Kiudelis, Vytautas, Landi, Stefano, Schöttker, Ben, Corradi, Chiara, Giese, Nathalia, Kaaks, Rudolf, Peduzzi, Giulia, Hegyi, Péter, Morelli, Luca, Furbetta, Niccolò, Soucek, Pavel, Latiano, Anna, Talar-Wojnarowska, Renata, Lindgaard, Sidsel C., Dijk, Frederike, Milanetto, Anna Caterina, Tavano, Francesca, Cervena, Klara, Erőss, Bálint, Testoni, Sabrina G., Verhagen-Oldenampsen, Judith H.E., Małecka-Wojciesko, Ewa, Costello, Eithne, Salvia, Roberto, Maiello, Evaristo, Ermini, Stefano, Sperti, Cosimo, Holleczek, Bernd, Perri, Francesco, Skieceviciene, Jurgita, Archibugi, Livia, Lucchesi, Maurizio, Rizzato, Cosmeri, and Canzian, Federico

Published
2023
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10. Pneumonia in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens: A Real-World Analysis of the Polish Adult Leukemia Group (PALG).

Author

Kalicińska, Elżbieta, Jabłonowska-Babij, Paula, Morawska, Marta, Iskierka-Jażdżewska, Elżbieta, Drozd-Sokołowska, Joanna, Paszkiewicz-Kozik, Ewa, Szukalski, Łukasz, Strzała, Judyta, Gosik, Urszula, Dębski, Jakub, Andrasiak, Iga, Skotny, Anna, Jamroziak, Krzysztof, and Wróbel, Tomasz

Subjects
THERAPEUTIC use of antineoplastic agents, RISK factors of pneumonia, PNEUMONIA, CHRONIC lymphocytic leukemia, COMBINATION drug therapy, RISK assessment, RESEARCH funding, RITUXIMAB, MULTIVARIATE analysis, DESCRIPTIVE statistics, ODDS ratio, RESEARCH, STATISTICS, PROGRESSION-free survival, COMPARATIVE studies, CONFIDENCE intervals, OVERALL survival, ADULTS
Abstract

Simple Summary: This multicenter study assessed the incidence of pneumonia and its impact on survival in 322 patients with chronic lymphocytic leukemia (CLL) who were treated with venetoclax-based regimens. In real-world settings, patients with CLL who are treated with venetoclax-based regimens are at a higher risk of pneumonia, especially patients with R/R CLL who are treated with venetoclax in combination with rituximab compared to registration trials. Pneumonia has a negative impact on overall survival (OS) in patients with CLL who are receiving venetoclax-based therapy. However, in patients treated with first-line venetoclax and obinutuzumab, despite the high burden of comorbidities, the occurrence of pneumonia does not affect OS. Key risk factors for shorter event-free survival (EFS) in patients with CLL who were treated with venetoclax-based regimens included chronic obstructive pulmonary disease/asthma, spleen enlargement, elevated creatinine levels, and severe anemia; we identified a subgroup of patients at a high risk of pneumonia who particularly required anti-infective prophylaxis, appropriate treatment of underlying diseases, and close monitoring. Neutropenia, although common (59%), was not linked to an increased risk of pneumonia. These findings highlight the important issue of pneumonia and its impact on OS in the CLL patient population treated with venetoclax-based regimens, especially in patients following earlier lines of treatment, with R/R disease. Background/Objectives: Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections that can affect their clinical outcomes. Aims: The aims of this study were to assess the following: (1) the incidence of pneumonia in CLL patients treated with venetoclax-based regimens in a real-world setting, (2) the risk factors for event-free survival (EFS), and (3) overall survival (OS). Methods: This multicenter study included 322 patients from eight centers. Univariable and multivariable analyses (MVA) were performed, with the development of pneumonia during venetoclax-based treatment and OS as outcomes. Results: The most common complication was neutropenia (59%). During treatment with venetoclax-based regimens, 66 (20%) patients developed pneumonia—50 (23%) patients in the rituximab-plus-venetoclax (R-VEN) group and 13 (16%) patients in the obinutuzumab-plus-venetoclax (O-VEN) group (p = 0.15). Chronic obstructive pulmonary disease (COPD)/asthma, splenomegaly, elevated creatinine, and anemia < 8 g/dL were the risk factors for EFS in MVA (HR = 2.08, 95%CI 1.16–3.74, p = 0.014; HR 1.73, 95%CI 1.08–2.78, p = 0.02; HR 2.13, 95%CI 1.10–4.11, p = 0.03, HR 3.58, 95%CI 2.18–5.89, p < 0.001, respectively). Relapsed/refractory (R/R) CLL patients treated with R-VEN with pneumonia had worse OS than those without (p < 0.001). In patients treated with O-VEN, median OS did not differ between patients with and without pneumonia (p = 0.45). Conclusions: Our real-world study showed that pneumonia during venetoclax treatment occurs more frequently than reported in registration trials and has a negative impact on OS, especially in patients with R/R CLL who are treated with R-VEN. Neutropenia is not a risk factor for pneumonia. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Mechanisms of resistance to venetoclax in hematologic malignancies.

Author

Zielonka, Klaudia and Jamroziak, Krzysztof

Subjects
CHRONIC lymphocytic leukemia, ACUTE myeloid leukemia, CHRONIC myeloid leukemia, MULTIPLE myeloma, HEMATOLOGIC malignancies
Abstract

Venetoclax, a BH3 mimetic, is a novel targeted anti-cancer drug with a unique mechanism of action leading to the execution of apoptosis through inhibition of the Bcl-2 protein. The development of venetoclax has revolutionized the treatment paradigm of several hematologic malignancies, including treatment-naïve and relapsed or refractory chronic lymphocytic leukemia (CLL) as well as acute myeloid leukemia (AML) in unfit patients. However, despite the high effectiveness of venetoclax in these diseases, some patients, as in the case with other targeted therapies, develop primary or secondary resistance to the drug. Various mechanisms contributing to the resistance to venetoclax have been elucidated, including selection of mutations in the BCL-2 binding groove which decrease affinity to venetoclax, or compensatory overexpression of anti-apoptotic proteins such as MCL-1. Moreover, alterations in cell metabolism and signaling pathways like MAPK or ERK activation have also been reported, suggesting the resistance to venetoclax is highly complex and involves multiple pathways. This review aimed to describe the mechanisms of resistance to venetoclax in AML, CLL, multiple myeloma, and other hematologic malignancies, as well as to propose a perspective to circumvent it. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Comparison of Abrasive Wear Resistance of Hardox Steel and Hadfield Cast Steel.

Author

Zemlik, Martyna, Konat, Łukasz, Leśny, Kacper, and Jamroziak, Krzysztof

Subjects
BORON steel, CAST steel, STEEL founding, COLD working of metals, WEAR resistance
Abstract

Among the materials used for components subjected to abrasive wear, chromium cast iron, hardfaced layers, martensitic steels and Hadfield steel should be singled out. Each of these types of materials exhibits a different morphology of structure and strength properties. Hadfield steel, characterized by an austenitic microstructure, shows the ability to strengthen the subsurface layers by cold work, while maintaining a ductile core. Hardox steels belong to the group of low-alloy martensitic boron steels. However, it should be noted that increasing hardness does not always translate into low wear values due to a change in the nature of wear. In view of the above, the authors decided to subject selected Hardox steels and Hadfield cast steels in the post-operational condition to abrasive wear tests in the presence of loose abrasive. The study showed that Hardox Extreme steel exhibits the highest resistance to abrasive wear (value of the coefficient kb is equal to 1.39). In the case of Hadfield steel, the recorded values are slightly lower (kb = 1.32 and 1.33), while the above ratios remain higher compared to Hardox 600 and Hardox 500 steels. The main wear mechanism of high-manganese steels is microploughing, plastic deformation and breakouts of larger fragments of material. In the case of Hardox 450 and Hardox 500 steels, the predominant wear mechanisms are microploughing and breaking out of material fragments. As the hardness of the steel increases, the proportion of wear by microcutting and scratching predominates. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Measurable Residual Disease in Hematological Cancers.

Author

Jamroziak, Krzysztof and Puła, Bartosz

Subjects
*RISK assessment, *SERIAL publications, *HEMATOLOGIC malignancies, *CANCER patient medical care, *CARCINOGENESIS, *MOLECULAR biology, *ADVERSE health care events, *GENETIC mutation, *INDIVIDUALIZED medicine
Published
2024
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14. A polygenic risk score for multiple myeloma risk prediction

Author

Canzian, Federico, Piredda, Chiara, Macauda, Angelica, Zawirska, Daria, Andersen, Niels Frost, Nagler, Arnon, Zaucha, Jan Maciej, Mazur, Grzegorz, Dumontet, Charles, Wątek, Marzena, Jamroziak, Krzysztof, Sainz, Juan, Várkonyi, Judit, Butrym, Aleksandra, Beider, Katia, Abildgaard, Niels, Lesueur, Fabienne, Dudziński, Marek, Vangsted, Annette Juul, Pelosini, Matteo, Subocz, Edyta, Petrini, Mario, Buda, Gabriele, Raźny, Małgorzata, Gemignani, Federica, Marques, Herlander, Orciuolo, Enrico, Kadar, Katalin, Jurczyszyn, Artur, Druzd-Sitek, Agnieszka, Vogel, Ulla, Andersen, Vibeke, Reis, Rui Manuel, Suska, Anna, Avet-Loiseau, Hervé, Kruszewski, Marcin, Tomczak, Waldemar, Rymko, Marcin, Minvielle, Stephane, and Campa, Daniele

Published
2022
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15. Health-related quality of life in patients with multiple myeloma treated in the phase 3 ATLAS trial of post-transplant maintenance with carfilzomib, lenalidomide, dexamethasone or lenalidomide alone

Author

Kubicki, Tadeusz, primary, Jamroziak, Krzysztof, additional, Robak, Paweł, additional, Czyż, Jarosław, additional, Tyczyńska, Agata, additional, Druzd-Sitek, Agnieszka, additional, Giannopoulos, Krzysztof, additional, Wróbel, Tomasz, additional, Nowicki, Adam, additional, Szczepaniak, Tomasz, additional, Łojko-Dankowska, Anna, additional, Matuszak, Magdalena, additional, Gil, Lidia, additional, Puła, Bartosz, additional, Szukalski, Łukasz, additional, Końska, Agnieszka, additional, Zaucha, Jan M., additional, Walewski, Jan, additional, Mikulski, Damian, additional, Czabak, Olga, additional, Robak, Tadeusz, additional, Kruk-Kwapisz, Dorota, additional, Derman, Benjamin A., additional, Major, Ajay, additional, Jakubowiak, Andrzej J., additional, and Dytfeld, Dominik, additional

Published
2024
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17. High response rates with single-agent belantamab mafodotin in relapsed systemic AL amyloidosis

Author

Khwaja, Jahanzaib, Bomsztyk, Joshua, Mahmood, Shameem, Wisniowski, Brendan, Shah, Raakhee, Tailor, Anish, Yong, Kwee, Popat, Rakesh, Rabin, Neil, Kyriakou, Charalampia, Sive, Jonathan, Esposti, Simona Degli, Larkin, Daniel F. P., Worthington, Sarah, Hart, Alyse, Dowling, Emma, Correia, Nuno, Bygrave, Ceri, Rydzewski, Andrzej, Jamroziak, Krzysztof, and Wechalekar, Ashutosh D.

Published
2022
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19. Numerical Analysis of Stabilization of a Horse's Third Metacarpal Bone Fracture for Prediction of the Possibility of Bone Union.

Author

Słowiński, Jakub, Roszak, Maciej, Krawiec, Karina, Henklewski, Radomir, and Jamroziak, Krzysztof

Subjects
FRACTURE mechanics, LEG injuries, COMPACT bone, SPORTS participation, FINITE element method
Abstract

Horses have been companions of people for thousands of years. Areas in which humans use these animals include, for example, transport, participation in sports competitions, or during rehabilitation (hippotherapy). Unfortunately, injuries such as lower limb fracture very often require euthanasia due to the significant difficulties in conducting fracture therapy/repair. Therefore, there are still many possibilities for the improvement of existing treatments. The aim of the study was to conduct a numerical analysis enabling the prediction of bone union of the third metacarpal bone of a horse. The loading conditions and type of fracture were based on a pony weighing 120 kg; however, research on a live animal was not the purpose of this study. Numerical studies were carried out for three different methods of stabilization using bone plates in the Ansys program (lateral, anterior, and lateral–anterior stabilization). An algorithm based on the Carter model was used to predict bone union, while linear-coupled models were used to describe the behaviour of materials. The authors also performed dynamic analyses in the Abaqus/Explicit program to determine the maximum speed at which the horse could move so that the fracture would not deepen. For dynamic analyses, the authors used nonlinear models—Johnson–Cook in the case of the 316L surgical steel material and cortical bone. Material failure was described using the Johnson–Cook failure model for steel and the limit strain model for cortical bone. A series of numerical simulations allowed to determine the direction of bone union building, and the most favourable case of stabilization was determined. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.

Author

Dean, Eric, Hu, Donglei, Martino, Alessandro, Serie, Daniel, Curtin, Karen, Campa, Daniele, Aftab, Blake, Bracci, Paige, Buda, Gabriele, Zhao, Yi, Caswell-Jin, Jennifer, Diasio, Robert, Dumontet, Charles, Dudziński, Marek, Greenberg, Alexandra, Huntsman, Scott, Jamroziak, Krzysztof, Jurczyszyn, Artur, Kumar, Shaji, Atanackovic, Djordje, Glenn, Martha, Cannon-Albright, Lisa, Jones, Brandt, Lee, Adam, Marques, Herlander, Martin, Thomas, Martinez-Lopez, Joaquin, Rajkumar, Vincent, Sainz, Juan, Vangsted, Annette, Wątek, Marzena, Wolf, Jeffrey, Slager, Susan, Camp, Nicola, Canzian, Federico, Vachon, Celine, Ziv, Elad, and Fejerman, Laura

Subjects
Chromosomes, Human, Pair 16, Genome-Wide Association Study, Humans, Kaplan-Meier Estimate, Multiple Myeloma, Polymorphism, Single Nucleotide
Abstract

Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 × 10(-10)). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0.044). Using publicly available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival. Polymorphisms at the FOPNL locus are associated with survival among MM patients.

Published
2015

22. Health-related quality of life in patients with multiple myeloma treated in the phase 3 ATLAS trial of post-transplant maintenance with carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone.

Author

Kubicki, Tadeusz, Jamroziak, Krzysztof, Robak, Paweł, Czyż, Jarosław, Tyczyńska, Agata, Druzd-Sitek, Agnieszka, Giannopoulos, Krzysztof, Wróbel, Tomasz, Nowicki, Adam, Szczepaniak, Tomasz, Łojko-Dankowska, Anna, Matuszak, Magdalena, Gil, Lidia, Puła, Bartosz, Szukalski, Łukasz, Końska, Agnieszka, Zaucha, Jan M., Walewski, Jan, Mikulski, Damian, and Czabak, Olga

Published
2024
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23. Expert opinion on use of acalabrutinib for chronic lymphocytic leukemia treatment.

Author

Puła, Bartosz, Iskierka-Jażdżewska, Elżbieta, Jamroziak, Krzysztof, Giannopoulos, Krzysztof, Wróbel, Tomasz, Robak, Tadeusz, and Hus, Iwona

Subjects
CHRONIC lymphocytic leukemia, BRUTON tyrosine kinase, PROTEIN-tyrosine kinase inhibitors, CARDIOTOXICITY
Abstract

Bruton's tyrosine kinase inhibitors (BTKis) have become one of the most vital drugs in the treatment of patients with chronic lymphocytic leukemia (CLL). BTKis are currently a well-established therapy for treatment-naïve, as well as relapsed or refractory, cases. BTKis have been shown to be crucial in the treatment of high-risk CLL patients bearing TP53 aberrations or characterized by the unmutated status of the immunoglobulin heavy-chain variable region (IGHV) gene. Ibrutinib was the first-in-class BTK inhibitor; however, despite its therapeutic potential, it is also characterized by specific adverse events, including hypertension, increased bleeding risk, cardiac toxicity, and skin changes. Although the next generation of BTKis was shown to be more specific, this adverse event profile is regarded currently as class--specific. In this review, we discuss the current status of acalabrutinib, a second-generation BTKi. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Sudden central vision loss in a young patient with chronic myeloid leukemia.

Author

Jasiński, Marcin, Krajewski, Przemysław, Paszkowska-Kowalewska, Małgorzata, and Jamroziak, Krzysztof

Subjects
CHRONIC myeloid leukemia, VISION disorders, CHRONIC leukemia
Abstract

The article presents a case study of a 20-year-old female patient diagnosed with chronic myeloid leukemia (CML) who developed sudden central vision loss in her right eye during treatment for hyperleukocytosis. It highlights the importance of early ophthalmologic evaluation in CML patients with high white blood cell counts, as the patient's vision loss was linked to leukostasis, with findings such as retinal hemorrhages, optic disc swelling, and tortuous retinal vessels.

Published
2024
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27. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author

Pertesi, Maroulio, Vallée, Maxime, Wei, Xiaomu, Revuelta, Maria V., Galia, Perrine, Demangel, Delphine, Oliver, Javier, Foll, Matthieu, Chen, Siwei, Perrial, Emeline, Garderet, Laurent, Corre, Jill, Leleu, Xavier, Boyle, Eileen M., Decaux, Olivier, Rodon, Philippe, Kolb, Brigitte, Slama, Borhane, Mineur, Philippe, Voog, Eric, Le Bris, Catherine, Fontan, Jean, Maigre, Michel, Beaumont, Marie, Azais, Isabelle, Sobol, Hagay, Vignon, Marguerite, Royer, Bruno, Perrot, Aurore, Fuzibet, Jean-Gabriel, Dorvaux, Véronique, Anglaret, Bruno, Cony-Makhoul, Pascale, Berthou, Christian, Desquesnes, Florence, Pegourie, Brigitte, Leyvraz, Serge, Mosser, Laurent, Frenkiel, Nicole, Augeul-Meunier, Karine, Leduc, Isabelle, Leyronnas, Cécile, Voillat, Laurent, Casassus, Philippe, Mathiot, Claire, Cheron, Nathalie, Paubelle, Etienne, Moreau, Philippe, Bignon, Yves–Jean, Joly, Bertrand, Bourquard, Pascal, Caillot, Denis, Naman, Hervé, Rigaudeau, Sophie, Marit, Gérald, Macro, Margaret, Lambrecht, Isabelle, Cliquennois, Manuel, Vincent, Laure, Helias, Philippe, Avet-Loiseau, Hervé, Moreno, Victor, Reis, Rui Manuel, Varkonyi, Judit, Kruszewski, Marcin, Vangsted, Annette Juul, Jurczyszyn, Artur, Zaucha, Jan Maciej, Sainz, Juan, Krawczyk-Kulis, Malgorzata, Wątek, Marzena, Pelosini, Matteo, Iskierka-Jażdżewska, Elzbieta, Grząśko, Norbert, Martinez-Lopez, Joaquin, Jerez, Andrés, Campa, Daniele, Buda, Gabriele, Lesueur, Fabienne, Dudziński, Marek, García-Sanz, Ramón, Nagler, Arnon, Rymko, Marcin, Jamroziak, Krzysztof, Butrym, Aleksandra, Canzian, Federico, Obazee, Ofure, Nilsson, Björn, Klein, Robert J., Lipkin, Steven M., McKay, James D., and Dumontet, Charles

Published
2019
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28. Genetically determined telomere length and multiple myeloma risk and outcome

Author

Giaccherini, Matteo, Macauda, Angelica, Orciuolo, Enrico, Rymko, Marcin, Gruenpeter, Karolina, Dumontet, Charles, Raźny, Malgorzata, Moreno, Victor, Buda, Gabriele, Beider, Katia, Varkonyi, Judit, Avet-Loiseau, Hervé, Martinez-Lopez, Joaquín, Marques, Herlander, Watek, Marzena, Sarasquete, Maria Eugenia, Andersen, Vibeke, Karlin, Lionel, Suska, Anna, Kruszewski, Marcin, Abildgaard, Niels, Dudziński, Marek, Butrym, Aleksandra, Nagler, Arnold, Vangsted, Annette Juul, Kadar, Katalin, Waldemar, Tomczak, Jamroziak, Krzysztof, Jacobsen, Svend Erik Hove, Ebbesen, Lene Hyldahl, Taszner, Michał, Mazur, Grzegorz, Lesueur, Fabienne, Pelosini, Matteo, Garcia-Sanz, Ramon, Jurczyszyn, Artur, Demangel, Delphine, Reis, Rui Manuel, Iskierka-Jażdżewska, Elżbieta, Markiewicz, Miroslaw, Gemignani, Federica, Subocz, Edyta, Zawirska, Daria, Druzd-Sitek, Agnieszka, Stępień, Anna, Alonso, M. Henar, Sainz, Juan, Canzian, Federico, and Campa, Daniele

Published
2021
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32. P1103: OBINUTUZUMAB INDUCTION AND MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINAEMIA

Author

Wróbel, Tomasz, primary, Kalicinska, Elzbieta, additional, Maciej Zaucha, Jan, additional, Morawska, Marta, additional, Giannopoulos, Krzysztof, additional, Jamroziak, Krzysztof, additional, Lech-Marańda, Ewa, additional, Taszner, Michał, additional, Szeremet, Agnieszka, additional, Małcecki, Bartosz, additional, Łojko-Dankowska, Anna, additional, and Dytfeld, Dominik, additional

Published
2023
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34. Organizing pneumonia associated with Richter transformation in chronic lymphocytic leukemia: a case report and review of the literature.

Author

GRYCUK, WIKTORIA, LANGFORT, RENATA, RYMKIEWICZ, GRZEGORZ, GRABOWSKA-DERLATKA, LARETTA, KORCZYŃSKI, PIOTR, JAMROZIAK, KRZYSZTOF, and DROZD-SOKOŁOWSKA, JOANNA

Subjects
PNEUMONIA, CHRONIC lymphocytic leukemia, RICHTER syndrome, PLANT parenchyma, IMMUNOLOGY
Abstract

Organizing pneumonia (OP) is defined histologically by the presence of granulation tissue within alveolar ducts and alveoli. Recently, several lymphoid neoplasms have been implicated as a risk factor for OP, however, OP as a primary manifestation of malignancy transformation has not been widely reported in the literature. Here, we report a case of a patient with a history of chronic lymphocytic leukemia (CLL) who presented with weight loss, low-grade fever, lymphadenopathy, and bilateral pulmonary infiltrates revealed in imaging studies. Video-assisted thoracoscopic lung biopsy showed CLL cells within the pulmonary vessels and areas of OP in the lung parenchyma. Subsequent lymph nodes biopsies were consistent with CLL transformation to diffuse large B-cell lymphoma (DLBCL). To our knowledge, this is the first reported case of OP associated with CLL transformation into DLBCL. This case suggests that OP could represent a form of immunological reaction to ongoing Richter transformation. [ABSTRACT FROM AUTHOR]

Published
2024
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38. The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients with Multiple Myeloma over 75 Years of Age

Author

Tyczyńska, Agata, primary, Krzempek, Marcela Krzysława, additional, Cortez, Alexander Jorge, additional, Jurczyszyn, Artur, additional, Godlewska, Katarzyna, additional, Ciepłuch, Hanna, additional, Subocz, Edyta, additional, Hałka, Janusz, additional, Kulikowska de Nałęcz, Anna, additional, Wiśniewska, Anna, additional, Świderska, Alina, additional, Waszczuk-Gajda, Anna, additional, Drozd-Sokołowska, Joanna, additional, Guzicka-Kazimierczak, Renata, additional, Wiśniewski, Kamil, additional, Porowska, Agnieszka, additional, Knopińska-Posłuszny, Wanda, additional, Kłoczko, Janusz, additional, Rzepecki, Piotr, additional, Woszczyk, Dariusz, additional, Symonowicz, Hanna, additional, Basak, Grzegorz Władysław, additional, Zdziarska, Barbara, additional, Jamroziak, Krzysztof, additional, and Zaucha, Jan M., additional

Published
2023
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40. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization

Author

Clavero, Esther, primary, Sanchez-Maldonado, José Manuel, additional, Macauda, Angelica, additional, Ter Horst, Rob, additional, Sampaio-Marques, Belém, additional, Jurczyszyn, Artur, additional, Clay-Gilmour, Alyssa, additional, Stein, Angelika, additional, Hildebrandt, Michelle A. T., additional, Weinhold, Niels, additional, Buda, Gabriele, additional, García-Sanz, Ramón, additional, Tomczak, Waldemar, additional, Vogel, Ulla, additional, Jerez, Andrés, additional, Zawirska, Daria, additional, Wątek, Marzena, additional, Hofmann, Jonathan N., additional, Landi, Stefano, additional, Spinelli, John J., additional, Butrym, Aleksandra, additional, Kumar, Abhishek, additional, Martínez-López, Joaquín, additional, Galimberti, Sara, additional, Sarasquete, María Eugenia, additional, Subocz, Edyta, additional, Iskierka-Jażdżewska, Elzbieta, additional, Giles, Graham G., additional, Rybicka-Ramos, Malwina, additional, Kruszewski, Marcin, additional, Abildgaard, Niels, additional, Verdejo, Francisco García, additional, Sánchez Rovira, Pedro, additional, da Silva Filho, Miguel Inacio, additional, Kadar, Katalin, additional, Razny, Małgorzata, additional, Cozen, Wendy, additional, Pelosini, Matteo, additional, Jurado, Manuel, additional, Bhatti, Parveen, additional, Dudzinski, Marek, additional, Druzd-Sitek, Agnieszka, additional, Orciuolo, Enrico, additional, Li, Yang, additional, Norman, Aaron D., additional, Zaucha, Jan Maciej, additional, Reis, Rui Manuel, additional, Markiewicz, Miroslaw, additional, Rodríguez Sevilla, Juan José, additional, Andersen, Vibeke, additional, Jamroziak, Krzysztof, additional, Hemminki, Kari, additional, Berndt, Sonja I., additional, Rajkumar, Vicent, additional, Mazur, Grzegorz, additional, Kumar, Shaji K., additional, Ludovico, Paula, additional, Nagler, Arnon, additional, Chanock, Stephen J., additional, Dumontet, Charles, additional, Machiela, Mitchell J., additional, Varkonyi, Judit, additional, Camp, Nicola J., additional, Ziv, Elad, additional, Vangsted, Annette Juul, additional, Brown, Elizabeth E., additional, Campa, Daniele, additional, Vachon, Celine M., additional, Netea, Mihai G., additional, Canzian, Federico, additional, Försti, Asta, additional, and Sainz, Juan, additional

Published
2023
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42. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma:A Meta-Analysis of Three Large Cohorts and Functional Characterization

Author

Clavero, Esther, Sanchez-Maldonado, José Manuel, Macauda, Angelica, Ter Horst, Rob, Sampaio-Marques, Belém, Jurczyszyn, Artur, Clay-Gilmour, Alyssa, Stein, Angelika, Hildebrandt, Michelle A.T., Weinhold, Niels, Buda, Gabriele, García-Sanz, Ramón, Tomczak, Waldemar, Vogel, Ulla, Jerez, Andrés, Zawirska, Daria, Wątek, Marzena, Hofmann, Jonathan N., Landi, Stefano, Spinelli, John J., Butrym, Aleksandra, Kumar, Abhishek, Martínez-López, Joaquín, Galimberti, Sara, Sarasquete, María Eugenia, Subocz, Edyta, Iskierka-Jażdżewska, Elzbieta, Giles, Graham G., Rybicka-Ramos, Malwina, Kruszewski, Marcin, Abildgaard, Niels, Verdejo, Francisco García, Sánchez Rovira, Pedro, da Silva Filho, Miguel Inacio, Kadar, Katalin, Razny, Małgorzata, Cozen, Wendy, Pelosini, Matteo, Jurado, Manuel, Bhatti, Parveen, Dudzinski, Marek, Druzd-Sitek, Agnieszka, Orciuolo, Enrico, Li, Yang, Norman, Aaron D., Zaucha, Jan Maciej, Reis, Rui Manuel, Markiewicz, Miroslaw, Rodríguez Sevilla, Juan José, Andersen, Vibeke, Jamroziak, Krzysztof, Hemminki, Kari, Berndt, Sonja I., Rajkumar, Vicent, Mazur, Grzegorz, Kumar, Shaji K., Ludovico, Paula, Nagler, Arnon, Chanock, Stephen J., Dumontet, Charles, Machiela, Mitchell J., Varkonyi, Judit, Camp, Nicola J., Ziv, Elad, Vangsted, Annette Juul, Brown, Elizabeth E., Campa, Daniele, Vachon, Celine M., Netea, Mihai G., Canzian, Federico, Försti, Asta, Sainz, Juan, Clavero, Esther, Sanchez-Maldonado, José Manuel, Macauda, Angelica, Ter Horst, Rob, Sampaio-Marques, Belém, Jurczyszyn, Artur, Clay-Gilmour, Alyssa, Stein, Angelika, Hildebrandt, Michelle A.T., Weinhold, Niels, Buda, Gabriele, García-Sanz, Ramón, Tomczak, Waldemar, Vogel, Ulla, Jerez, Andrés, Zawirska, Daria, Wątek, Marzena, Hofmann, Jonathan N., Landi, Stefano, Spinelli, John J., Butrym, Aleksandra, Kumar, Abhishek, Martínez-López, Joaquín, Galimberti, Sara, Sarasquete, María Eugenia, Subocz, Edyta, Iskierka-Jażdżewska, Elzbieta, Giles, Graham G., Rybicka-Ramos, Malwina, Kruszewski, Marcin, Abildgaard, Niels, Verdejo, Francisco García, Sánchez Rovira, Pedro, da Silva Filho, Miguel Inacio, Kadar, Katalin, Razny, Małgorzata, Cozen, Wendy, Pelosini, Matteo, Jurado, Manuel, Bhatti, Parveen, Dudzinski, Marek, Druzd-Sitek, Agnieszka, Orciuolo, Enrico, Li, Yang, Norman, Aaron D., Zaucha, Jan Maciej, Reis, Rui Manuel, Markiewicz, Miroslaw, Rodríguez Sevilla, Juan José, Andersen, Vibeke, Jamroziak, Krzysztof, Hemminki, Kari, Berndt, Sonja I., Rajkumar, Vicent, Mazur, Grzegorz, Kumar, Shaji K., Ludovico, Paula, Nagler, Arnon, Chanock, Stephen J., Dumontet, Charles, Machiela, Mitchell J., Varkonyi, Judit, Camp, Nicola J., Ziv, Elad, Vangsted, Annette Juul, Brown, Elizabeth E., Campa, Daniele, Vachon, Celine M., Netea, Mihai G., Canzian, Federico, Försti, Asta, and Sainz, Juan

Abstract

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4)

Published
2023

43. The PANcreatic Disease ReseArch (PANDoRA) consortium:Ten years’ experience of association studies to understand the genetic architecture of pancreatic cancer

Author

Campa, Daniele, Gentiluomo, Manuel, Stein, Angelika, Aoki, Mateus Nóbrega, Oliverius, Martin, Vodičková, Ludmila, Jamroziak, Krzysztof, Theodoropoulos, George, Pasquali, Claudio, Greenhalf, William, Arcidiacono, Paolo Giorgio, Uzunoglu, Faik, Pezzilli, Raffaele, Luchini, Claudio, Puzzono, Marta, Loos, Martin, Giaccherini, Matteo, Katzke, Verena, Mambrini, Andrea, Kiudeliene, Edita, Federico, Kauffmann Emanuele, Johansen, Julia, Hussein, Tamás, Mohelnikova-Duchonova, Beatrice, van Eijck, Casper H.J., Brenner, Hermann, Farinella, Riccardo, Pérez, Juan Sainz, Lovecek, Martin, Büchler, Markus W., Hlavac, Viktor, Izbicki, Jakob R., Hackert, Thilo, Chammas, Roger, Zerbi, Alessandro, Lawlor, Rita, Felici, Alessio, Götz, Mara, Capurso, Gabriele, Ginocchi, Laura, Gazouli, Maria, Kupcinskas, Juozas, Cavestro, Giulia Martina, Vodicka, Pavel, Moz, Stefania, Neoptolemos, John P., Kunovsky, Lumir, Bojesen, Stig E., Carrara, Silvia, Gioffreda, Domenica, Morkunas, Egidijus, Abian, Olga, Bunduc, Stefania, Basso, Daniela, Boggi, Ugo, Wlodarczyk, Barbara, Szentesi, Andrea, Vanella, Giuseppe, Chen, Inna, Bijlsma, Maarten F., Kiudelis, Vytautas, Landi, Stefano, Schöttker, Ben, Corradi, Chiara, Giese, Nathalia, Kaaks, Rudolf, Peduzzi, Giulia, Hegyi, Péter, Morelli, Luca, Furbetta, Niccolò, Soucek, Pavel, Latiano, Anna, Talar-Wojnarowska, Renata, Lindgaard, Sidsel C., Dijk, Frederike, Milanetto, Anna Caterina, Tavano, Francesca, Cervena, Klara, Erőss, Bálint, Testoni, Sabrina G., Verhagen-Oldenampsen, Judith H.E., Małecka-Wojciesko, Ewa, Costello, Eithne, Salvia, Roberto, Maiello, Evaristo, Ermini, Stefano, Sperti, Cosimo, Holleczek, Bernd, Perri, Francesco, Skieceviciene, Jurgita, Archibugi, Livia, Lucchesi, Maurizio, Rizzato, Cosmeri, Canzian, Federico, Campa, Daniele, Gentiluomo, Manuel, Stein, Angelika, Aoki, Mateus Nóbrega, Oliverius, Martin, Vodičková, Ludmila, Jamroziak, Krzysztof, Theodoropoulos, George, Pasquali, Claudio, Greenhalf, William, Arcidiacono, Paolo Giorgio, Uzunoglu, Faik, Pezzilli, Raffaele, Luchini, Claudio, Puzzono, Marta, Loos, Martin, Giaccherini, Matteo, Katzke, Verena, Mambrini, Andrea, Kiudeliene, Edita, Federico, Kauffmann Emanuele, Johansen, Julia, Hussein, Tamás, Mohelnikova-Duchonova, Beatrice, van Eijck, Casper H.J., Brenner, Hermann, Farinella, Riccardo, Pérez, Juan Sainz, Lovecek, Martin, Büchler, Markus W., Hlavac, Viktor, Izbicki, Jakob R., Hackert, Thilo, Chammas, Roger, Zerbi, Alessandro, Lawlor, Rita, Felici, Alessio, Götz, Mara, Capurso, Gabriele, Ginocchi, Laura, Gazouli, Maria, Kupcinskas, Juozas, Cavestro, Giulia Martina, Vodicka, Pavel, Moz, Stefania, Neoptolemos, John P., Kunovsky, Lumir, Bojesen, Stig E., Carrara, Silvia, Gioffreda, Domenica, Morkunas, Egidijus, Abian, Olga, Bunduc, Stefania, Basso, Daniela, Boggi, Ugo, Wlodarczyk, Barbara, Szentesi, Andrea, Vanella, Giuseppe, Chen, Inna, Bijlsma, Maarten F., Kiudelis, Vytautas, Landi, Stefano, Schöttker, Ben, Corradi, Chiara, Giese, Nathalia, Kaaks, Rudolf, Peduzzi, Giulia, Hegyi, Péter, Morelli, Luca, Furbetta, Niccolò, Soucek, Pavel, Latiano, Anna, Talar-Wojnarowska, Renata, Lindgaard, Sidsel C., Dijk, Frederike, Milanetto, Anna Caterina, Tavano, Francesca, Cervena, Klara, Erőss, Bálint, Testoni, Sabrina G., Verhagen-Oldenampsen, Judith H.E., Małecka-Wojciesko, Ewa, Costello, Eithne, Salvia, Roberto, Maiello, Evaristo, Ermini, Stefano, Sperti, Cosimo, Holleczek, Bernd, Perri, Francesco, Skieceviciene, Jurgita, Archibugi, Livia, Lucchesi, Maurizio, Rizzato, Cosmeri, and Canzian, Federico

Abstract

Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies., Pancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.

Published
2023

44. A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk

Author

Dicanio, Marco, Giaccherini, Matteo, Clay-Gilmour, Alyssa, Macauda, Angelica, Sainz, Juan, Machiela, Mitchell J., Rybicka-Ramos, Malwina, Norman, Aaron D., Tyczyńska, Agata, Chanock, Stephen J., Barington, Torben, Kumar, Shaji K., Bhatti, Parveen, Cozen, Wendy, Brown, Elizabeth E., Suska, Anna, Haastrup, Eva K., Orlowski, Robert Z., Dudziński, Marek, Garcia-Sanz, Ramon, Kruszewski, Marcin, Martinez-Lopez, Joaquin, Beider, Katia, Iskierka-Jazdzewska, Elżbieta, Pelosini, Matteo, Berndt, Sonja I., Raźny, Małgorzata, Jamroziak, Krzysztof, Rajkumar, S. Vincent, Jurczyszyn, Artur, Vangsted, Annette Juul, Collado, Pilar Garrido, Vogel, Ulla, Hofmann, Jonathan N., Petrini, Mario, Butrym, Aleksandra, Slager, Susan L., Ziv, Elad, Subocz, Edyta, Giles, Graham G., Andersen, Niels Frost, Mazur, Grzegorz, Watek, Marzena, Lesueur, Fabienne, Hildebrandt, Michelle A.T., Zawirska, Daria, Ebbesen, Lene Hyldahl, Marques, Herlander, Gemignani, Federica, Dumontet, Charles, Várkonyi, Judit, Buda, Gabriele, Nagler, Arnon, Druzd-Sitek, Agnieszka, Wu, Xifeng, Kadar, Katalin, Camp, Nicola J., Grzasko, Norbert, Waller, Rosalie G., Vachon, Celine, Canzian, Federico, Campa, Daniele, Dicanio, Marco, Giaccherini, Matteo, Clay-Gilmour, Alyssa, Macauda, Angelica, Sainz, Juan, Machiela, Mitchell J., Rybicka-Ramos, Malwina, Norman, Aaron D., Tyczyńska, Agata, Chanock, Stephen J., Barington, Torben, Kumar, Shaji K., Bhatti, Parveen, Cozen, Wendy, Brown, Elizabeth E., Suska, Anna, Haastrup, Eva K., Orlowski, Robert Z., Dudziński, Marek, Garcia-Sanz, Ramon, Kruszewski, Marcin, Martinez-Lopez, Joaquin, Beider, Katia, Iskierka-Jazdzewska, Elżbieta, Pelosini, Matteo, Berndt, Sonja I., Raźny, Małgorzata, Jamroziak, Krzysztof, Rajkumar, S. Vincent, Jurczyszyn, Artur, Vangsted, Annette Juul, Collado, Pilar Garrido, Vogel, Ulla, Hofmann, Jonathan N., Petrini, Mario, Butrym, Aleksandra, Slager, Susan L., Ziv, Elad, Subocz, Edyta, Giles, Graham G., Andersen, Niels Frost, Mazur, Grzegorz, Watek, Marzena, Lesueur, Fabienne, Hildebrandt, Michelle A.T., Zawirska, Daria, Ebbesen, Lene Hyldahl, Marques, Herlander, Gemignani, Federica, Dumontet, Charles, Várkonyi, Judit, Buda, Gabriele, Nagler, Arnon, Druzd-Sitek, Agnieszka, Wu, Xifeng, Kadar, Katalin, Camp, Nicola J., Grzasko, Norbert, Waller, Rosalie G., Vachon, Celine, Canzian, Federico, and Campa, Daniele

Abstract

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10−8) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10−7). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus.

Published
2023

45. Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization

Author

European Commission, Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Dietmar Hopp Foundation, Federal Ministry of Education and Research (Germany), Fundação para a Ciência e a Tecnologia (Portugal), Clavero, Esther, Sanchez-Maldonado, José Manuel, Macauda, Angélica, Ter Horst, Rob, Sampaio-Marques, Belém, Jurczyszyn, Artur, Clay-Gilmour, Alyssa, Stein, Angelika, Hildebrandt, Michelle A. T., Weinhold, Niels, Buda, Gabriele, García-Sanz, Ramón, Tomczak, Waldemar, Vogel, Ulla, Jerez, Andrés, Zawirska, Daria, Wątek, Marzena, Hofmann, Jonathan N., Landi, Stefano, Spinelli, John J., Butrym, Aleksandra, Kumar, Abhishek, Martínez-López, Joaquín, Galimberti, Sara, Sarasquete, María Eugenia, Subocz, Edyta, Iskierka-Jażdżewska, Elzbieta, Giles, Graham G., Rybicka-Ramos, Malwina, Kruszewski, Marcin, Abildgaard, Niels, Verdejo, Francisco García, Sánchez Rovira, Pedro, da Silva Filho, Miguel Inacio, Kadar, Katalin, Razny, Małgorzata, Cozen, Wendy, Pelosini, Matteo, Jurado, Manuel, Bhatti, Parveen, Dudzinski, Marek, Druzd-Sitek, Agnieszka, Orciuolo, Enrico, Li, Yang, Norman, Aaron D, Zaucha, Jan Maciej, Reis, Rui Manuel, Markiewicz, Miroslaw, Rodríguez Sevilla, Juan José, Andersen, Vibeke, Jamroziak, Krzysztof, Hemminki, Kari, Berndt, Sonja I., Rajkumar, Vicent, Mazur, Grzegorz, Kumar, Shaji K., Ludovico, Paula, Nagler, Arnon, Chanock, Stephen J., Dumontet, Charles, Machiela, Mitchell J., Varkonyi, Judit, Camp, Nicola J., Ziv, Elad, Vangsted, Annette Juul, Brown, Elizabeth E., Campa, Daniele, Vachon, Celine M., Netea, Mihai G., Canzian, Federico, Försti, Asta, Sainz, Juan, European Commission, Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Dietmar Hopp Foundation, Federal Ministry of Education and Research (Germany), Fundação para a Ciência e a Tecnologia (Portugal), Clavero, Esther, Sanchez-Maldonado, José Manuel, Macauda, Angélica, Ter Horst, Rob, Sampaio-Marques, Belém, Jurczyszyn, Artur, Clay-Gilmour, Alyssa, Stein, Angelika, Hildebrandt, Michelle A. T., Weinhold, Niels, Buda, Gabriele, García-Sanz, Ramón, Tomczak, Waldemar, Vogel, Ulla, Jerez, Andrés, Zawirska, Daria, Wątek, Marzena, Hofmann, Jonathan N., Landi, Stefano, Spinelli, John J., Butrym, Aleksandra, Kumar, Abhishek, Martínez-López, Joaquín, Galimberti, Sara, Sarasquete, María Eugenia, Subocz, Edyta, Iskierka-Jażdżewska, Elzbieta, Giles, Graham G., Rybicka-Ramos, Malwina, Kruszewski, Marcin, Abildgaard, Niels, Verdejo, Francisco García, Sánchez Rovira, Pedro, da Silva Filho, Miguel Inacio, Kadar, Katalin, Razny, Małgorzata, Cozen, Wendy, Pelosini, Matteo, Jurado, Manuel, Bhatti, Parveen, Dudzinski, Marek, Druzd-Sitek, Agnieszka, Orciuolo, Enrico, Li, Yang, Norman, Aaron D, Zaucha, Jan Maciej, Reis, Rui Manuel, Markiewicz, Miroslaw, Rodríguez Sevilla, Juan José, Andersen, Vibeke, Jamroziak, Krzysztof, Hemminki, Kari, Berndt, Sonja I., Rajkumar, Vicent, Mazur, Grzegorz, Kumar, Shaji K., Ludovico, Paula, Nagler, Arnon, Chanock, Stephen J., Dumontet, Charles, Machiela, Mitchell J., Varkonyi, Judit, Camp, Nicola J., Ziv, Elad, Vangsted, Annette Juul, Brown, Elizabeth E., Campa, Daniele, Vachon, Celine M., Netea, Mihai G., Canzian, Federico, Försti, Asta, and Sainz, Juan

Abstract

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influ

Published
2023

46. Identification of novel genetic loci for risk of multiple myeloma by functional annotation

Author

European Commission, National Cancer Institute (US), National Institutes of Health (US), Projekt DEAL, Macauda, Angelica, Briem, Klara, Clay-Gilmour, Alyssa, Cozen, Wendy, Försti, Asta, Giaccherini, Matteo, Corradi, Chiara, Sainz, Juan, Niazi, Yasmeen, Ter Horst, Rob, Li, Yang, Netea, Mihai G., Vogel, Ulla, Hemminki, Kari, Slager, Susan L., Varkonyi, Judit, Andersen, Vibeke, Iskierka-Jazdzewska, Elżbieta, Martínez-López, Joaquín, Zaucha, Jan, Camp, Nicola J., Rajkumar, S. Vincent, Druzd-Sitek, Agnieszka, Bhatti, Parveen, Chanock, Stephen J., Kumar, Shaji K., Subocz, Edyta, Mazur, Grzegorz, Landi, Stefano, Machiela, Mitchell J., Jerez, Andrés, Norman, Aaron D., Hildebrandt, Michelle A. T., Kadar, Katalin, Berndt, Sonja I., Ziv, Elad, Buda, Gabriele, Nagler, Arnon, Dumontet, Charles, Raźny, Malgorzata, Watek, Marzena, Butrym, Aleksandra, Grzasko, Norbert, Dudzinski, Marek, Rybicka-Ramos, Malwina, Matera, Eva-Laure, García-Sanz, Ramón, Goldschmidt, Hartmut, Jamroziak, Krzysztof, Jurczyszyn, Artur, Clavero, Esther, Giles, Graham G., Pelosini, Matteo, Zawirska, Daria, Kruszewski, Marcin, Marques, Herlander, Haastrup, Eva, Sánchez Maldonado, José Manuel, Bertsch, Uta, Rymko, Marcin, Raab, Marc-Steffen, Brown, Elizabeth E., Hofmann, Jonathan N., Vachon, Celine, Campa, Daniele, Canzian, Federico, European Commission, National Cancer Institute (US), National Institutes of Health (US), Projekt DEAL, Macauda, Angelica, Briem, Klara, Clay-Gilmour, Alyssa, Cozen, Wendy, Försti, Asta, Giaccherini, Matteo, Corradi, Chiara, Sainz, Juan, Niazi, Yasmeen, Ter Horst, Rob, Li, Yang, Netea, Mihai G., Vogel, Ulla, Hemminki, Kari, Slager, Susan L., Varkonyi, Judit, Andersen, Vibeke, Iskierka-Jazdzewska, Elżbieta, Martínez-López, Joaquín, Zaucha, Jan, Camp, Nicola J., Rajkumar, S. Vincent, Druzd-Sitek, Agnieszka, Bhatti, Parveen, Chanock, Stephen J., Kumar, Shaji K., Subocz, Edyta, Mazur, Grzegorz, Landi, Stefano, Machiela, Mitchell J., Jerez, Andrés, Norman, Aaron D., Hildebrandt, Michelle A. T., Kadar, Katalin, Berndt, Sonja I., Ziv, Elad, Buda, Gabriele, Nagler, Arnon, Dumontet, Charles, Raźny, Malgorzata, Watek, Marzena, Butrym, Aleksandra, Grzasko, Norbert, Dudzinski, Marek, Rybicka-Ramos, Malwina, Matera, Eva-Laure, García-Sanz, Ramón, Goldschmidt, Hartmut, Jamroziak, Krzysztof, Jurczyszyn, Artur, Clavero, Esther, Giles, Graham G., Pelosini, Matteo, Zawirska, Daria, Kruszewski, Marcin, Marques, Herlander, Haastrup, Eva, Sánchez Maldonado, José Manuel, Bertsch, Uta, Rymko, Marcin, Raab, Marc-Steffen, Brown, Elizabeth E., Hofmann, Jonathan N., Vachon, Celine, Campa, Daniele, and Canzian, Federico

Abstract

Multiple myeloma (MM) is one of the most common hematological malignancies, accounting for 20% of all newly diagnosed hematological cancers [1]. The most recent data from Cancer Today show that in 2020 the number of new MM cases was 176,404 worldwide

Published
2023

47. A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk

Author

Università di Pisa, German Cancer Research Center, Dicanio, Marco, Giaccherini, Matteo, Clay-Gilmour, Alyssa, Macauda, Angelica, Sainz, Juan, Machiela, Mitchell J., Rybicka-Ramos, Malwina, Norman, Aaron D., Tyczyńska, Agata, Chanock, Stephen J., Barington, Torben, Kumar, Shaji K., Bhatti, Parveen, Cozen, Wendy, Brown, Elizabeth E., Suska, Anna, Haastrup, Eva K., Orlowski, R. Z., Dudziński, Marek, García-Sanz, Ramón, Kruszewski, Marcin, Martínez-López, Joaquín, Beider, Katia, Iskierka-Jazdzewska, Elżbieta, Pelosini, Matteo, Berndt, Sonja, Raźny, Małgorzata, Jamroziak, Krzysztof, Rajkumar, S. Vincent, Jurczyszyn, Artur, Vangsted, Annette Juul, Garrido, Pilar, Vogel, Ulla, Hofmann, Jonathan N., Petrini, Mario, Butrym, Aleksandra, Slager, Susan L., Ziv, Elad, Subocz, Edyta, Giles, Graham G., Frost Andersen, Niels, Mazur, Grzegorz, Watek, Marzena, Lesueur, Fabienne, Hildebrandt, Michelle A. T., Zawirska, Daria, Hyldahl Ebbesen, Lene, Marques, Herlander, Gemignani, Federica, Dumontet, Charles, Várkonyi, Judit, Buda, Gabriele, Nagler, Arnon, Druzd-Sitek, Agnieszka, Wu, Xifeng, Kadar, Katalin, Camp, Nicola J., Grzasko, Norbert, Waller, Rosalie G., Vachon, Celine, Canzian, Federico, Campa, Daniele, Università di Pisa, German Cancer Research Center, Dicanio, Marco, Giaccherini, Matteo, Clay-Gilmour, Alyssa, Macauda, Angelica, Sainz, Juan, Machiela, Mitchell J., Rybicka-Ramos, Malwina, Norman, Aaron D., Tyczyńska, Agata, Chanock, Stephen J., Barington, Torben, Kumar, Shaji K., Bhatti, Parveen, Cozen, Wendy, Brown, Elizabeth E., Suska, Anna, Haastrup, Eva K., Orlowski, R. Z., Dudziński, Marek, García-Sanz, Ramón, Kruszewski, Marcin, Martínez-López, Joaquín, Beider, Katia, Iskierka-Jazdzewska, Elżbieta, Pelosini, Matteo, Berndt, Sonja, Raźny, Małgorzata, Jamroziak, Krzysztof, Rajkumar, S. Vincent, Jurczyszyn, Artur, Vangsted, Annette Juul, Garrido, Pilar, Vogel, Ulla, Hofmann, Jonathan N., Petrini, Mario, Butrym, Aleksandra, Slager, Susan L., Ziv, Elad, Subocz, Edyta, Giles, Graham G., Frost Andersen, Niels, Mazur, Grzegorz, Watek, Marzena, Lesueur, Fabienne, Hildebrandt, Michelle A. T., Zawirska, Daria, Hyldahl Ebbesen, Lene, Marques, Herlander, Gemignani, Federica, Dumontet, Charles, Várkonyi, Judit, Buda, Gabriele, Nagler, Arnon, Druzd-Sitek, Agnieszka, Wu, Xifeng, Kadar, Katalin, Camp, Nicola J., Grzasko, Norbert, Waller, Rosalie G., Vachon, Celine, Canzian, Federico, and Campa, Daniele

Abstract

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10−8) with their respective trait. The selected SNPs were analyzed in 2434 MM cases and 3446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1955 MM cases and 1549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147 282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR = 1.22, 95%CI 1.13-1.32, P = 4.81 × 10−7). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus.

Published
2023

48. Genetic and non-genetic risk factors for early-onset pancreatic cancer

Author

Nodari, Ylenia, Gentiluomo, Manuel, Mohelnikova-Duchonova, Beatrice, Kreivenaite, Edita, Milanetto, Anna Caterina, Skieceviciene, Jurgita, Landi, Stefano, Lawlor, Rita T., Petrone, Maria Chiara, Arcidiacono, Paolo Giorgio, Lovecek, Martin, Gazouli, Maria, Bijlsma, Maarten F., Morelli, Luca, Kiudelis, Vytautas, Tacelli, Matteo, Zanette, Dalila Lucíola, Soucek, Pavel, Uzunoglu, Faik, Kaaks, Rudolf, Izbicki, Jakob, Boggi, Ugo, Pezzilli, Raffaele, Mambrini, Andrea, Pasquali, Claudio, van Laarhoven, Hanneke W., Katzke, Verena, Cavestro, Giulia Martina, Sperti, Cosimo, Loos, Martin, Latiano, Anna, Erőss, Bálint, Oliverius, Martin, Johnson, Theron, Basso, Daniela, Neoptolemos, John P., Aoki, Mateus Nóbrega, Greenhalf, William, Vodicka, Pavel, Archibugi, Livia, Vanella, Giuseppe, Lucchesi, Maurizio, Talar-Wojnarowska, Renata, Jamroziak, Krzysztof, Saeedi, Mohammed Al, van Eijck, Casper H.J., Kupcinskas, Juozas, Hussein, Tamás, Puzzono, Marta, Bunduc, Stefania, Götz, Mara, Carrara, Silvia, Szentesi, Andrea, Tavano, Francesca, Moz, Stefania, Hegyi, Péter, Luchini, Claudio, Capurso, Gabriele, Perri, Francesco, Ermini, Stefano, Theodoropoulos, George, Capretti, Giovanni, Palmieri, Orazio, Ginocchi, Laura, Furbetta, Niccolò, Canzian, Federico, Campa, Daniele, Nodari, Ylenia, Gentiluomo, Manuel, Mohelnikova-Duchonova, Beatrice, Kreivenaite, Edita, Milanetto, Anna Caterina, Skieceviciene, Jurgita, Landi, Stefano, Lawlor, Rita T., Petrone, Maria Chiara, Arcidiacono, Paolo Giorgio, Lovecek, Martin, Gazouli, Maria, Bijlsma, Maarten F., Morelli, Luca, Kiudelis, Vytautas, Tacelli, Matteo, Zanette, Dalila Lucíola, Soucek, Pavel, Uzunoglu, Faik, Kaaks, Rudolf, Izbicki, Jakob, Boggi, Ugo, Pezzilli, Raffaele, Mambrini, Andrea, Pasquali, Claudio, van Laarhoven, Hanneke W., Katzke, Verena, Cavestro, Giulia Martina, Sperti, Cosimo, Loos, Martin, Latiano, Anna, Erőss, Bálint, Oliverius, Martin, Johnson, Theron, Basso, Daniela, Neoptolemos, John P., Aoki, Mateus Nóbrega, Greenhalf, William, Vodicka, Pavel, Archibugi, Livia, Vanella, Giuseppe, Lucchesi, Maurizio, Talar-Wojnarowska, Renata, Jamroziak, Krzysztof, Saeedi, Mohammed Al, van Eijck, Casper H.J., Kupcinskas, Juozas, Hussein, Tamás, Puzzono, Marta, Bunduc, Stefania, Götz, Mara, Carrara, Silvia, Szentesi, Andrea, Tavano, Francesca, Moz, Stefania, Hegyi, Péter, Luchini, Claudio, Capurso, Gabriele, Perri, Francesco, Ermini, Stefano, Theodoropoulos, George, Capretti, Giovanni, Palmieri, Orazio, Ginocchi, Laura, Furbetta, Niccolò, Canzian, Federico, and Campa, Daniele

Abstract

Background: Early-onset pancreatic cancer (EOPC) represents 5–10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC. Methods: A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed. Results: Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69–5.04, P = 1.44 × 10−4). For diabetes, the corresponding OR was 14.95 (95% CI 3.41–65.50, P = 3.58 × 10−4). Conclusion: In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC.

Published
2023

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