tbuckley/cabot-search huggingface dataset:
Abstract 3534: The study of Lynch syndrome in a special population reveals a strong founder effect and an unusual mutational mechanism in familial adenomatous polyposis
Authors: Abdul K. Siraj, Sandeep K. Parvathareddy, Rong Bu, Tariq Masoodi, Khadija Alobaisi, Maha Alrasheed, Saeeda O. Ahmed, Zeeshan Qadri, Padmanaban Annaiyappanaidu, Allianah Benito, Dionne R. Rala, Fowzan Al-Kuraya, Khawla S. Al-Kuraya
Journal: Cancer Research (2020)

Abstract Lynch syndrome (LS) is the leading cause of hereditary colorectal cancer (CRC). Germline mutations in DNA mismatch-repair (MMR) genes (MLH1, PMS2, MSH2, and MSH6) are known to cause LS in the heterozygous state. Biallelic mutations in these genes cause mismatch repair cancer syndrome (MMRCS), a very rare childhood cancer syndrome that predisposes to CRC among other cancer types. In this study, we aimed to characterize the mutational landscape of LS in a large CRC cohort (n=1,207) from a population with high rates of consanguinity. The overall contribution of germline mutations in LS gene was comparable to that observed in outbred populations (26/1207). Remarkably, however, we also observed the unusual homozygous occurrence of a founder PMS2 mutation. The homozygous individual presented with massive adenomatous polyposis of the colon at age 8 years, and mutation analysis of multiple polyps revealed the occurrence of multiple independent somatic APC mutations. Our study highlights a previously unrecognized role of LS genes in triggering APC-driven tumors, a phenomenon facilitated by consanguinity. Citation Format: Abdul K. Siraj, Sandeep K. Parvathareddy, Rong Bu, Tariq Masoodi, Khadija Alobaisi, Maha Alrasheed, Saeeda O. Ahmed, Zeeshan Qadri, Padmanaban Annaiyappanaidu, Allianah Benito, Dionne R. Rala, Fowzan Al-Kuraya, Khawla S. Al-Kuraya. The study of Lynch syndrome in a special population reveals a strong founder effect and an unusual mutational mechanism in familial adenomatous polyposis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3534.
Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Iacopo Olivotto, Artur Oreziak, Roberto Barriales-Villa, Theodore P Abraham, Ahmad Masri, Pablo Garcia-Pavia, Sara Saberi, Neal K Lakdawala, Matthew T Wheeler, Anjali Owens, Milos Kubanek, Wojciech Wojakowski, Morten K Jensen, Juan Gimeno-Blanes, Kia Afshar, Jonathan Myers, Sheila M Hegde, Scott D Solomon, Amy J Sehnert, David Zhang, Wanying Li, Mondira Bhattacharya, Jay M Edelberg, Cynthia Burstein Waldman, Steven J Lester, Andrew Wang, Carolyn Y Ho, Daniel Jacoby, Jozef Bartunek, Antoine Bondue, Emeline Van Craenenbroeck, Milos Kubanek, David Zemanek, Morten Jensen, Jens Mogensen, Jens Jakob Thune, Philippe Charron, Albert Hagege, Olivier Lairez, Jean-Noël Trochu, Christoph Axthelm, Hans-Dirk Duengen, Norbert Frey, Veselin Mitrovic, Michael Preusch, Jeanette Schulz-Menger, Tim Seidler, Michael Arad, Majdi Halabi, Amos Katz, Daniel Monakier, Offir Paz, Samuel Viskin, Donna Zwas, Iacopo Olivotto, Hans Peter Brunner-La Rocca, Michelle Michels, Dariusz Dudek, Zofia Oko-Sarnowska, Artur Oreziak, Wojciech Wojakowski, Nuno Cardim, Helder Pereira, Roberto Barriales-Villa, Pablo García Pavia, Juan Gimeno Blanes, Rafael Hidalgo Urbano, Luis Miguel Rincón Diaz, Perry Elliott, Zaheer Yousef, Theodore Abraham, Kia Afshar, Paulino Alvarez, Richard Bach, Richard Becker, Lubna Choudhury, David Fermin, Daniel Jacoby, John Jefferies, Christopher Kramer, Neal Lakdawala, Steven Lester, Ali Marian, Ahmad Masri, Mathew Maurer, Sherif Nagueh, Anjali Owens, David Owens, Florian Rader, Sara Saberi, Mark Sherrid, Jamshid Shirani, John Symanski, Aslan Turer, Andrew Wang, Omar Wever-Pinzon, Matthew Wheeler, Timothy Wong, Mohamad Yamani
Journal: The Lancet (2020)
Abstract 5826: Molecular mechanism of OLIG2-CDK2 interaction in glioma cells
Authors: Norihiko Saito, Nozomi Hirai, Sho Sato, Yu Hiramoto, Satoshi Fujita, Haruo Nakayama, Morito Hayashi, Takatoshi Sakurai, Satoshi Iwabuchi
Journal: Cancer Research (2020)

Abstract Oligodendrocyte transcription factor 2 (Olig2) promotes proliferation of normal neural stem/progenitor cells and glioma cells. However, the mechanisms underlying the regulation of Olig2 remain largely unknown. Here we identified Olig2 as a critical phosphorylation target for cyclin-dependent kinase 2 (CDK2). CDK2-mediated Olig2 phosphorylation stabilizes Olig2 protein from proteasomal degradation. Phosphorylated Olig2 binds to the E-Box regions of p27 promoter and represses p27 transcription, which in turn activates CDK2 in positive feedback manner. CDK2-mediated Olig2 phosphorylation promotes cell cycle progression, cell proliferation, and tumorigenesis. Olig2 inhibition disrupted cell cycle control mechanism by decreasing CDK2 and elevating apoptosis-related molecules. Inhibition of CDK2 activity disrupted Olig2-CDK2 interactions and attenuated Olig2 protein stability. In addition, Olig2-high glioma initiating cells are highly sensitive to CDK2 inhibitor treatment, indicating that Olig2 can be a biomarker for personalized treatment for glioblastoma patients with CDK2 inhibitors. Further investigation on these mechanisms may lead to novel targeted therapy on GBMs with high Olig2 expression. Citation Format: Norihiko Saito, Nozomi Hirai, Sho Sato, Yu Hiramoto, Satoshi Fujita, Haruo Nakayama, Morito Hayashi, Takatoshi Sakurai, Satoshi Iwabuchi. Molecular mechanism of OLIG2-CDK2 interaction in glioma cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5826.
Piperacillin/tazobactam selects an ampC derepressed E. cloacae complex mutant in a diabetic osteoarticular infection
Authors: Milo Moraz, Claire Bertelli, Guy Prod'hom, Antony Croxatto, Gilbert Greub, Sami Abou-Khalil, Oliver Borens, Sylvain Meylan
Journal: Clinical Microbiology and Infection (2020)
HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients
Authors: Lena Berchtold, Eric Letouzé, Mariam Priya Alexander, Guillaume Canaud, Anne-Els van de Logt, Patrick Hamilton, Christiane Mousson, Vincent Vuiblet, Ann M. Moyer, Sylvain Guibert, Petra Mrázová, Charlène Levi, Valérie Dubois, Josep Maria Cruzado, Armando Torres, Manish J. Gandhi, Nadhir Yousfi, Vladimir Tesar, Ondřej Viklický, Maryvonne Hourmant, Bruno Moulin, Philippe Rieu, Gabriel Choukroun, Christophe Legendre, Jack Wetzels, Paul Brenchley, José Aurelio Ballarín Castan, Hanna Debiec, Pierre Ronco
Journal: Kidney International (2020)
Abstract 2589: Dysregulation of RalGAPA2 in hepatocellular carcinoma
Authors: Lu Tian, Lo Kong Chan, Daniel Wai Hung HO, LuQing Zhao, Irene Oi Lin NG
Journal: Cancer Research (2020)

Abstract RalGTPases are Ras-like G-proteins which cycle between the active GTP-bound and the inactive GDP-bound forms. Elevation of expression and activity of RalGTPase has been demonstrated to play an oncogenic role in human cancers. RalA activity could be positively regulated by RalGEF and negatively regulated by RalGAP. The functional RalGAP complex consists of either one of the catalytic subunits, RalGAPA1 or RalGAPA2, together with the regulatory subunit, RalGAPB. In this study, we aimed to investigate the potential role of RalGAPA2 dysregulation and its functional significance in hepatocellular carcinoma (HCC). By RNA-sequencing analysis in human HCC tissues and cell lines, we found that RalGAPA2 was the predominantly expressed RalGAP catalytic subunit in the liver. To examine the RalGAPA2 expression in HCC, we performed qPCR analysis in paired HCC tissues (n=90), and 37.8% of the HCC samples showed a 2-fold downregulation of RalGAPA2. Clinically, downregulation of RalGAPA2 was significantly correlated with a lower cellular differentiation (P=0.034) and a shorter overall survival rate (P=0.045). Interestingly, HCC tumors showing combined upregulation of RalA and downregulation of RalGAPA2 tended to be associated with more aggressive tumor behaviour, including higher occurrence of venous invasion (P=0.001) and more advanced TNM stage (P=0.007). On the other hand, by targeted-DNA sequencing, RalGAPA2 was identified to be recurrently mutated in 7.4% of the patients in a HBV-associated HCC cohort (n=95). Functionally, CRISPR/Cas9-mediated RalGAPA2 knockout HCC cells showed an enhanced migratory ability when compared to the control cells, underlying an upregulation of RalA activity. In HCC, expression of RalA isoform was found to be specifically upregulated and functionally supporting HCC metastasis. Also, inhibition of RalGAP has been demonstrated to promote RalA activity and enhance cell invasion in several cancer types, including oral squamous cell carcinoma, prostate and bladder cancer. Consistently, the inverse correlation between the RalA activity and RalGAPA2 expression was also observed in a panel of HCC cell lines. Furthermore, HCC cells possessing a higher RalA activity were demonstrated to be more prone to RBC8 treatment, a RalGTPase-specific inhibitor. Taken together, our results suggested that RalGAPA2 might play a potential tumor suppressive role in HCC by negatively regulating RalA activity. Citation Format: Lu Tian, Lo Kong Chan, Daniel Wai Hung HO, LuQing Zhao, Irene Oi Lin NG. Dysregulation of RalGAPA2 in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2589.
The Aged Microenvironment of Melanoma Feeds Escape from Targeted Therapy
Authors: Emily D. Montal, Richard M. White
Journal: Cancer Discovery (2020)

Alicea and colleagues demonstrate that aged fibroblasts secrete lipids into the tumor microenvironment, allowing for nutrient exchange with melanoma cells. This supportive function of fibroblasts results in increased resistance to BRAF/MEKi therapy in the context of an aged microenvironment, providing crucial mechanistic insight into age-related drug resistance.See related article by Alicea et al., p. 1282.
Abstract 3426: A synthetic lethality approach to eradicate AML via synergistic activation of pro-apoptotic p53 by MDM2 and BET inhibitors
Authors: Sha Li, Anne Latif, Ashley Newcombe, Kathryn Gilroy, Neil Robertson, Xue Lei, Darren Finlay, Helen Stewart, Karina Barbosa, Brian Higgins, Tim Chevassut, Xu Huang, Mhairi Copland, Karen Keeshan, Ani Deshpande, Peter Adams
Journal: Cancer Research (2020)

Abstract Acute Myeloid Leukemia (AML) is a typically-lethal molecularly heterogeneous disease, with few broad-spectrum therapeutic targets. Unusually, over 90% of AML patients retain wild type TP53, encoding pro-apoptotic tumor suppressor p53. However, wild-type p53 functions are frequently suppressed by MDM2, an E3 ubiquitin ligase that targets p53 for proteasomal degradation. MDM2 inhibitors (MDM2i), which activate wild-type p53, show encouraging pre-clinical activity, but limited clinical activity. In an effort to find targets that synergize with p53 activation and minimize toxicity via MDM2i, we performed a cell-based synthetic lethal drug screen and a CRISPR viability screen. By integrating the results of these two screens, we found inhibition of BRD4 activates p53 and its target genes. BRD4 (Bromodomain-containing protein 4) is a member of the bromodomain and extraterminal (BET) family proteins, which has typically been reported to activate genes, such as c-MYC, BCL2 and CDK4/6. However, we unexpectedly reveal that BRD4 acts as a transcriptional repressor of p53 target genes. Our combined therapy of MDM2i and BETi is synergistically lethal to human AML cell lines harboring wild type p53 in vitro, against two mouse models of AML in vivo, and against several primary human patient blasts in vitro. Synergistic cell killing was associated with synergistic activation of p53 target genes, and cell killing and p53 target gene expression. Taken together, our data show BRD4 represses p53-mediated transcription activation and apoptosis in AML. Therefore, targetable wild-type p53 and a transcriptional repressor function of BRD4 together represent a potential broad-spectrum synthetic therapeutic vulnerability for AML. Citation Format: Sha Li, Anne Latif, Ashley Newcombe, Kathryn Gilroy, Neil Robertson, Xue Lei, Darren Finlay, Helen Stewart, Karina Barbosa, Brian Higgins, Tim Chevassut, Xu Huang, Mhairi Copland, Karen Keeshan, Ani Deshpande, Peter Adams. A synthetic lethality approach to eradicate AML via synergistic activation of pro-apoptotic p53 by MDM2 and BET inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3426.
Abstract 5442: The Collaborative Ocular Oncology Group study number 2: A prospective multi-center evaluation of uveal melanoma prognostic biomarkers
Authors: Christina L. Decatur, Michael A. Durante, Zelia M. Correa, Thomas M. Aaberg, Prithvi Mruthyunjaya, Amy C. Schefler, J. William Harbour
Journal: Cancer Research (2020)

Abstract Introduction: Uveal melanoma (UM) is a highly aggressive eye cancer that leads to metastatic death in up to half of patients. UM has a propensity to undergo early micrometastasis prior to treatment of the primary tumor, with later emergence of overt metastatic disease. UM can be stratified into Class 1 (low metastatic risk) and Class 2 (high metastatic risk) using a prospectively validated 12-gene expression profile (GEP) molecular prognostication classifier. The Collaborative Ocular Oncology Group Study 2 (COOG2) is being conducted to prospectively evaluate new prognostic biomarkers in UM, including expression of PRAME, and prognostic driver mutations in BAP1, SF3B1, and EIF1AX. Methods: The COOG2 is a 24 center, prospective study of UM patients undergoing prognostic testing using the CLIA-certified DecisionDx-UM test (Castle Biosciences, Inc) between July 2017 and December 2019. Molecular analysis is performed on residual clinical samples. Data collected include clinical annotations, patient outcomes, GEP, PRAME status, and mutations in BAP1, SF3B1, and EIF1AX. Results: To date, there are 1300 participants enrolled. The baseline characteristics are as follows: 52% male, and 48% female; 87% non-Hispanic, 3% Hispanic, and 10% unknown. GEP classification is 66% class 1 and 34% class 2. PRAME status is 68% PRAME (-) and 32% PRAME (+). Targeted sequencing has been performed on 650 samples and is being analyzed. Conclusions: The COOG2 will establish a new standard of prognostic testing accuracy from a single fine needle biopsy in UM. The resulting integrated prognostic testing platform will be used as a stratification tool for entry into clinical trials of adjuvant therapy in high-risk patients. Citation Format: Christina L. Decatur, Michael A. Durante, Zelia M. Correa, Thomas M. Aaberg, Prithvi Mruthyunjaya, Amy C. Schefler, J. William Harbour. The Collaborative Ocular Oncology Group study number 2: A prospective multi-center evaluation of uveal melanoma prognostic biomarkers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5442.
Characteristics of exceptional responders to autologous stem cell transplantation in multiple myeloma
Authors: Ashley Paquin, Alissa Visram, Shaji K. Kumar, Morie A. Gertz, Hafsa Cantwell, Francis K. Buadi, Martha Q. Lacy, Angela Dispenzieri, David Dingli, Lisa Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronald S. Go, Yi Lin, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar
Journal: Blood Cancer Journal (2020)

Abstract Autologous stem cell transplantation (ASCT) is an important treatment modality in multiple myeloma (MM). However, relapse following ASCT is considered almost inevitable. This study aimed to characterize exceptional responders to ASCT, defined as progression-free survival (PFS) &gt;8 years in the absence of maintenance therapy. We retrospectively analyzed patients treated at Mayo Clinic between August 1, 1998 and January 3, 2006, and included those with symptomatic MM, treated with an ASCT within 12 months of diagnosis. We found that 46 (9%) of the 509 patients who underwent ASCT during the study period were exceptional responders. The median duration of follow-up from diagnosis was 16.2 (interquartile range 14.3–17.7) years. The best response to therapy was a complete response (CR) or better in 34 (74%) of patients, and less than a CR in 12 (26%) of patients. The median PFS was 13.8 (95% confidence interval 10.5–18.5) years, and at the time of the last hematology assessment, 24 of 46 (52%) patients remained in remission. In conclusion, we showed that a small subset of patients with MM attains durable disease control without maintenance therapy post ASCT. Pre-emptive identification of these patients may help prevent undue toxicities and costs of subsequent therapy.
Abstract 1374: Preclinical investigation of ATR inhibition alone and in combination with PARP inhibition in high risk neuroblastoma
Authors: Harriet E. Southgate, Lindi Chen, Nicola J. Curtin, Deborah A. Tweddle
Journal: Cancer Research (2020)

Abstract Background:Neuroblastoma (NB) is the commonest extra-cranial malignant solid tumour of childhood and one of the most difficult to cure. DNA damage response (DDR) defects are frequently observed in high risk NB including allelic loss and loss of function mutations in key DDR genes, oncogene induced replication stress (RS) and cell cycle checkpoint dysfunction. Cancer cells with defective cell cycle checkpoint signalling and/or increased oncogene-driven RS are acutely dependent on the DNA damage sensor kinase ATR. This study aims to identify features of NB cell lines leading to ATR inhibitor sensitivity. As PARP inhibition causes RS through unrepaired single strand DNA breaks progressing to replication, we hypothesise that ATR inhibition will increase PARP inhibitor cytotoxicity. Aims: 1) To determine which molecular features lead to sensitivity to VE-821 (ATR inhibitor) in cell lines derived from high-risk NB tumours. 2) To assess synergism between PARP inhibition with olaparib and ATR inhibition in high risk NB cell lines and to measure RS. Materials and Methods: Cell proliferation in response to 72 hours treatment with VE-821 was assessed by XTT assay (Roche) in a panel of 11 NB cell lines and the effect of ATR inhibition on olaparib growth inhibition in 4 cell lines: SHSY5Y, SKNAS, NGP and N20_R1. CHK1S345 and H2AXS129 phosphorylation was assessed using Western blotting to determine ATR activity and RS respectively. RS was also measured by γH2AX foci formation using immunofluorescent microscopy. Results: VE-821 caused significantly more growth inhibition in MYCN amplified cell lines and cell lines with low ATM protein expression by XTT assay (p&amp;lt;0.05 Mann-Whitney U test). Olaparib (5 µM) treatment increased CHK1S345 and H2AXS129 phosphorylation after 24 hours treatment in all cell lines. H2AXS129 phosphorylation and foci number was further increased with the addition of VE-821 (1 µM). ATR inhibition prevented CHK1S345 phosphorylation. In cell proliferation assays, combination index analysis (Calcusyn) showed that ATR inhibition by VE-821 is synergistic with olaparib at sub lethal concentrations (&amp;lt;1 µM) (CI value 0.04-0.89). Conclusion: MCYN amplification and low ATM protein expression are determinants of ATRi sensitivity in NB cell lines. ATR inhibition by VE-821 is synergistic with olaparib at sub lethal concentrations (&amp;lt;1 µM) and further increases the replication stress caused by PARP inhibition. Citation Format: Harriet E. Southgate, Lindi Chen, Nicola J. Curtin, Deborah A. Tweddle. Preclinical investigation of ATR inhibition alone and in combination with PARP inhibition in high risk neuroblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1374.
Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms
Authors: Matteo Giaccherini, Angelica Macauda, Nicola Sgherza, Juan Sainz, Federica Gemignani, Josè Manuel Sanchez Maldonado, Manuel Jurado, Francesca Tavano, Grzegorz Mazur, Andrés Jerez, Joanna Góra-Tybor, Aleksandra Gołos, Francisca Hernández Mohedo, Joaquin Martinez Lopez, Judit Várkonyi, Raffaele Spadano, Aleksandra Butrym, Federico Canzian, Daniele Campa
Journal: Blood Cancer Journal (2020)

Abstract Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10 −3 , comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT -rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1- rs9420907-C variant with higher MPN risk (OR allelic = 1.43; 95% CI 1.15–1.77; P = 1.35 × 10 −3 ). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development.
SAT0235 Determinants of productivity costs in as. comparative study in the netherlands, france and belgium
Authors: AH Boonen, D Van der Heijde, H Schouten, R Landewe, F Guillemin, M Dougados, K De Vlam, H Mielants, A Spoorenberg, S Van der Linden
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate determinants of productivity costs in ankylosing spondylitis (AS) in three European countries. <h3>Methods</h3> 216 consecutive prevalent AS out-patients started a 2 year longitudinal cost-of-illness study. AS-related health resource utilisation was collected by questionnaires every 2 months. Productivity costs were calculated by friction cost (FC) method and human capital (HC) approach. Cox proportional hazard analysis with costs as dependent variable was used to assess if ?country? was a determinant of productivity costs after controlling for age, gender, disease duration and time integrated disease activity (BASDAI:0–10; higher values indicating higher disease activity) if FC were the outcome or baseline physical function (BASFI:0–10; higher values indicating worse function) if HC costs were the outcome. <h3>Results</h3> 209 patients completed follow-up. In the Netherlands (NL), (F) and (B) respectively, 70, 69 and 74% of patients were male, mean age 46 (sd:12), 38 (sd: 12) and 42 (sd: 14) yr, mean disease duration 24 (sd:12), 14 (sd:9) and 13 (sd:10) yr and 34, 13 and 24% had manual professions. 196 patients were in working age and 113 patients had a paid job. <h3>Conclusion</h3> In AS, productivity costs determined by FC and HC approach are significantly associated with the country studied. This finding has important consequences for the generalizability of health economic studies.