10 research outputs found
Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.
Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 Ă 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 Ă 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 Ă 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 Ă 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 Ă 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Communityâs Seventh Framework Programme under grant agreement n8 223175
(HEALTH-F2â2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the âCIHR Team in Familial Risks of Breast
Cancerâ program and the Ministry of Economic Development, Innovation and Export Trade of Quebec (PSR-SIIRI-701). Additional support for the iCOGS infrastructure was provided by the
National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112âthe GAME-ON initiative), the Department
of Defence (W81XWH-10-1-0341), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The ABCFS and OFBCR work was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reïŹect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement t by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and M.C.S. is a NHMRC Senior Research Fellow. The OFBCR work was also supported by the Canadian Institutes of Health Research âCIHR Team in Familial Risks of Breast Cancerâ program. The ABCS was funded by the Dutch Cancer Society Grant no. NKI2007-3839 and NKI2009-4363. The ACP study is funded by the Breast Cancer Research Trust, UK. The work of the BBCC was partly funded by ELAN-Programme of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). E.S. is supported by NIHR Comprehensive Biomedical Research Centre, Guyâs & St. Thomasâ NHS Foundation Trust in partnership with Kingâs College London, UK. Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z). I.T. is
supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by the Fondation de France, the French National Institute of Cancer (INCa), The National League against Cancer, the National Agency for Environmental l and Occupational Health and Food Safety (ANSES), the National Agency for Research (ANR), and the Association for Research against Cancer (ARC). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.The CNIO-BCS was supported by the Genome Spain Foundation the Red Temåtica de Investigación Cooperativa en Cåncer and grants from the Asociación Española Contra el Cåncer and the Fondo de Investigación Sanitario PI11/00923 and PI081120). The Human Genotyping-CEGEN Unit, CNIO is supported by the Instituto de Salud Carlos III. D.A. was supported by a Fellowship from the Michael Manzella Foundation (MMF) and was a participant in the CNIO Summer Training Program. The
CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence e data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden WĂŒrttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), as well as the Department of Internal Medicine , Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus Bonn, Germany. The HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation.
The HERPACC was supported by a Grant-in-Aid for ScientiïŹc Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a
Grant-in-Aid for the Third Term Comprehensive 10-Year strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by a research grant from Takeda Science Foundation , by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by National Cancer Center Research and Development Fund. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to N.B), and the Friends of Hannover Medical School (to N.B.). Financial support for KARBAC was provided
through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Stockholm Cancer Foundation and the Swedish Cancer Society. The KBCP was ïŹnancially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish
Cancer Organizations, the Academy of Finland and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation , the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia.
The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704, 454508). Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). G.C.T. and P.W. are supported by the NHMRC. LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018 and 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Instituteâs Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the âStichting tegen Kankerâ (232-2008 and 196-2010). The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I), the Federal Ministry of Education Research (BMBF) Germany (01KH0402), the Hamburg Cancer Society and the German Cancer Research Center (DKFZ). MBCSG is supported by grants from the Italian Association ciation for Cancer Research (AIRC) and by funds from the Italian citizens who allocated a 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects â5 Ă 1000â). The MCBCS was supported by the NIH grants (CA122340, CA128978) and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The MEC was supported by NIH grants CA63464, CA54281, CA098758 and CA132839. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research (grant CRN-87521) and the Ministry of Economic Development, Innovation and Export Trade (grant PSR-SIIRI-701). MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19,tel:08/1/35/19./550), Singapore and the National medical Research
Council, Singapore (NMRC/CG/SERI/2010). The NBCS was supported by grants from the Norwegian Research council (155218/V40, 175240/S10 to A.L.B.D., FUGE-NFR 181600/
V11 to V.N.K. and a Swizz Bridge Award to A.L.B.D.). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen
Shared Resource, which is supported by P30 CA68485. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the
Academy of Finland, the University of Oulu, and the Oulu University Hospital. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NLCP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and
Human Services, USA. pKARMA is a combination of the KARMA and LIBRO-1 studies. KARMA was supported by Mašrit and Hans Rausings Initiative Against Breast Cancer.
KARMA and LIBRO-1 were supported the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linnaeus Centre (Contract ID 70867902) ïŹnanced by the Swedish Research Council. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (AâSTAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation KC was ïŹnanced by the Swedish Cancer Society (5128-B07-01PAF). The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30
CA68485. The SBCS was supported by Yorkshire Cancer Research S305PA, S299 and S295. Funding for the SCCS was provided by NIH grant R01 CA092447. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the
authors and do not necessarily represent the ofïŹcial views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by a programme grant from Cancer Research UK
(C490/A10124) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the National Medical Research Council Start-up Grant and Centre Grant (NMRC/CG/NCIS /2010). The recruitment of controls by the Singapore Consortium of Cohort
Studies-Multi-ethnic cohort (SCCS-MEC) was funded by the Biomedical Research Council (grant number: 05/1/21/19/425).
SKKDKFZS is supported by the DKFZ. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. K. J. is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The TNBCC was supported by the NIH grant (CA128978), the Breast Cancer Research Foundation , Komen Foundation for the Cure, the Ohio State University
Comprehensive Cancer Center, the Stefanie Spielman Fund for Breast Cancer Research and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting
Tsung and Wei Fong Chao Foundation. Part of the TNBCC (DEMOKRITOS) has been co-ïŹnanced by the European Union (European Social Fund â ESF) and Greek National
Funds through the Operational Program âEducation and Life-long Learningâ of the National Strategic Reference Framework (NSRF)âResearch Funding Program of the General Secretariat for Research & Technology: ARISTEIA. The TWBCS is supported by the Institute of Biomedical Sciences, Academia Sinica and the National Science Council, Taiwan. The
UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. Funding to pay the
Open Access publication charges for this article was provided by the Wellcome Trust.This is the advanced access published version distributed under a Creative Commons Attribution License 2.0, which can also be viewed on the publisher's webstie at: http://hmg.oxfordjournals.org/content/early/2014/07/04/hmg.ddu311.full.pdf+htm
Comparison of Prognostic Gene Profiles Using qRT-PCR in Paraffin Samples: A Retrospective Study in Patients with Early Breast Cancer
Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid
Angiogenesis-related gene expression profile with independent prognostic value in advanced ovarian carcinoma.
Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND
Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients.
METHODOLOGY/PRINCIPAL FINDINGS
RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001).
CONCLUSIONS/SIGNIFICANCE
It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.Financial support was given by Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain (FIS07/0651, CM05/00143, and CP05/00248; and Fundación de Investigación Médica Mutua Madrileña.Ye
Common non-synonymous snps associated with breast cancer susceptibility: findings from the breast cancer association consortium
Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 x 10 26], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 x 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 x 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 x 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 x 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act
Angiogenesis-Related Gene Expression Profile with Independent Prognostic Value in Advanced Ovarian Carcinoma
Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression
<p>Mutations affecting the integrity and function of cilia have been identified in various genes over the last decade accounting for a group of diseases called ciliopathies. Ciliopathies display a broad spectrum of phenotypes ranging from mild manifestations to lethal combinations of multiple severe symptoms and most of them share cystic kidneys as a common feature. Our starting point was a consanguineous pedigree with three affected fetuses showing an early embryonic phenotype with enlarged cystic kidneys, liver and pancreas and developmental heart disease. By genome-wide linkage analysis, we mapped the disease locus to chromosome 17q11 and identified a homozygous nonsense mutation in NEK8/NPHP9 that encodes a kinase involved in ciliary dynamics and cell cycle progression. Missense mutations in NEK8/NPHP9 have been identified in juvenile cystic kidney jck mice and in patients suffering from nephronophthisis (NPH), an autosomal-recessive cystic kidney disease. This work confirmed a complete loss of NEK8 expression in the affected fetuses due to nonsense-mediated decay. In cultured fibroblasts derived from these fetuses, the expression of prominent polycystic kidney disease genes (PKD1 and PKD2) was decreased, whereas the oncogene c-MYC was upregulated, providing potential explanations for the observed renal phenotype. We furthermore linked NEK8 with NPHP3, another NPH protein known to cause a very similar phenotype in case of null mutations. Both proteins interact and activate the Hippo effector TAZ. Taken together, our study demonstrates that NEK8 is essential for organ development and that the complete loss of NEK8 perturbs multiple signalling pathways resulting in a severe early embryonic phenotype.</p>
Recommended from our members
7th Drug hypersensitivity meeting: part two
Table of contents Poster walk 11: miscellaneous drug hypersensitivity 2 (P92âP94, P96âP101) P92 16 years of experience with proton pump inhibitors (PPIs) Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco GarcĂa, Antonio Alvarez, Jose Julio Laguna Martinez P93 Allergy evaluation of quinolone induced adverse reactions Jaume MartĂ Garrido, Carla TorĂĄn Barona, Carolina Perales Chorda, RamĂłn LĂłpez Salgueiro, Miguel DĂaz Palacios, Dolores HernĂĄndez FernĂĄndez De Rojas P94 Bupropion-induced acute urticaria and angioedema, a case report Emre Ali Acar, Ayse Aktas, Aylin TĂŒrel Ermertcan, Peyker Temiz P96 Delayed type hypersensitivity and study of cross-reactivity between proton-pump inhibitors Chien-Yio Lin, Chung-Yee Rosaline Hui, Ya-Ching Chang, Chih-Hsun Yang, Wen-Hung Chung P97 Diagnostic work-up in suspected hypersensitivity to proton-pump inhibitors: looking at cross-reactivity FabrĂcia Carolino, Diana Silva, Eunice Dias De Castro, Josefina R. Cernadas P98 Management of infusion-related hypersensitivity reactions to enzyme replacement therapy for lysosomal diseases Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Alex Lacerda, Ana Maria Martins, Ekaterini Goudouris, Marcia Ribeiro, JosĂ© Francisco Da Silva Franco, Leandra Queiroz, Dirceu SolĂ© P99 Management of insulin allergy with continuous subcutaneous insulin infusion Ceyda Tunakan Dalgiç, AytĂŒl Zerrin Sin, Fatma DĂŒsĂŒnĂŒr GĂŒnsen, Gökten Bulut, Fatma ĂmĂŒr Ardeniz, Okan GĂŒlbahar, Emine Nihal Mete Gökmen, Ali Kokuludag P100 Off-label use of icatibant for management of serious angioedema associated with angiotensin inhibitors Ana M. Montoro De Francisco, TalĂa MÂȘ De Vicente JimĂ©nez, Adriana M. Mendoza Parra, Angella M. Burgos Pimentel, Amelia GarcĂa Luque P101 Thiocolchicoside anaphylaxis: an unusual suspect? Luis Amaral, Fabricia Carolino, Leonor Carneiro LeĂŁo, Eunice Castro, Josefina Cernadas Poster walk 12: betalactam hypersensitivity (P102âP111) P102 A curious delayed reading: a case report of a ÎČ-lactam allergy in a child Nicole Pinto, Joana Belo, JoĂŁo Marques, Pedro Carreiro-Martins, Paula Leiria-Pinto P103 Betalactam-induced hypersensitivity: a 10-yearsâ experience Amel Chaabane, Haifa Ben Romdhane, Nadia Ben Fredj, Zohra Chadly, Naceur A. Boughattas, Karim Aouam P104 Cefazolin hypersensitivity: towards optimized diagnosis Astrid P. Uyttebroek, Chris H. Bridts, Antonino Romano, Didier G. Ebo, Vito Sabato P105 Clavulanic acid allergy: two cases report Anabela Lopes, Joana Cosme, Rita Aguiar, Tatiana Lourenço, Maria-JoĂŁo Paes, AmĂ©lia SpĂnola-Santos, Manuel Pereira-Barbosa P106 Diagnosis of betalactam allergy in an allergy department CĂntia Rito Cruz, Rute Pereira Dos Reis, Elza Tomaz, Ana Paula Pires, Filipe InĂĄcio P107 Diagnostic work-up of 410 patients with suspicion of betalactam antibiotic hypersensitivity Filipe Benito-Garcia, InĂȘs Mota, Magna Correia, Ăngela Gaspar, Marta Chambel, Susana Piedade, MĂĄrio Morais-Almeida P108 Immediate selective hypersensitivity reactions to clavulanic acid Alla Nakonechna, Yurij Antipkin, Tetiana Umanets, Fernando Pineda, Francisca Arribas, Volodymyr Lapshyn P109 Prevalence and incidence of penicillin hypersensitivity reactions in Colombia Pablo AndrĂ©s Miranda, Bautista De La Cruz Hoyos P110 Selective sensitization to amoxicilin and clavulanic acid Jose Julio Laguna Martinez, Aranzazu Jimenez Blanco, Javier Dionicio Elera, Cosmin Boteanu, Rosario Gonzalez-Mendiola, Marta Del Pozo P111 Infliximab-specific T cells are detectable also in treated patients who have not developed anti-drug antibodies Alessandra Vultaggio, Francesca Nencini, Sara Pratesi, Andrea Matucci, Enrico Maggi Poster walk 13: biologicals, local anesthetics, others (P112âP118) P112 A case report of allergic immediate systemic reaction to adalimumab and certolizumab Ceyda Tunakan Dalgiç, Fatma DĂŒsĂŒnĂŒr GĂŒnsen, Gökten Bulut, Fatma ĂmĂŒr Ardeniz, Okan GĂŒlbahar, Emine Nihal Mete Gökmen, AytĂŒl Zerrin Sin, Ali Kokuludag P113 Allergy to local anesthetics: negative predictive value of skin tests Ivana Cegec, Danica Juricic Nahal, Viktorija Erdeljic Turk, Matea Radacic Aumiler, Ksenija Makar Ausperger, Iva Kraljickovic, Iveta Simic P114 Cutaneous adverse reactions of molecular targeted agents: a retrospective analysis in 150 patients in our department Yukie Yamaguchi, Tomoya Watanabe, Megumi Satoh, Tomohiko Tanegashima, Kayoko Oda, Hidefumi Wada, Michiko Aihara P115 Generalized paralysis induced by local lidocaine injection Jaechun Jason Lee, Jay Chol Choi, Hwa Young Lee P116 Hypersensitivity to local anaesthetics: a 10 year review Rosa-Anita Rodrigues Fernandes, EmĂlia Faria, Joana Pita, Nuno Sousa, Carmelita Ribeiro, Isabel Carrapatoso, Ana Todo Bom P117 Local anaesthetics: a rare culprit in hypersensitivity reactions Ana Rodolfo, Eunice Dias-Castro, Josefina Cernadas P118 StevensâJohnson syndrome in clinical practice: a variant of clinical course Marina Voronova Poster walk 14: RCM (P119âP128) P119 13 cases of severe anaphylactic reactions due to radiocontrast media Jaume MartĂ Garrido, Ramon Lopez Salgueiro, Diana Kury Valle, VerĂłnica Pacheco Coronel, Carolina Perales ChordĂĄ, Dolores Hernandez Fernandez De Rojas P120 Anaphylactic shock after administration of iodinated contrast medium during cardiac catheterization Roselle Catherine Yu Madamba, Marta Ferrer, Maria Jose Goikoetxea, Carmen DâAmelio, Amalia Bernad, Olga Vega, Gabriel Gastaminza P121 Anaphylactic shock and cardiac arrest induced by gadolinium-based contrast agents Beatriz Pola BibiĂĄn, Marina Lluncor Salazar, Gemma VilĂ Nadal, Ana MarĂa Fiandor Roman, Javier Dominguez Ortega, Miguel Gonzalez Muñoz, Santiago Quirce Gancedo, Maria Rosario Cabañas Moreno P122 Anaphylaxis to gadobenate and cross-reactivity to other gadolinium-based contrast agents in two patients Kathrin Scherer Hofmeier P123 Anaphylaxis to glatiramer acetate in a patient with multiple sclerosis FabrĂcia Carolino, Vladyslava Barzylovych, Josefina R. Cernadas P124 Delayed hypersensitivity reaction to radiocontrast media FabrĂcia Carolino, Diana Silva, Leonor LeĂŁo, Josefina R. Cernadas P125 Drug reaction with eosinophilia and systemic symptoms induced by iodixanol Gemma VilĂ -Nadal, Beatriz Pola, Marina Lluncor, Ana Fiandor, Teresa BellĂłn, Javier DomĂnguez, Santiago Quirce P126 Electronic consultation support system for radiocontrast media hypersensitivity changes clinicianâs behavior Min-Suk Yang, Sun-Sin Kim, Sae-Hoon Kim, Hye-Ryun Kang, Heung-Woo Park, Sang-Heon Cho, Kyung-Up Min, Yoon-Seok Chang P127 Hypersensitivity reactions to iodinated contrast media: skin testing and follow-up Danica Juricic Nahal, Ivana Cegec, Viktorija Erdeljic Turk, Iva Kraljickovic, Matea Radacic Aumiler, Ksenija Makar Ausperger, Iveta Simic P128 Would iodine allergy exist? ClĂ©mence Delahaye, Jenny Flabbee, Julie Waton, Olivia Bauvin, Annick Barbaud Poster walk 15: MPE/type 4 (P129âP137) P129 Delayed hypersensitivity cutaneous reactions: a case/control study from a tunisian database Karim Aouam, Najah Ben Fadhel, Zohra Chadly, Nadia Ben Fredj, Naceur A. Boughattas, Amel Chaabane P130 Delayed hypersensitivity reactions to cephalosporins: a review of seven cases Joana Cosme, Anabela Lopes, AmĂ©lia SpĂnola-Santos, Manuel Pereira-Barbosa P131 Diclofenac induced allergic contact dermatitis: case series of four patients Sandra Jerkovic Gulin, Anca Chiriac P132 Late-onset maculopapular rash to irbesartan BĂĄrbara Kong Cardoso, Elza Tomaz, Regina Viseu, Filipe InĂĄcio P133 Nonimmediate hypersensitivity reactions to betalactams: a retrospective analysis Ana Moreira, Susana Cadinha, Ana Castro Neves, Patricia Barreira, Daniela Malheiro, J. P. Moreira Da Silva P134 Occupational airborne contact dermatitis to omeprazole RuĆŸica Jurakic-Toncic, Suzana Ljubojevic, Petra Turcic P135 Ornidazole-induced fixed drug eruption confirmed by positive patch test on a residual pigmented lesion Liesbeth Gilissen, Sara Huygens, An Goossens P136 Repeated delayed reaction induced by amoxicillin and amoxicillin clavulanate Inmaculada Andreu, Ramon Lopez-Salgueiro, Alicia Martinez Romero, Pau Gomez Cabezas P137 Systemic photosensitivity from fenofibrate in a patient photo-sensitized to ketoprofen Liesbeth Gilissen, An Goossens Poster walk 16: HLA genetics (P138âP146) P138 A copy number variation in ALOX5 and PTGER1 is associated with nonsteroidal anti-inflammatory drugs induced urticaria and/or angioedema Pedro Ayuso Parejo, Maria Del Carmen Plaza-SerĂłn, Inmaculada Doña, Natalia Blanca LĂłpez, Carlos Flores, Luisa Galindo, Ana Molina, James Richard Perkins, Jose Antonio Cornejo-GarcĂa, JosĂ© Augusto GarcĂa-AgĂșndez, Elena GarcĂa-MartĂn, Paloma Campo, MarĂa Gabriela Canto, Miguel Blanca P139 Association of galectin-3 (LGALS3) single nucleotide polymorphisms with non-steroidal anti-inflammatory drugs-induced urticaria/angioedema JosĂ© Antonio Cornejo-Garcia, Inmaculada Doña, Rosa MarĂa GuĂ©ant-RodrĂguez, Natalia Blanca-LĂłpez, MarĂa Carmen Plaza-SerĂłn, Raquel Jurado-Escobar, Esther Barrionuevo, MarĂa Salas, MarĂa Luisa Galindo, Gabriela Canto, Miguel Blanca, Jean-Louis GuĂ©ant P140 Detection of T cell responses to ticlopidine using peripheral blood mononuclear cells from HLA-A*33:03+ healthy donors Toru Usui, Arun Tailor, Lee Faulkner, John Farrell, Ana Alfirevic, B. Kevin Park, Dean J. Naisbitt P141 Epistasis approaches to identify novel genes potentially involved in NSAIDs hypersensitivity James Richard Perkins, Jose Antonio Cornejo GarcĂa, Oswaldo Trelles, Inmaculada Doña, Esther Barrionuevo, MarĂa Salas, MarĂa Auxiliadora Guerrero, Miguel Blanca, Alex Upton P142 Genetic predisposition of cold medicine related SJS/TEN with severe ocular complications Mayumi Ueta, Hiromi Sawai, Chie Sotozono, Katushi Tokunaga, Shigeru Kinoshita P143 HLA-B*13:01 and dapsone induced hypersensitivity in Thai population Chonlaphat Chonlaphat Sukasem, Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Kulprapat Pairayayutakul, Jettanong Klaewsongkram P144 HLA-B*15:02 alleles and lamotrigine-induced cutaneous adverse drug reactions in Thai Chonlaphat Sukasem, N. Koomdee, T. Jantararoungtong, S. Santon, A. Puangpetch, U. Intusoma, W. Tassaneeyakul, V. Theeramoke P145 HLA-B*38:01 and HLA-A*24:02 allele frequencies in Spanish patients with lamotrigine-induced SCARs Teresa BellĂłn, Elena Ramirez, Alberto Manuel Borobia, Hoi Tong, Jose Luis Castañer, Francisco JosĂ© De Abajo P146 Overrepresentation of a class II HLA haplotype in severe hypersensitivity type I reactions to carboplatin Violeta RĂ©gnier Galvao, Rebecca Pavlos, Elizabeth Mckinnon, Kristina Williams, Alicia Beeghly-Fadiel, Alec Redwood, Elizabeth Phillips, Mariana Castells Poster walk 17: in vivo diagnosis + sIgE (P147âP154) P147 Absence of specific Ig-e against beta-lactams 9 months after an allergic reaction to amoxicillin-clavulanic acid Elisa Boni, Marina Russello, Marina Mauro P148 Drug provocation tests in suspected opioid allergy Kok Loong Ue, Krzysztof Rutkowski P149 Improvement to the specific IgE cut-off in the assess of ÎČ-lactamic allergy Victor Soriano Gomis, Jorge Frances Ferre, Angel Esteban Rodriguez, Vicente CantĂł Reig, Javier Fernandez Sanchez P150 Initial false negative specific IgE to gelatin in a patient with gelatin-induced anaphylaxis Christine Breynaert, Erna Van Hoeyveld, Rik Schrijvers P151 Inmediate reactions to beta-lactam antibiotics: pattern of skin test response over the time Jose Julio Laguna Martinez, Rosario Gonzalez Mendiola, Javier Dionicio Elera, Cosmin Boteanu, Aranzazu Jimenez Blanco, Marta Del Pozo, Raquel Fuentes Irigoyen P152 New fluorescent dendrimeric antigens for the evaluation of dendritic cell maturation as a test to detect allergy reactions to amoxicillin Daniel Collado, Yolanda Vida, Francisco Najera, Ezequiel Perez-Inestrosa, Pablo Mesa-Antunez, Cristobalina Mayorga, MarĂa JosĂ© Torres, Miguel Blanca P153 Positive skin test or positive specific IgE to penicillin does not predict penicillin allergy Line K. Tannert, Charlotte G. Mortz, Per Stahl Skov, Carsten Bindslev-Jensen P154 Significance of skin testing and in vitro-analysis of neuromuscular blocking agents in diagnosis of perioperative drug hypersensitivity: evaluation of a negative control population Wolfgang PfĂŒtzner, Hannah Dörnbach, Johanna Visse, Michele Rauber, Christian Möbs Poster walk 18: in vitro/ex vivo (P155âP158, P160âP164) P155 Diagnostic value of the lymphocyte toxicity assay (LTA) and the in vitro platelet toxicity assay (IPTA) for ÎČ-lactam allergy Abdelbaset A. Elzagallaai, Lindsey Chow, Awatif M. Abuzgaia, Michael J. Rieder P156 Enzyme linked immunospot assay used in the diagnosis of severe cutaneous adverse reactions to antimicrobials Alec Redwood, Jason Trubiano, Rebecca Pavlos, Emily Woolnough, Kaija Stautins, Christina Cheng, Elizabeth Phillips P157 Evaluation of in vitro diagnostic methods for identifying the culprit drugs in drug hypersensitivity Kenichi Kato, Hiroaki Azukizawa, Takaaki Hanafusa, Ichiro Katayama P158 Ex-vivo expanded skin-infiltrating T cells from severe drug eruptions are reactive with causative drugs: a possible novel method for determination of causative drugs Toshiharu Fujiyama, Hideo Hashizume, Takatsune Umayahara, Taisuke Ito, Yoshiki Tokura P160 In vitro release of IL-2, IL-5 and IL-13 in diagnosis of patients with delayed-type nickel hypersensitivity Mira Silar, Mihaela Zidarn, Helena Rupnik, Peter Korosec P161 Single cell analysis of drug responsive T cells; identification of candidate drug reactive T cell receptors in abacavir and carbamazepine hypersensitivity Alec James Redwood, Kaija Strautins, Katie White, Abha Chopra, Katherine Konvinse, Shay Leary, Rebecca Pavlos, Simon Mallal, Elizabeth Phillips P162 Specificity and sensitivity of LTT in DRESS: analysis of agreement with the Spanish pharmacovigilance system probability algorithm Rosario Cabañas, Elena Ramirez, Ana MarĂa Fiandor, Teresa BellĂłn P163 The role of interleukin-22 in ÎČ-lactam hypersensitivity Andrew Sullivan, Paul Whitaker, Daniel Peckham, B. Kevin Park, Dean J. Naisbitt P164 Vancomycin-specific T cell responses and teicoplanin cross-reactivity Wei Yann Haw, Marta E. Polak, Carolann Mcguire, Michael R. Ardern-Jones Poster walk 19: BAT and biomarkers (P165âP173) P165 A combination of early biomarkers useful for the prediction of severe ADRs Yumi Aoyama, Tetsuo Shiohara P166 Basophil activation test in the diagnostic approach of reactions during general anaesthesia Ana Moreira, Susana Cadinha, PatrĂcia Barreira, Ana Castro Neves, Daniela Malheiro, Sara Correia, J. P. Moreira Da Silva P167 IL-10 can be related to successful desensitization Asli Gelincik, Semra Demir, Fatma Sen, Hamza Ugur Bozbey, Muge Olgac, Derya Unal, Raif Coskun, Bahauddin Colakoglu, Suna Buyuozturk, Esin Ăatin-Aktas, Gunnur Deniz P168 Immediate reactions to proton pump inhibitors: value of basophil activation test Maria Salas, Jose Julio Laguna, Esther Barrionuevo, J. Dionicio, Tahia Fernandez, R. Gonzalez-Mendiola, I. Olazabal, Maria Dolores Ruiz, Miguel Blanca, Cristobalina Mayorga, Maria JosĂ© Torres P169 Improvement of the elevated tryptase criterion to discriminate IgE from non-IgE mediated allergic reactions Gabriel Gastaminza, Alberto Lafuente, Carmen DâAmelio, Amalia Bernad, Olga Vega, Roselle Catherine Madamba, M. Jose Goikoetxea, Marta Ferrer, Jorge NĂșñez P170 Low expression of Tim-3 could serve as a biomarker for control and diagnose maculopapular exanthema induced by drugs Tahia Diana FernĂĄndez, Inmaculada Doña, Francisca Palomares, RubĂ©n FernĂĄndez, Maria Salas, Esther Barrionuevo, Maria Isabel Sanchez, Miguel Blanca, Maria JosĂ© Torres, Cristobalina Mayorga P171 Role of basophil activation test using two different activation markers for the diagnosis of allergy to fluoroquinolones Esther Barrionuevo, TahĂa Fernandez, Arturo Ruiz, Adriana Ariza, Maria Salas, Inmaculada Doña, Ana Molina, Miguel Blanca, Maria Jose Torres, Cristobalina Mayorga P172 The importance of basophil activation test in anaphylaxis due to celecoxib Amalia Bernad Alonso, Carmen DâAmelio GarĂłfalo, Olga Vega Matute, Marta Ferrer Puga, MarĂa JosĂ© Goikoetxea Lapresa, Roselle Catherine Yu Madamba, Gabriel Gastaminza Lasarte P173 The role of basophil activation test in the diagnosis of immediate type drug hypersensitivity to betalactam antibiotics Antonia Thinnes, Hans F. Merk, Jens Malte Baron, Martin Leverkus, Galina Balakirski Poster walk 20: TCR recognition, cellular (P174âP183) P174 Characterisation of the effect of co-inhibitory signalling on the activation of drug-derived antigen-specific T-cells Andrew Gibson, Monday Ogese, Lee Faulkner, B. Kevin Park, Dean J. Naisbitt P175 Characterization of drug hapten-specific T cell responses in piperacillin hypersensitive patients Zaid Al-Attar, Fiazia Yaseen, Xiaoli Meng, Rozalind Jenkins, Paul Whitaker, Daniel Peckham, Lee Faulkner, John Farrel, Kevin Park, Dean Naisbitt P176 Characterization of the response of T-cells to telaprevir and its metabolite in normal volunteers Zaid Al-Attar, Khetam Alhilali, Yanni Xue, John Farrell, Lee Faulkner, Kevin Park, Dean Naisbitt P177 Characterization of the T cell receptor signatures of drug-responsive T cells Patricia Illing, Nicole Mifsud, Heidi Fettke, Jeffrey Lai, Rebecca Ho, Patrick Kwan, Anthony Purcell P178 Defining the signals between hepatocytes and immune cells in idiosyncratic drug-induced liver injury (DILI) Monday O. Ogese, Lee Faulkner, B. Kevin Park, Catherine Betts, Dean J. Naisbitt P179 Development of novel chemicals that do not bind to HLA-B*57:01 or activate CD8 + T-cells through modification of the 6-amino cyclopropyl group of abacavir Paul Thomson, John Farrell, Mohammad Alhaidari, Neill Berry, Paul M. OâNeill, B. Kevin Park, Dean J. Naisbitt P180 Generation and characterization of dapsone- and nitroso-dapsone-specific T-cell clones using lymphocytes from healthy volunteers Abdulaziz Alzahrani, Monday O. Ogese, John Farrell, Lee Faulkner, Andrew Gibson, Arun Tailor, B. Kevin Park, Dean J. Naisbitt P181 Identification of benzylpenicillin-hapten peptides responsible for naĂŻve T-cell activation and immunization of allergic patients to penicillin Marie Eliane Azoury, Lucia Fili, Rami Bechara, NoĂ©mie Scornet, Cathy Nhim, Richard Weaver, Nancy Claude, Delphine Joseph, Bernard Maillere, Paola Parronchi, Marc Pallardy P182 Massive expansion of clonotypic and polycytotoxic CD8+ T cells in toxic epidermal necrolysis Axel Patrice Villani, Aurore RoziĂšres, BenoĂźt BensaĂŻd, Mathilde Tardieu, Floriane Albert, Virginie Mutez, Tugba Baysal, Marc Pallardy, Janet Maryanski, Jean-François Nicolas, Osami Kanagawa, Marc Vocanson P183 Pharmaco-immunological synapse of HLA-drug-TCR in SCAR Shuen-Iu Hung Poster walk 21: new in vitro methods, haptens, etc. (P184âP194) P184 Amoxicillin-clavulanate forms distinct multiple haptenic structures on human serum albumin in patients Xiaoli Meng, Arun Tailor, Caroline J. Harrison, Rosalind E. Jenkins, Paul Whitaker, Neil S. French, Dean J. Naisbitt, B. Kevin Park P185 Dendrimeric antigens for studying the influence of penicillin determinants orientation on IgE recognition Maria Isabel Montañez, Cristobalina Mayorga, Francisco Najera, Adriana Ariza, Tahia D. Fernandez, Maria Salas, Angela Martin-Serrano, Miguel Blanca, Ezequiel Perez-Inestrosa, Maria Jose Torres P186 Dendrimeric antigens on solid supports: designed materials for IgE quantification Yolanda Vida, Maria Isabel Montañez, Noemi Molina, Daniel Collado, Francisco Najera, Adriana Ariza, Maria Jose Torres, Cristobalina Mayorga, Ezequiel Perez-Inestrosa P187 Development of a screening assay for drug hypersensitivity using naĂŻve T cells from donors with seven different HLA class I risk alleles Lee Faulkner, Sally Wood, Ana Alfirevic, Munir Pirmohamed, Dean J. Naisbitt, B. Kevin Park P188 Different patterns of recognition of structures derived from amoxicillin by IgE antibodies from patients with immediate hypersensitivity reactions to betalactams Adriana Ariza, Cristobalina Mayorga, MarĂa Isabel Montañez, MarĂa Salas, Inmaculada Doña, Ăngela MartĂn-Serrano, Ezequiel PĂ©rez-Inestrosa, Dolores PĂ©rez-Sala, Miguel Blanca, Antonio E. GuzmĂĄn, MarĂa JosĂ© Torres P189 High-resolution typing of HLA polymorphism and T-cell receptor repertoire for severe adverse drug reactions based on the cost-effective next-generation sequencing approaches Tai-Ming Ko, Yuan-Tsong Chen, Jer-Yuarn Wu P190 Identification and fate of intracellular proteins haptenated by amoxicillin Francisco J. SĂĄnchez-GĂłmez, Juan M. GonzĂĄlez-Morena, Yolanda Vida, Ezequiel PĂ©rez-Inestrosa, Miguel Blanca, MarĂa J. Torres, Dolores PĂ©rez-Sala P191 In vitro detection of terbinafine protein adducts Arun Tailor, Toru Usui, Yanni Xue, Xiaoli Meng, Dean J. Naisbitt, B. Kevin Park P192 MicroRNAs dysregulation in PBMCs from drug hypersensitivity patients during drug challenge in vitro Alejandra Monroy Arreola, Jesus Agustin Badillo Corona, Silvia Mendez Flores, Judith Dominguez Cherit, Dean J. Naisbitt, Noe Valentin Duran Figueroa, Jose Luis Castrejon Flores P193 NSAIDs-exacerbated cutaneous disease: high throughput gene expression profiling JosĂ© Antonio Cornejo-GarcĂa, James Perkins, Natalia Blanca-LĂłpez, Diana PĂ©rez-Alzate, Raquel Jurado-Escobar, Inmaculada Doña, Gador Bogas, MarĂa J. Torres, Gabriela Canto, Miguel Blanca P194 Utility of skin tests in non-immediate reactions to amoxicillin Luis Mario Tubella Marti, Fernando Pineda De La Losa, Francisca Arribas Poves, Jaime Tubella Lopez, Teodora Lopez Santiag