Author: "Ofure Obazee" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Ofure Obazee"' showing total 29 results

Start Over Author "Ofure Obazee"

29 results on '"Ofure Obazee"'

1. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: Alison P. Klein, Brian M. Wolpin, Harvey A. Risch, Rachael Z. Stolzenberg-Solomon, Evelina Mocci, Mingfeng Zhang, Federico Canzian, Erica J. Childs, Jason W. Hoskins, Ashley Jermusyk, Jun Zhong, Fei Chen, Demetrius Albanes, Gabriella Andreotti, Alan A. Arslan, Ana Babic, William R. Bamlet, Laura Beane-Freeman, Sonja I. Berndt, Amanda Blackford, Michael Borges, Ayelet Borgida, Paige M. Bracci, Lauren Brais, Paul Brennan, Hermann Brenner, Bas Bueno-de-Mesquita, Julie Buring, Daniele Campa, Gabriele Capurso, Giulia Martina Cavestro, Kari G. Chaffee, Charles C. Chung, Sean Cleary, Michelle Cotterchio, Frederike Dijk, Eric J. Duell, Lenka Foretova, Charles Fuchs, Niccola Funel, Steven Gallinger, J. Michael M. Gaziano, Maria Gazouli, Graham G. Giles, Edward Giovannucci, Michael Goggins, Gary E. Goodman, Phyllis J. Goodman, Thilo Hackert, Christopher Haiman, Patricia Hartge, Manal Hasan, Peter Hegyi, Kathy J. Helzlsouer, Joseph Herman, Ivana Holcatova, Elizabeth A. Holly, Robert Hoover, Rayjean J. Hung, Eric J. Jacobs, Krzysztof Jamroziak, Vladimir Janout, Rudolf Kaaks, Kay-Tee Khaw, Eric A. Klein, Manolis Kogevinas, Charles Kooperberg, Matthew H. Kulke, Juozas Kupcinskas, Robert J. Kurtz, Daniel Laheru, Stefano Landi, Rita T. Lawlor, I.-Min Lee, Loic LeMarchand, Lingeng Lu, Núria Malats, Andrea Mambrini, Satu Mannisto, Roger L. Milne, Beatrice Mohelníková-Duchoňová, Rachel E. Neale, John P. Neoptolemos, Ann L. Oberg, Sara H. Olson, Irene Orlow, Claudio Pasquali, Alpa V. Patel, Ulrike Peters, Raffaele Pezzilli, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Ghislaine Scelo, Howard D. Sesso, Gianluca Severi, Xiao-Ou Shu, Debra Silverman, Jill P. Smith, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Francesca Tavano, Mark D. Thornquist, Geoffrey S. Tobias, Stephen K. Van Den Eeden, Yogesh Vashist, Kala Visvanathan, Pavel Vodicka, Jean Wactawski-Wende, Zhaoming Wang, Nicolas Wentzensen, Emily White, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Peter Kraft, Donghui Li, Stephen Chanock, Ofure Obazee, Gloria M. Petersen, and Laufey T. Amundadottir
Subjects: Science
Abstract: Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.
Published: 2018
Full Text: View/download PDF

2. Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer

Author: Manuel Gentiluomo, Luca Morelli, Ofure Obazee, Daniele Campa, Federico Canzian, Justo Lorenzo-Bermejo, and Ye Lu
Subjects: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, pancreatic cancer, Type 2 diabetes, Adenocarcinoma, Polymorphism, Single Nucleotide, Body Mass Index, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, genetic polymorphisms, Pancreatic cancer, Internal medicine, Mendelian randomization, Genetics, medicine, Humans, Insulin, risk factors, Genetic Predisposition to Disease, Obesity, Genetics (clinical), Aged, Genetic association, business.industry, Mendelian Randomization Analysis, Middle Aged, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Cohort, Female, Observational study, business, Body mass index, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study
Abstract: BackgroundObservational studies have reported multiple risk factors for pancreatic ductal adenocarcinoma (PDAC). Some are well established, like tobacco smoking, alcohol drinking, obesity and type 2 diabetes, whereas some others are putative, such as allergy and dietary factors. Identifying causal risk factors can help establishing those that can be targeted to contribute to prevent PDAC.ObjectiveWe sought to investigate the possible causal effects of established and putative factors on PDAC risk.MethodsWe conducted a two-sample Mendelian randomisation (MR) study using publicly available data for genetic variants associated with the factors of interest, and summary genetic data from genome-wide association studies of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including in total 8769 cases and 7055 controls. Causality was assessed using inverse-variance weighted, MR-Egger regression and weighted median methods, complemented with sensitivity and radial MR analyses.ResultsWe found evidence for a causal effect of body mass index (BMI) on PDAC risk (OR 1.43, 95% CI 1.20 to 1.71, p=8.43×10−5). Fasting insulin (OR 2.84, 95% CI 1.23 to 6.56, p=0.01), low-density lipoprotein cholesterol (OR 1.16, 95% CI 1.02 to 1.32, p=0.03) and type 2 diabetes (OR 1.09, 95% CI 1.01 to 1.17, p=0.02) were also causally associated with PDAC risk. BMI showed both direct and fasting insulin-mediated causal effects.ConclusionWe found strong evidence that BMI is causally associated with PDAC risk, providing support that obesity management may be a potential prevention strategy for reducing pancreatic cancer risk while fasting insulin and type 2 diabetes showed a suggestive association that should be further investigated.
Published: 2020
Full Text: View/download PDF

3. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

Author: Verena Katzke, Rita T. Lawlor, Ugo Boggi, Paola Fogar, Livia Archibugi, George Theodoropoulos, Beatrice Mohelnikova-Duchonova, C. E. Radu, Giulia Martina Cavestro, Christos Dervenis, Francesca Federici, Federico Canzian, Jakob R. Izbicki, Claudio Pasquali, Aldo Scarpa, Valerio Pazienza, Péter Hegyi, Renata Talar-Wojnarowska, Frank Bergmann, Thomas Pausch, Stefano Landi, Maurizio Cantore, Stig E. Bojesen, Theron Johnson, Oliver Strobel, Ewa Małecka-Panas, Thilo Hackert, Angelo Andriulli, Audrius Ivanauskas, Benny V. Jensen, J. Kaiser, Daniele Campa, Andrea Mambrini, Orazio Palmieri, Gabriele Capurso, Ludmila Vodickova, Maria Gazouli, Evaristo Maiello, Roberto Salvia, Elżbieta Iskierka-Jażdżewska, Christine Tjaden, Rudolph Kaaks, M. Di Leo, Anna Caterina Milanetto, Pavel Soucek, Daniela Basso, Julia S. Johansen, H Brenner, Raffaele Pezzilli, Katarina Cuk, Ofure Obazee, Cosimo Sperti, Pavel Vodicka, Juozas Kupcinskas, Kai Uwe Saum, Yogesh K. Vashist, G. Delle Fave, Andrea Szentesi, Cristian Gheorghe, Radmila Lemstrová, and Inna Chen
Subjects: Oncology, Cancer Research, Mutation, medicine.medical_specialty, Pancreatic disease, business.industry, Disease, Odds ratio, medicine.disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, medicine, Family history, business, Risk assessment, CHEK2
Abstract: Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values
Published: 2019
Full Text: View/download PDF

4. Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer

Author: Alfonso Méndez-Tenorio, María Mercedes Bravo, Federico Canzian, Esperanza Trujillo, Javier Torres, Ofure Obazee, Ikuko Kato, Margarita Camorlinga-Ponce, Angelika Stein, and Cosmeri Rizzato
Subjects: 0301 basic medicine, medicine.medical_specialty, Genomic Islands, Atrophic gastritis, Chronic gastritis, Virulence, lcsh:Medicine, Biology, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, medicine, CagA, Humans, Nucleotide Motifs, lcsh:Science, Bacterial genomics, Metaplasia, Multidisciplinary, Polymorphism, Genetic, Acute Gastritis, Helicobacter pylori, lcsh:R, Intestinal metaplasia, Genetic Variation, Sequence Analysis, DNA, medicine.disease, biology.organism_classification, 030104 developmental biology, Latin America, 030220 oncology & carcinogenesis, Gastritis, Disease Progression, lcsh:Q, medicine.symptom, Gastric cancer, Genome, Bacterial
Abstract: Helicobacter pylori (HP) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Increased virulence in HP isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagPAI). We analyzed the microvariants in cagPAI genes with the hypothesis that they may play an important role in determining HP virulence. We tested DNAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (CG, N = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.
Published: 2020

5. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

Author: John P. Neoptolemos, Markus W. Büchler, Jakob R. Izbicki, Ben Schöttker, Cosmeri Rizzato, Cornelia Schroeder, Salvatore Paiella, Hanneke W. M. van Laarhoven, William Greenhalf, Simona Bursi, Renata Talar-Wojnarowska, Christos Dervenis, Ludmila Vodickova, Francesca Tavano, Giulia Martina Cavestro, Thilo Hackert, Claudio Pasquali, Ewa Małecka-Panas, Gabriele Capurso, Andrea Mambrini, Daniele Campa, Andrea Padoan, Ioannis S. Papanikolaou, Raffaele Pezzilli, Péter Hegyi, Beatrice Mohelnikova-Duchonova, Federica Gemignani, Michael F. Nentwich, Pavel Vodicka, Stefano Landi, Richárd Szmola, Anna Caterina Milanetto, Eithne Costello, Rudolf Kaaks, Laura Ginocchi, Bernd Holleczek, Erika Darvasi, Verena Katzke, Evaristo Maiello, Manuel Gentiluomo, Ondrej Strouhal, Orazio Palmieri, Juozas Kupcinskas, Alice Alessandra Galeotti, Viktor Hlavac, George Theodoropoulos, Audrius Ivanauskas, Maria Gazouli, Ferenc Izbéki, Federico Canzian, Oliver Strobel, Ofure Obazee, Martin Lovecek, Timothy J. Key, Domenica Gioffreda, Pavel Soucek, Ugo Boggi, Krzysztof Jamroziak, Cosimo Sperti, Maarten F. Bijlsma, Yogesh K. Vashist, Andrea Szentesi, Hermann Brenner, Livia Archibugi, Giuseppe Vanella, Daniela Basso, Radiotherapy, Center of Experimental and Molecular Medicine, CCA - Cancer Treatment and Quality of Life, Oncology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Galeotti, A. A., Gentiluomo, M., Rizzato, C., Obazee, O., Neoptolemos, J. P., Pasquali, C., Nentwich, M., Cavestro, G. M., Pezzilli, R., Greenhalf, W., Holleczek, B., Schroeder, C., Schottker, B., Ivanauskas, A., Ginocchi, L., Key, T. J., Hegyi, P., Archibugi, L., Darvasi, E., Basso, D., Sperti, C., Bijlsma, M. F., Palmieri, O., Hlavac, V., Talar-Wojnarowska, R., Mohelnikova-Duchonova, B., Hackert, T., Vashist, Y., Strouhal, O., Van Laarhoven, H., Tavano, F., Lovecek, M., Dervenis, C., Izbeki, F., Padoan, A., Malecka-Panas, E., Maiello, E., Vanella, G., Capurso, G., Izbicki, J. R., Theodoropoulos, G. E., Jamroziak, K., Katzke, V., Kaaks, R., Mambrini, A., Papanikolaou, I. S., Szmola, R., Szentesi, A., Kupcinskas, J., Bursi, S., Costello, E., Boggi, U., Milanetto, A. C., Landi, S., Gazouli, M., Vodickova, L., Soucek, P., Gioffreda, D., Gemignani, F., Brenner, H., Strobel, O., Buchler, M., Vodicka, P., Paiella, S., Canzian, F., and Campa, D.
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Multifactorial Inheritance, Pancreatic disease, genetic epidemiology, Population, Single-nucleotide polymorphism, Disease, pancreas and biliary tract, Polymorphism, Single Nucleotide, Risk Assessment, ABO Blood-Group System, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Pancreatic cancer, Internal medicine, Genetics, medicine, oncology, Humans, education, Genetics (clinical), Alleles, Early Detection of Cancer, Genetic association, education.field_of_study, business.industry, medicine.disease, Pancreatic Neoplasms, 030104 developmental biology, Genetic epidemiology, 030220 oncology & carcinogenesis, Cohort, Female, business, Carcinoma, Pancreatic Ductal
Abstract: BackgroundMost cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.ObjectiveWe generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.MethodsWe tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.ResultsThe scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10−10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10−8, highest vs lowest quintile of the weighted multifactorial score).ConclusionWe found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
Published: 2020

6. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Author: William R. Bamlet, Alpa V. Patel, Mingfeng Zhang, Eric J. Jacobs, Tongwu Zhang, Evelina Mocci, Demetrius Albanes, Nilanjan Chatterjee, Alan A. Arslan, Phyllis J. Goodman, Wenming Xiao, Irene Collins, Ghislaine Scelo, Howard D. Sesso, Manolis Kogevinas, Lang Wu, Patricia Hartge, Manal Hasan, Jill P. Smith, Herbert Yu, Laufey T. Amundadottir, Geoffrey S. Tobias, Nathaniel Rothman, Jean Wactawski-Wende, Mengmeng Du, Edward Giovannucci, Stephen K. Van Den Eeden, Roger L. Milne, Irene Orlow, Elizabeth A. Holly, Kathy J. Helzlsouer, Miquel Porta, Ulrike Peters, Harvey A. Risch, Eric J. Duell, Steven Gallinger, Paige M. Bracci, Charles Kooperberg, Michael Goggins, Federico Canzian, Antonia Trichopoulou, Lei Song, Robert J. Kurtz, Brian M. Wolpin, Anne Zeleniuch-Jacquotte, Stephen J. Chanock, Gianluca Severi, Christopher A. Haiman, Loic LeMarchand, Ann L. Oberg, Jason W. Hoskins, Alison P. Klein, Kala Visvanathan, Gary E. Goodman, Gabriella Andreotti, Donghui Li, Charles C. Chung, Michelle Cotterchio, Lauren K. Brais, Satu Männistö, Núria Malats, Jianxin Shi, Charles S. Fuchs, Wei Zheng, Peter Kraft, Robert N. Hoover, J. Michael Gaziano, Erica J. Childs, Nicolas Wentzensen, Kai Yu, Paul Brennan, Mark D. Thornquist, Julie E. Buring, Anne Tjønneland, Jun Zhong, Kevin M. Brown, Ofure Obazee, Rachael Z. Stolzenberg-Solomon, Sabina Sieri, Bas Bueno-de-Mesquita, Debra T. Silverman, Ana Babic, Sonja I. Berndt, Chen Yuan, Ayelet Borgida, Rachel E. Neale, Eric A. Klein, Gloria M. Petersen, Xiao-Ou Shu, Kimmie Ng, Ashley Jermusyk, Graham G. Giles, Laura Beane-Freeman, Emily White, Malin Sund, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Subjects: 2. Zero hunger, Genetics, 0303 health sciences, Cancer Research, Candidate gene, [SDV]Life Sciences [q-bio], Genome-wide association study, Quantitative trait locus, Biology, medicine.disease, 3. Good health, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Pancreatic cancer, Genotype, medicine, PDX1, Pancreas, 030304 developmental biology
Abstract: Background Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74–421 samples). Results We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
Published: 2020
Full Text: View/download PDF

7. Genome-wide association study identifies an early onset pancreatic cancer risk locus

Author: Verena Katzke, Jakob R. Izbicki, Francesca Tavano, Rita T. Lawlor, Thilo Hackert, Raffaella Alessia Zuppardo, Giulia Martina Cavestro, Federico Canzian, Frederike Dijk, Martin Oliverius, George Theodoropoulos, Pavel Soucek, Manuel Gentiluomo, Rudolf Kaaks, Erika Darvasi, Yogesh K. Vashist, Bill Greenhalf, Juozas Kupcinskas, Maurizio Lucchesi, Borislav Rusev, Andrea Szentesi, Gabriele Capurso, Ewa Małecka-Panas, Lucia Moletta, Beatrice Mohelnikova-Duchonova, Franco Bambi, Ugo Boggi, Alba Ballerini, Krzysztof Jamroziak, Ben Schöttker, Simona Bursi, Raffaele Pezzilli, Gyula Farkas, Dania Bozzato, Áron Vincze, Stefano Landi, Anna Caterina Milanetto, Péter Hegyi, Michael F. Nentwich, Laura Ginocchi, Pavel Vodicka, Stefania Moz, Ludmila Vodickova, Hermann Brenner, Olivier R. Busch, Viktor Hlavac, Audrius Ivanauskas, John P. Neoptolemos, Domenica Gioffreda, Ofure Obazee, Livia Archibugi, Nathalia A. Giese, Giuseppe Vanella, Xin Gao, Renata Talar-Wojnarowska, Angelo Andriulli, Oliver Strobel, Daniele Campa, Maria Gazouli, Pathology, CCA - Cancer biology and immunology, Surgery, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, AGEM - Re-generation and cancer of the digestive system, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Campa, D., Gentiluomo, M., Obazee, O., Ballerini, A., Vodickova, L., Hegyi, P., Soucek, P., Brenner, H., Milanetto, A. C., Landi, S., Gao, X., Bozzato, D., Capurso, G., Tavano, F., Vashist, Y., Hackert, T., Bambi, F., Bursi, S., Oliverius, M., Gioffreda, D., Schottker, B., Ivanauskas, A., Mohelnikova-Duchonova, B., Darvasi, E., Pezzilli, R., Malecka-Panas, E., Strobel, O., Gazouli, M., Katzke, V., Szentesi, A., Cavestro, G. M., Farkas, G., Izbicki, J. R., Moz, S., Archibugi, L., Hlavac, V., Vincze, A., Talar-Wojnarowska, R., Rusev, B., Kupcinskas, J., Greenhalf, B., Dijk, F., Giese, N., Boggi, U., Andriulli, A., Busch, O. R., Vanella, G., Vodicka, P., Nentwich, M., Lawlor, R. T., Theodoropoulos, G. E., Jamroziak, K., Zuppardo, R. A., Moletta, L., Ginocchi, L., Kaaks, R., Neoptolemos, J. P., Lucchesi, M., and Canzian, F.
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Pancreatic disease, pancreatic cancer, early onset, Single-nucleotide polymorphism, Genome-wide association study, very early onset pancreatic cancer, Polymorphism, Single Nucleotide, 03 medical and health sciences, single nucleotide polymorphisms, 0302 clinical medicine, Risk Factors, Pancreatic cancer, Internal medicine, Genetic predisposition, Medicine, Humans, Genetic Predisposition to Disease, Genetic variability, Pancreas, Genetic association, genome-wide association study, business.industry, Middle Aged, medicine.disease, Pancreatic Neoplasms, 030220 oncology & carcinogenesis, Case-Control Studies, Female, Age of onset, business, Carcinoma, Pancreatic Ductal
Abstract: Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1x10-4 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset≤50, and 4142 controls from the PANDoRA consortium while in the in silico data we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15x10-4 ). In conclusion we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature. This article is protected by copyright. All rights reserved.
Published: 2020

8. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

Author: Rudolf Kaaks, Thilo Hackert, Federico Canzian, Livia Archibugi, H. Bas Bueno-de-Mesquita, Angelo Andriulli, Juozas Kupcinskas, Kai Uwe Saum, Yogesh K. Vashist, Andrea Mambrini, Kay-Tee Khaw, Andrea Szentesi, Rita T. Lawlor, Laimas Virginijus Jonaitis, Domenica Gioffreda, Raffaele Pezzilli, Katarina Cuk, Daniela Basso, Ludmila Vodickova, Claudio Pasquali, Pavel Vodicka, Oliver Strobel, Martin Lovecek, Péter Hegyi, Chiara Valsuani, Krzysztof Jamroziak, Gabriele Capurso, Renata Talar-Wojnarowska, Martina Matarazzi, Jakob R. Izbicki, Niccola Funel, Hanneke W. M. van Laarhoven, Pavel Soucek, Daniele Campa, Beatrice Mohelnikova-Duchonova, Francesca Federici, Hermann Brenner, Franco Bambi, Anna Katharina König, Carlo Federico Zambon, Verena Katzke, Maarten F. Bijlsma, William Greenhalf, Francesca Tavano, Felice Pirozzi, Gianfranco Delle Fave, Ofure Obazee, Cosimo Sperti, Jörg Kaiser, Giulia Martina Cavestro, Timothy J. Key, and Stefano Landi
Subjects: Genetics, Oncology, Cancer Research, medicine.medical_specialty, Pancreatic disease, Cancer, Single-nucleotide polymorphism, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Genetic marker, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, Mendelian randomization, medicine, SNP, Risk assessment
Abstract: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.
Published: 2018
Full Text: View/download PDF

9. Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high-grade premalignant gastric lesions

Author: Elena Kasamatsu, Angelika Stein, Margarita Camorlinga-Ponce, Federico Canzian, Lourdes Flores-Luna, Ofure Obazee, Nubia Muñoz, Ikuko Kato, Javier Torres, Alfonso Méndez-Tenorio, Hyejong Jang, Esperanza Trujillo, María Mercedes Bravo, Cosmeri Rizzato, Jorge Vivas, and Wei Chen
Subjects: Adult, DNA, Bacterial, Genetic Markers, Male, Cancer Research, medicine.medical_specialty, Genomic Islands, Biopsy, Population, Biology, Colombia, Gastroenterology, Risk Assessment, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Risk Factors, Stomach Neoplasms, Internal medicine, medicine, CagA, Humans, education, Stomach cancer, Mexico, education.field_of_study, Antigens, Bacterial, Metaplasia, Polymorphism, Genetic, Helicobacter pylori, Whole Genome Sequencing, Stomach, Intestinal metaplasia, Cancer, Middle Aged, biology.organism_classification, medicine.disease, medicine.anatomical_structure, Oncology, Gastric Mucosa, 030220 oncology & carcinogenesis, Gastritis, Female, medicine.symptom, Precancerous Conditions, Genome, Bacterial
Abstract: Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.
Published: 2019

10. Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium

Author: Rudolf Kaaks, Stefano Landi, Felice Pirozzi, Luca Landoni, Ofure Obazee, William Greenhalf, Daniela Basso, Eithne Costello, Gabriele Capurso, Oliver Strobel, Francesca Tavano, Timothy J. Key, Federico Canzian, Claudio Pasquali, Rita T. Lawlor, Domenica Gioffreda, Franco Bambi, John P. Neoptolemos, Kay-Tee Khaw, Renata Talar-Wojnarowska, Daniele Campa, Vincenzo Corbo, Carlo Federico Zambon, Verena Katzke, Francesco Panzuto, Valbona Liço, Manuela Pastore, Krzysztof Jamroziak, Thilo Hackert, Carlo Lombardo, Giulia Zerboni, and Anna Caterina Milanetto
Subjects: 0301 basic medicine, medicine.medical_specialty, Pancreatic disease, Single-nucleotide polymorphism, Context (language use), Neuroendocrine tumors, Biology, Bioinformatics, polymorphism, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, neuroendocrine tumors, epidemiology, medicine, Humans, Genetic Predisposition to Disease, pancreatic endocrine tumors, Genetic association, Aged, Cancer, Middle Aged, medicine.disease, Pancreatic Neoplasms, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Etiology, epidemiology, neuroendocrine tumors
Abstract: Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms for which very little is known about either environmental or genetic risk factors. Only a handful of association studies have been performed so far, suggesting a small number of risk loci. Methods: To replicate the best findings, we have selected 16 SNPs suggested in previous studies to be relevant in PNET etiogenesis. We genotyped the selected SNPs (rs16944, rs1052536, rs1059293, rs1136410, rs1143634, rs2069762, rs2236302, rs2387632, rs3212961, rs3734299, rs3803258, rs4962081, rs7234941, rs7243091, rs12957119, and rs1800629) in 344 PNET sporadic cases and 2,721 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium. Results: After correction for multiple testing, we did not observe any statistically significant association between the SNPs and PNET risk. We also used three online bioinformatic tools (HaploReg, RegulomeDB, and GTEx) to predict a possible functional role of the SNPs, but we did not observe any clear indication. Conclusions: None of the selected SNPs were convincingly associated with PNET risk in the PANDoRA consortium. Impact: We can exclude a major role of the selected polymorphisms in PNET etiology, and this highlights the need for replication of epidemiologic findings in independent populations, especially in rare diseases such as PNETs. Cancer Epidemiol Biomarkers Prev; 26(8); 1349–51. ©2017 AACR.
Published: 2019
Full Text: View/download PDF

11. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author: Bertrand Joly, Hagay Sobol, Isabelle Azais, Hervé Avet-Loiseau, Karine Augeul-Meunier, Catherine Le Bris, Delphine Demangel, Maroulio Pertesi, Xavier Leleu, Maria Victoria Revuelta, Maxime Vallée, Manuel Cliquennois, James D. McKay, Aurore Perrot, Aleksandra Butrym, Matthieu Foll, Björn Nilsson, Javier Oliver, Judit Várkonyi, Emeline Perrial, Xiaomu Wei, Artur Jurczyszyn, Gabriele Buda, Marcin Rymko, Cécile Leyronnas, Robert J. Klein, Elżbieta Iskierka-Jażdżewska, Claire Mathiot, Marzena Wątek, Eric Voog, Olivier Decaux, Florence Desquesnes, Jill Corre, Arnon Nagler, Jean Gabriel Fuzibet, Véronique Dorvaux, Jan Maciej Zaucha, Philippe Rodon, Siwei Chen, Denis Caillot, Laurent Garderet, Michel Maigre, Isabelle Leduc, Fabienne Lesueur, Borhane Slama, Sophie Rigaudeau, Philippe Mineur, Norbert Grząśko, Perrine Galia, Rui Manuel Reis, Federico Canzian, Philippe Helias, Yves-Jean Bignon, Marcin Kruszewski, Victor Moreno, Juan Sainz, Nathalie Cheron, Laurent Voillat, Charles Dumontet, Christian Berthou, Marie Beaumont, Brigitte Pegourie, Etienne Paubelle, Marguerite Vignon, Matteo Pelosini, Philippe Casassus, Isabelle Lambrecht, Laure Vincent, Eileen M Boyle, Annette Juul Vangsted, Pascal Bourquard, Laurent Mosser, Margaret Macro, Gerald Marit, Daniele Campa, Brigitte Kolb, Bruno Royer, Jean Fontan, Ramón García-Sanz, Philippe Moreau, Serge Leyvraz, Malgorzata Krawczyk-Kulis, Krzysztof Jamroziak, Joaquin Martinez-Lopez, Bruno Anglaret, Steven M. Lipkin, Nicole Frenkiel, Ofure Obazee, Marek Dudziński, Pascale Cony-Makhoul, Hervé Naman, Andres Jerez, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Genetic Cancer Susceptibility, Department of Biological Statistics and Computational Biology, Cornell University, Weill Medical College of Cornell University Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University [New York], Hospices Civils de Lyon (HCL), ProfileXpert, Université de Lyon, LCMT, ProfileXpert, Biomedical Research Institute of Málaga (IBIMA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMR S1146, Laboratoire d'Imagerie Biomédicale, France, parent, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne [CHU Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Centre Jean Bernard [Le Mans] (Institut Inter-Régional de Cancérologie), CHU de Fort de France (Service Post-Urgences, Pôle RASSUR), CHU de Fort de France, Hôpital JeanMinjoz, Centre hospitalier de Chartres (Chartres) (Service d'Hémato-Oncologie), Service hématologie (CHU d'Amiens), CHU Amiens-Picardie, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], CHU Saint Louis [APHP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Interne [CHU Nice] (Hôpital l'Archet), Hôpital l'Archet-Centre Hospitalier Universitaire de Nice (CHU de Nice), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hematology Department - Namur Thrombosis and Hemostasis Center (NTHC), UCL Mont-Godinne, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHUV, Lausanne (Departement d'Oncologie), Unité d'Oncologie Médicale, Rodez (Hôpital Jacques Puel, Pôle Medical 2), Unité de coordination en oncogériatrie de Basse-Normandie [Caen] (UCOG Basse-Normandie), CHI Poissy-Saint-Germain, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CHG Abbeville (Hématologie), Institut Daniel Hollard [Grenoble], Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Intergroupe francophone du myélome (IFM), Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, Service Hématologie, CH LYON SUD, Pierre benite, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital Sud-Fancilien, CH Sud-Fancilien, Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU de Nîmes), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie, Oncologie Médicale, Centre Azureen de cancérologie, Centre Azureen de cancérologie, Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles (CHV), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [Reims], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Hospitalier et Universitaire de Pointe-à-Pitre (Oncologie Médicale), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], Barretos Cancer Hospital [São Paulo, Brazil], Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary, Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Departement of Hematology, University Hospital, Bydgoszcz, Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Department of Hematology, Jagiellonian University - Medical College, Gdynia Oncology Center, Gdynia and Department of Oncological Propedeutics, Genomic Oncology Area (GENYO), Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Department of Hematology, Insitute of Hematology and Transfusion Medicine, Warsa, Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Department of Hematology, Medical University of Lodz, Departement of Experimental Hemato-Oncology, Medical University of Lubli (Polish Myeloma Study Group), Servicio de Hematología, Hospital Universitario 12 de Octubre [Madrid], Hematology and Medical Oncology Department, Hospital Morales Meseguer, Murcia (IMIB), Department of Biology, University of Pisa, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology Department, Teaching Hospital No1, Rzeszow, Teaching Hospital N°1, Haematology Department, University Hospital of Salamanca, Hematology Division Chaim Sheba Medical Center, Tel Hashomer, Department of Hematology Copernicus Hospital, Torun, Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Wroclaw Medical University, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), INSERM 1052, CNRS 5286, CRCL Lyon, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UPS), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Charleroi (Hématologie et pathologies de la coagulation), Centre Hospitalier Universitaire de Charleroi, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie Génétique, de Prévention et Dépistage, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Département Universitaire Nice (Internal Medicine Department), Hôpital de Nice, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13), Laboratoire de diagnostic génétique et moléculaire, Centre Jean Perrin, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Dijon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génomique du myélome [IUCT Oncopole, Toulouse], IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIBER de Epidemiología y Salud Pública (CIBERESP), Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, Molecular Oncology Research Center [São Paulo, Brazil], Centro de Genomica e Investigacion Oncologica (GENYO), Hospital universitario 12 de Octubre, Holycross Cancer Center of Kielce, Hematology Clinic, Department of Laboratory Medicine Lunds University Hospital Lund, Cornell University [New York], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Laboratoire d'Hématologie [CHU Amiens], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier de Versailles André Mignot (CHV), Instituto de Salud Carlos III [Madrid] (ISC), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Lund University [Lund], Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université catholique de Lille (UCL), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Pisa - Università di Pisa, Mines Paris - PSL (École nationale supérieure des mines de Paris), Wrocław Medical University, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, Letter, [SDV]Life Sciences [q-bio], MEDLINE, Library science, Myeloma, World health, 03 medical and health sciences, 0302 clinical medicine, Multiple myeloma, immune system diseases, Political science, hemic and lymphatic diseases, Exome Sequencing, Genetics, Humans, Exome, Genetic Predisposition to Disease, Cancer genetics, Exome sequencing, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Exosome Multienzyme Ribonuclease Complex, Extramural, Mieloma múltiple, French, Hematology, language.human_language, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], Exome/genetics, Exosome Multienzyme Ribonuclease Complex/genetics, Female, Genetic Predisposition to Disease/genetics, Germ-Line Mutation/genetics, Multiple Myeloma/genetics, Whole Exome Sequencing/methods, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Donation, language, Multiple Myeloma, Genètica, International agency
Abstract: French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization
Published: 2019
Full Text: View/download PDF

12. Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study

Author: Claudio Pasquali, Raffaele Pezzilli, Katarina Cuk, Krzysztof Jamroziak, Gabriele Capurso, Pavel Vodicka, Timothy J. Key, Giulia Martina Cavestro, Kai Uwe Saum, Yogesh K. Vashist, Oliver Strobel, Martin Lovecek, H. Bas Bueno-de-Mesquita, Andrea Szentesi, Ofure Obazee, Angelo Andriulli, Andrea Mambrini, Cosimo Sperti, Kay-Tee Khaw, Rita T. Lawlor, Jörg Kaiser, Federico Canzian, Hanneke W. M. van Laarhoven, Livia Archibugi, Renata Talar-Wojnarowska, Martina Matarazzi, Jakob R. Izbicki, Gianfranco Delle Fave, Daniele Campa, Felice Pirozzi, Francesca Federici, Carlo Federico Zambon, Anna Katharina König, Thilo Hackert, Péter Hegyi, Chiara Valsuani, Stefano Landi, Hermann Brenner, Laimas Virginijus Jonaitis, Beatrice Mohelnikova-Duchonova, Franco Bambi, Domenica Gioffreda, Rudolf Kaaks, Niccola Funel, Pavel Soucek, Juozas Kupcinskas, Ludmila Vodickova, Daniela Basso, Maarten F. Bijlsma, William Greenhalf, Francesca Tavano, and Verena Katzke
Subjects: Oncology, medicine.medical_specialty, Pancreatic disease, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Gastroenterology, Cancer, Single-nucleotide polymorphism, medicine.disease, Telomere, Continuous variable, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Pancreatic cancer, Mendelian randomization, medicine, SNP, 030211 gastroenterology & hepatology, business
Abstract: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54x10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87x10-6 , ptrend = 3.27x10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98x10-9 for highest vs. lowest quintile; p = 1.82x10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. This article is protected by copyright. All rights reserved.
Published: 2018
Full Text: View/download PDF

13. Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms

Author: Renata Talar-Wojnarowska, Claudio Pasquali, Daniele Campa, Maria Rinzivillo, Valbona Liço, Cinzia Cantù, Federico Canzian, Rita T. Lawlor, Thilo Hackert, Gabriele Capurso, Oliver Strobel, Maria Gazouli, Krzysztof Jamroziak, Antonio De Bonis, Ewa Małecka-Panas, Angelo Andriulli, Livia Archibugi, Paola Fogar, Niccola Funel, Anna Caterina Milanetto, Christos Dervenis, William Greenhalf, Francesca Tavano, Stefano Landi, John P. Neoptolemos, Daniela Basso, Ofure Obazee, Luca Landoni, Carlo Federico Zambon, and Timothy J. Key
Subjects: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, age of onset genes genetic predisposition to disease pancreatic diseases pancreatic neoplasm single nucleotide polymorphism research whites genetics neoplasms islet cell tumor pancreatic adenocarcinoma stratification pancreatic ductal adenocarcinoma false-positive results genome-wide association study causality neoplasm grading, Pancreatic disease, Genotype, PANDoRA consortium, PDAC, genetic susceptibility, pNEN, Single-nucleotide polymorphism, Genome-wide association study, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, Biomarkers, Tumor, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Aged, business.industry, Genetic variants, Case-control study, General Medicine, Middle Aged, medicine.disease, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Adenocarcinoma, Female, Carcinogenesis, Pancreas, business, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study
Abstract: Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.
Published: 2018

14. A multifactorial score for pancreatic ductal adenocarcinoma risk prediction

Author: Manuel Gentiluomo, Alice Alessandra Galeotti, Cosmeri Rizzato, Ofure Obazee, John P. Neoptolemos, Claudio Pasquali, Michael Nentwich, Giulia Martina Cavestro, Raffaele Pezzilli, William Greenhalf, Bernd Holleczek, Cornelia Schroeder, Ben Schöttker, Audrius Ivanauskas, Laura Ginocchi, Timothy J. Key, Péter Hegyi, Livia Archibugi, Erika Darvasi, Daniela Basso, Cosimo Sperti, Maarten F. Bijlsma, Orazio Palmieri, Viktor Hlavac, Renata Talar-Wojnarowska, Beatrice Mohelnikova-Duchonova, Thilo Hackert, Yogesh Vashist, Ondrej Strouhal, Hanneke van Laarhoven, Francesca Tavano, Martin Lovecek, Christos Dervenis, Ferenc Izbéki, Andrea Padoan, Ewa Małecka-Panas, Evaristo Maiello, Giuseppe Vanella, Gabriele Capurso, Jakob R. Izbicki, George E. Theodoropoulos, Krzysztof Jamroziak, Verena Katzke, Rudolf Kaaks, Andrea Mambrini, Ioannis S. Papanikolaou, Richárd Szmola, Andrea Szentesi, Juozas Kupcinskas, Simona Bursi, Eithne Costello, Ugo Boggi, Anna Caterina Milanetto, Stefano Landi, Maria Gazouli, Ludmila Vodickova, Pavel Soucek, Domenica Gioffreda, Federica Gemignani, Hermann Brenner, Oliver Strobel, Markus W. Büchler, Pavel Vodicka, Salvatore Paiella, Federico Canzian, and Daniele Campa
Subjects: Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Published: 2019
Full Text: View/download PDF

15. A Mendelian randomization analysis of known and putative risk factors for pancreatic cancer

Author: Ye Lu, Manuel Gentiluomo, Luca Morelli, Ofure Obazee, Federico Canzian, and Daniele Campa
Subjects: Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Published: 2019
Full Text: View/download PDF

16. Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: a PANDoRA study

Author: Maria Gazouli, Rita T. Lawlor, Ugo Boggi, Jakob R. Izbicki, Raffaelle Pezzilli, Beatrice Mohelnikova-Duchonova, Claudio Pasquali, Rudolf Kaaks, Juozas Kupcinskas, Thilo Hackert, Andrea Mambrini, Giulia Martina Cavestro, Elżbieta Iskierka-Jażdżewska, Hermann Brenner, Angelo Adriulli, Ewa Małecka-Panas, Ofure Obazee, Federico Canzian, Pavel Vodicka, Daniele Campa, Pavel Soucek, and Gabriele Carpurso
Subjects: Oncology, medicine.medical_specialty, Pathology, Pancreatic ductal adenocarcinoma, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Gastroenterology, medicine, business
Published: 2017

17. Abstract 1580: Genetic variability of H3K27me modifier genesEZH2,KDM6AandKDM6Bin association with pancreatic cancer risk

Author: Ye Lu, Ofure Obazee, and Federico Canzian
Subjects: Cancer Research, Oncology
Abstract: Background: Several literature reports explain the critical role of epigenetic regulation in relation to different types of cancers, however this is still an emerging research area in pancreatic cancer. Methylation of lysine 27 on histone H3 (H3K27me) plays a critical role in regulating gene expression and this modification has been reported to have oncogenic effects. Specifically, in pancreatic cancer this mechanism has only been demonstrated in relation to patient outcome. The demethylase KDM6A (UTX) or KDM6B (JMJD3, a paralog of KDM6A on a different chromosome), and methyltransferase EZH2 (KMT6A) specifically regulate the alteration level of H3K27me. Based on the hypothesis that genetic variants may influence overall gene function, it is plausible that single nucleotide polymorphisms (SNPs) in these genes may similarly affect the roles of these genes in H3K27me deregulation. Materials and methods: Using the SNPinfo tool, a total of 21 tag SNPs in EZH2, KDM6A and KDM6B were selected from European populations based on 1000 Genome project. SNPs below 80% linkage disequilibrium threshold or less than 5% frequency among Europeans were excluded. These SNPs were analysed in relation to pancreatic cancer susceptibility using logistic regression among up to 8,741 pancreatic cancer cases and 6,957 controls from publically-available GWAS data (Pancreatic Cancer Cohort Consortium (PanScan) and Pancreatic Cancer Case-Control Consortium (PanC4)). Imputation of these data sets were performed according to standard protocol and used for subsequent analyses. Results: Following adjustment for age and gender, we observed promising associations between KDM6B rs12453250 C>A and EZH2 rs2888566 T>C ((OR=0.92 95% CI (0.85-0.99), P=0.018) and (OR=1.09 95% CI (1.03-1.17), P=0.007) respectively) and pancreatic cancer risk. Interestingly, rs12453250 results in an amino acid change from Phenylalanine (F) to Leucine (L) which is predicted to have a probably-damaging effect on the KDM6B protein. Conclusions: The extent to which epigenetic markers can be incorporated into pancreatic cancer risk prediction along with genetic information is unknown. Our novel findings suggest a plausible role of EZH2 and KDM6A SNPs in relation to pancreatic cancer risk among carriers of their minor alleles. These results warrant further validation in independent studies and may enhance systematic risk assessment among Europeans. Citation Format: Ye Lu, Ofure Obazee, Federico Canzian. Genetic variability of H3K27me modifier genesEZH2,KDM6AandKDM6Bin association with pancreatic cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1580.
Published: 2019
Full Text: View/download PDF

18. Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant

Author: Sylvia Rabstein, Anja Rudolph, Beate Pesch, Gianluca Severi, Anne Lotz, Hiltrud Brauch, Thomas Brüning, Jingmei Li, Laura Baglietto, Dieter Flesch-Janys, Keith Humphreys, Volker Harth, Melissa C. Southey, Ofure Obazee, Jenny Chang-Claude, Ute Hamann, Ulf Hannelius, Per Hall, Christina Justenhoven, Petra Seibold, Christian Baisch, Graham G. Giles, Stefan Winter, and Yon-Dschun Ko
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Heterozygote, Genome-wide association study, Estrone, Breast Neoplasms, Polymorphism, Single Nucleotide, HSD17B1, Estradiol Dehydrogenases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Gene Frequency, Risk Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, Allele, Allele frequency, 030304 developmental biology, 0303 health sciences, business.industry, Medicine (all), Haplotype, Estrogen Replacement Therapy, Case-control study, Single Nucleotide, medicine.disease, 3. Good health, Postmenopause, Breast cancer risk, Hormone replacement therapy, Case-Control Studies, Female, Endocrinology, chemistry, 030220 oncology & carcinogenesis, business
Abstract: 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) plays an important role in the biosynthesis of 17β-estradiol. The current study aimed at confirming the reduced risk of breast cancer in carriers of the non-synonymous HSD17B1_937_A>G (rs605059) polymorphism who used any hormone replacement therapy (HRT) for 10 years or longer. We performed an independent association study using four breast cancer case-control studies from Australia, Germany, and Sweden. In all, 5,777 cases and 8,189 age-matched controls of European descent were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and TaqMan. Risk estimates were calculated by interaction analysis and main effect analysis adjusted for age and study. Main effect analyses for women using any HRT for 10 years or longer (1,428 cases versus 1,724 controls) revealed a protective effect of the HSD17B1_937_G allele on breast cancer risk (OR 0.86, 95 % CI: 0.73-0.99; p = 0.048). Thus, our previous finding of a protective effect of the HSD17B1_937_G allele on HRT-associated breast cancer risk has now been confirmed both in independent large patient cohorts and a comprehensive pooled analysis supporting the hypothesis that a HSD17B1-mediated decreased conversion of estrone to the more potent 17β-estradiol may reduce the estrogenic effects, thereby reducing the risk of developing breast cancer during long-term HRT use.
Published: 2013
Full Text: View/download PDF

19. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: Anne Tjønneland, Jason W. Hoskins, Kala Visvanathan, Yogesh K. Vashist, Dimitrios Trichopoulos, Matthew H. Kulke, Ruth C. Travis, Charles S. Fuchs, Herbert Yu, Kai Yu, Phyllis J. Goodman, Michael Goggins, Jean Wactawski-Wende, Laurie Burdette, Joanne W. Elena, Andrea Mambrini, Petra H.M. Peeters, H. Bas Bueno-de-Mesquita, Maria Teresa Landi, Ulrike Peters, Mingfeng Zhang, Laurence N. Kolonel, Hermann Brenner, Elżbieta Iskierka-Jażdżewska, Robert C. Kurtz, Stephen J. Chanock, Marie-Christine Boutron-Ruault, Ann L. Oberg, Elio Riboli, Maarten F. Bijlsma, Eric J. Jacobs, Manolis Kogevinas, Evelina Mocci, Steven Gallinger, Jinping Jia, Mark P. Purdue, Raffaele Pezzilli, Harvey A. Risch, Demetrius Albanes, Irene Collins, Maria Gazouli, Michelle Cotterchio, Oliver Strobel, Erica J. Childs, Charles C. Chung, Geoffrey S. Tobias, J. Ramón Quirós, Núria Malats, Robert N. Hoover, Pavel Vodicka, Brian M. Wolpin, Ugo Boggi, Patricia Hartge, Gloria M. Petersen, Peter Kraft, Christopher Hautman, Gary E. Goodman, Manal Hassan, Donghui Li, Howard D. Sesso, Malin Sund, Julie E. Buring, Loic Le Marchand, Wei Zheng, Xiao-Ou Shu, Ewa Małecka-Panas, Pavel Soucek, Salvatore Panico, Nicolas Wentzensen, Graham G. Giles, Alpa V. Patel, Daniele Campa, Myron D. Gross, Ghislaine Scelo, J. Michael Gaziano, Juozas Kupcinskas, Debra T. Silverman, Laufey T. Amundadottir, Rachael S. Stolzenberg-Solomon, Neil E. Caporaso, Mazda Jenab, Sara H. Olson, Stefano Landi, Giulia Martina Cavestro, Aruna Kamineni, Laura Beane-Freeman, Roger L. Milne, Rachel E. Neale, Aldo Scarpa, Kathy J. Helzlsouer, Miquel Porta, Emily White, Eric J. Duell, Paige M. Bracci, Nan Hu, Federico Canzian, Eric A. Klein, Gabriele Capurso, Anne Zeleniuch-Jacquotte, Eithne Costello, David J. Hunter, Rudolf Kaaks, Sonja I. Berndt, Kay-Tee Khaw, Nathaniel Rothman, Christian C. Abnet, Francesca Tavano, Christopher A. Haiman, Zhaoming Wang, Ofure Obazee, Alan A. Arslan, Edward Giovannucci, Alison P. Klein, Daniela Basso, Charles Kooperberg, Philip R. Taylor, Satu Männistö, Timothy J. Key, Mark D. Thornquist, Gabriella Andreotti, Lauren K. Brais, Gisella Figlioli, Vittorio Krogh, University Medical Center Utrecht, Imperial College Trust, Cancer Research UK, Medical Research Council UK (MRC), National Institute for Health Research (NIHR), Cancer Research UK (Reino Unido), Medical Research Council (Reino Unido), National Institute for Health Research (Reino Unido), Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetriu, Andreotti, Gabriella, Brais, Lauren, Bueno de Mesquita, H. Ba, Basso, Daniela, Berndt, Sonja I, Boutron Ruault, Marie Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Klein, Eric A, Kogevinas, Manoli, Krogh, Vittorio, Kupcinskas, Juoza, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H. M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J. Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrio, Vashist, Yogesh, Vodicka, Pavel, Wactawski Wende, Jean, Wentzensen, Nicola, Yu, Herbert, Yu, Kai, Zeleniuch Jacquotte, Anne, Kooperberg, Charle, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charle, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T., Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, Ej, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, Cc, Hautman, C, Arslan, Aa, Beane Freeman, L, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Giles, Gg, Goodman, Ge, Goodman, Pj, Kamineni, A, Kolonel, Ln, Kulke, Mh, Malats, N, Olson, Sh, Sesso, Hd, Visvanathan, K, White, E, Zheng, W, Abnet, Cc, Albanes, D, Andreotti, G, Brais, L, Bueno de Mesquita, Hb, Basso, D, Berndt, Si, Boutron Ruault, Mc, Bijlsma, Mf, Brenner, H, Burdette, L, Campa, D, Caporaso, Ne, Capurso, G, Cavestro, GIULIA MARTINA, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, Jm, Gazouli, M, Giovannucci, El, Goggins, M, Gross, M, Haiman, Ca, Hassan, M, Helzlsouer, Kj, Hu, N, Hunter, Dj, Iskierka Jazdzewska, E, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Klein, Ea, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, Rc, Landi, Mt, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, Rl, Neale, Re, Oberg, Al, Panico, S, Patel, Av, Peeters, Ph, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Quiros, Jr, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, Xo, Silverman, Dt, Soucek, P, Strobel, O, Sund, M, Małecka Panas, E, Taylor, Pr, Tavano, F, Travis, Rc, Thornquist, M, Tjønneland, A, Tobias, G, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Kooperberg, C, Risch, Ha, Jacobs, Ej, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, Sj, Petersen, Gm, Stolzenberg Solomon, R, Wolpin, Bm, Kraft, P, Klein, Ap, Canzian, F, and Amundadottir, L. T.
Subjects: 0301 basic medicine, Candidate gene, Pancreatic disease, GENETIC SUSCEPTIBILITY, pancreatic cancer, Datasets as Topic, Genome-wide association study, imputation, TRET, 0302 clinical medicine, Fine-mapping, GWAS, Imputation, NR5A2, Pancreatic cancer, Oncology, Genotype, Genetics, 3. Good health, fine-mapping, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 8, 616.37-006.6 [udc], BLADDER-CANCER, Single-nucleotide polymorphism, GENOTYPE IMPUTATION, BREAST, Polymorphism, Single Nucleotide, 03 medical and health sciences, Journal Article, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Pàncrees -- Càncer, Cancer och onkologi, LONG-RANGE INTERACTION, business.industry, medicine.disease, Pancreatic neoplasms, genetics, Polymorphism, single nucleotide, RISK LOCI, Fold change, COMMON VARIANT, Cromosomes, Pancreatic Neoplasms, 030104 developmental biology, Cancer and Oncology, business, Imputation (genetics), LRH-1, Priority Research Paper, Genome-Wide Association Study
Abstract: Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials. Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10 −15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10 −9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10 −4 -2.0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
Published: 2016

20. Genetic variability of the ABCC2 gene and overall survival in pancreatic cancer

Author: Jakob R. Izbicki, William Greenhalf, Manuel Gentiluomo, Gabriele Capurso, Markus W. Büchler, Paula Puchalt García, Giulia Martina Cavestro, Federico Canzian, Beatrice Mohelnikova-Duchonova, Martin Lovecek, Péter Hegyi, Ewa Małecka-Panas, Yogesh K. Vashist, John P. Neoptolemos, Angelo Andriulli, Alice Alessandra Galeotti, Claudio Pasquali, Juozas Kupcinskas, Pavel Soucek, Andrea Mambrini, Daniele Campa, Raffaele Pezzilli, Aldo Scarpa, Ugo Boggi, Olivier R. Busch, and Ofure Obazee
Subjects: Oncology, medicine.medical_specialty, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, Gastroenterology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, ABCC2 Gene, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, medicine, Overall survival, 030211 gastroenterology & hepatology, Genetic variability, business
Published: 2018
Full Text: View/download PDF

21. Novel pancreatic cancer susceptibility loci discovered through genome-wide association studies

Author: Federico Canzian, Daniele Campa, Ofure Obazee, Cosmeri Rizzato, Maria Gazouli, Giulia Martina Cavestro, Aldo Scarpa, Stefania Moz, Raffaele Pezzilli, Andrea Mambrini, Ugo Boggi, Gabriele Capurso, Livia Archibugi, Franco Bambi, Angelo Andriulli, Pavel Soucek, Pavel Vodicka, Beatrice Mohelnikova-Duchonova, Martin Lovecek, Thilo Hackert, John P. Neoptolemos, Oliver Strobel, Yogesh K. Vashist, Jakob R. Izbicki, Rudolf Kaaks, Hermann Brenner, Peter Hegyi, Olivier Busch, H. Bas Bueno-de-Mesquita, Petra H.M. Peeters, Ewa Malecka-Panas, Krzysztof Jamroziak, Juozas Kupcinskas, Eithne Costello, Kay-Tee Khaw, Timothy J. Key, Rachael Stolzenberg-Solomon, Brian Wolpin, Alison P. Klein, and Laufey T. Amundadottir
Subjects: Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Published: 2018
Full Text: View/download PDF

22. The PANcreatic DISEASE ReseArch (PANDoRA) consortium: an update

Author: Federico Canzian, Ofure Obazee, Thilo Hackert, John P. Neoptolemos, Oliver Strobel, Yogesh K. Vashist, Jakob R. Izbicki, Rudolf Kaaks, Hermann Brenner, Peter Hegyi, Ugo Boggi, Luca Morelli, Franco Bambi, Gabriele Capurso, Raffaele Pezzilli, Andrea Mambrini, Cosimo Sperti, Aldo Scarpa, Angelo Andriulli, Giulia Martina Cavestro, Paolo G. Arcidiacono, Alessandro Zerbi, William Greenhalf, Timothy J. Key, Kay-Tee Khaw, Pavel Vodicka, Pavel Soucek, Beatrice Mohelnikova-Duchonova, Martin Lovecek, Ewa Malecka-Panas, Krzysztof Jamroziak, Juozas Kupcinskas, Maria Gazouli, Olivier Busch, Casper H.J. van Eijck, H. Bas Bueno-de-Mesquita, Petra H.M. Peeters, Julia S. Johansen, Natalya Gubergrits, Keitaro Matsuo, Shogo Kikuchi, and Daniele Campa
Subjects: Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Published: 2018
Full Text: View/download PDF

23. Abstract 3411: Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: a PANDoRA study

Author: Jakob R. Izbicki, Hermann Brenner, Elżbieta Iskierka-Jażdżewska, Rudolf Kaaks, Federico Canzian, Pavel Soucek, Juozas Kupcinskas, Gabriele Capurso, Andrea Mambrini, Daniele Campa, Giulia Martina Cavestro, Thilo Hackert, Beatrice Mohelnikova Duchonova, Maria Gazouli, Ewa Małecka Panas, Aldo Scarpa, Raffaele Pezzilli, Claudio Pasquali, Pavel Vodicka, Ugo Boggi, Angelo Andriulli, and Ofure Obazee
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Pathology, Pancreatic ductal adenocarcinoma, business.industry, Internal medicine, medicine, business
Abstract: Background: The incredibly poor outlook of pancreatic cancer patients underscores an urgent need for early diagnostic markers. Pancreatic cancer ranks third most-frequent among BRCA1/2-deficient cancers with germline mutations detected in T) which introduces a premature stop codon thus truncating the protein, has previously been implicated in familial PDAC, but not in sporadic cases. A frameshift pathogenic mutation c.6503delTT (rs11571658, p.Leu2092Profs) reported to occur in tandem with K3326X in breast and ovarian cancer families, has also been speculated to influence risk associations due to linkage disequilibrium between both variants. Method and results: K3326X was genotyped in 2,969 sporadic cases and 4,700 controls using Taqman chemistry and fidelity of genotypes assessed based on concordance of internal replicates and negative controls. K3326X was observed in 1.2% of cases and 0.8% of controls. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated by multivariate unconditional logistic regression with adjustment for age, sex and region of origin. We also performed a stratified analysis based on age at diagnosis to estimate the risk association between K3326X and early-onset pancreatic cancer. To rule out the likely shared effect of the c.6503delTT mutation on sporadic PDAC risk, we also sequenced DNA from carriers of K3326X in this study. We found K3326X to be associated with increased risk of developing sporadic PDAC ((OR = 1.71, 95% CI = 1.18 - 2.49), P = 0.005). This risk was considerably higher among cases aged 50 years and younger (OR = 2.13, 95% CI = 1.10 - 4.11, P = 0.03). Furthermore, carriers of K3326X did not bear the c.6503delTT mutation thus confirming that the observed risk effect was not influenced by the latter. Conclusion: These robust associations implicate K3326X in the etiology of sporadic and early-onset PDAC, and therefore warrant replication as well as functional studies to elucidate the role of K3326X in DNA repair mechanisms. Citation Format: Ofure M. Obazee, Gabriele Capurso, Angelo Andriulli, Pavel Soucek, Ewa Małecka- Panas, Juozas Kupcinskas, Rudolf Kaaks, Maria Gazouli, Thilo Hackert, Aldo Scarpa, Giulia M. Cavestro, Claudio Pasquali, Hermann Brenner, Daniele Campa, Raffaele Pezzilli, Andrea Mambrini, Beatrice Mohelnikova- Duchonova, Ugo Boggi, Jakob Izbicki, Pavel Vodicka, Elzbieta Iskierka-Jazdzewska, Federico Canzian. Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: a PANDoRA study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3411. doi:10.1158/1538-7445.AM2017-3411
Published: 2017
Full Text: View/download PDF

24. Do pancreatic adenocarcinomas and neuroendocrine neoplasms share genetic susceptibility a PANDoRA study

Author: Ugo Boggi, Oliver Strobel, Kay-Tee Khaw, Aldo Scarpa, Gabriele Capurso, John P. Neoptolemos, Claudio Pasquali, Angelo Andriulli, Daniele Campa, Stefano Landi, Ewa Małecka-Panas, Timothy J. Key, Federico Canzian, Ofure Obazee, Rudolf Kaaks, and Maria Gazouli
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Hepatology, business.industry, 030220 oncology & carcinogenesis, Endocrinology, Diabetes and Metabolism, Gastroenterology, Genetic predisposition, Cancer research, Medicine, business
Published: 2017
Full Text: View/download PDF

25. The UGT1A6_19_GG genotype is a breast cancer risk factor

Author: Dieter Flesch-Janys, Volker Harth, Anja Rudolph, Vesa Kataja, Arto Mannermaa, Mervi Grip, Beate Pesch, Sylvia Rabstein, Robert Winqvist, Per Hall, Katri Pylkäs, Ute Hamann, Ofure Obazee, Veli-Matti Kosma, Petra Seibold, Jingmei Li, Arif B. Ekici, Thomas Brüning, Hiltrud Brauch, Christina Justenhoven, Matthias Beckmann, Anne Lotz, Arja Jukkola-Vuorinen, Peter A. Fasching, Jenny Chang-Claude, Jaana M. Hartikainen, Stefan Winter, Yon-Dschun Ko, Alexander Hein, and Christian Baisch
Subjects: Oncology, medicine.medical_specialty, lcsh:QH426-470, Population, Logistic regression, polymorphism, 03 medical and health sciences, breast cancer risk, 0302 clinical medicine, Breast Cancer Risk Factor, Breast cancer, Medizinische Fakultät, Polymorphism (computer science), Internal medicine, Genotype, Genetics, Medicine, Original Research Article, ddc:610, education, Genotyping, Genetics (clinical), 030304 developmental biology, Pharmacology, validation, 0303 health sciences, education.field_of_study, business.industry, medicine.disease, 3. Good health, lcsh:Genetics, Pooled analysis, 030220 oncology & carcinogenesis, Molecular Medicine, business, metabolism, UGT1A6
Abstract: Validation of an association between the UGT1A6_19_TG (rs6759892) polymorphism and overall breast cancer risk. A pilot study included two population-based case-control studies from Germany (MARIE-GENICA). An independent validation study comprised four independent breast cancer case-control studies from Finland (KBCP, OBCS), Germany (BBCC), and Sweden (SASBAC). The pooled analysis included 7418 cases and 8720 controls from all six studies. Participants were of European descent. Genotyping was done by MALDI-TOF MS and statistical analysis was performed by logistic regression adjusted for age and study. The increased overall breast cancer risk for women with the UGT1A6_19_GG genotype which was observed in the pilot study was confirmed in the set of four independent study collections (OR 1.13, 95% CI 1.05-1.22; p = 0.001). The pooled study showed a similar effect (OR 1.09, 95% CI 1.04-1.14; p = 0.001). The risk effect on the basis of allele frequencies was highly significant, the pooled analysis showed an OR of 1.11 (95% CI 1.06-1.16; p = 5.8 × 10(-6)). We confirmed the association of UGT1A6_19_GG with increased overall breast cancer risk and conclude that our result from a well powered multi-stage study adds a novel candidate to the panel of validated breast cancer susceptibility loci.
Published: 2013
Full Text: View/download PDF

26. The pharmacogenomics of sex hormone metabolism: breast cancer risk in menopausal hormone therapy

Author: Ofure Obazee, Christina Justenhoven, and Hiltrud Brauch
Subjects: medicine.medical_specialty, Neoplasms, Hormone-Dependent, medicine.medical_treatment, Breast Neoplasms, Bioinformatics, Breast cancer, Sex hormone-binding globulin, Risk Factors, Internal medicine, Genetics, medicine, Humans, Precision Medicine, Adverse effect, Gonadal Steroid Hormones, Pharmacology, Polymorphism, Genetic, biology, business.industry, Estrogen Replacement Therapy, medicine.disease, Menopause, Endocrinology, Treatment Outcome, Transgender hormone therapy, Pharmacogenomics, biology.protein, Molecular Medicine, Female, Hormone therapy, business, Hormone
Abstract: With women in western countries spending nearly one-third of their lifetime beyond menopause and a substantial number of these women facing severe menopausal symptoms, the goal of sex hormone pharmacogenomics is to promote the safe use of hormone replacement therapy (HRT). This could be achieved by providing molecular predictors for the upfront stratification of women in need of relief from menopausal symptoms into those with a likely benefit from HRT and those with a contraindication due to an HRT-associated breast cancer risk or other adverse effects. An increasing knowledge base of sex hormone metabolism and its variability, HRT outcomes and breast cancer susceptibility, as well as emerging examples of pharmacogenomic predictors, underscore the potential relevance of genetic variations for HRT outcome. The genes responsible for the metabolism, signaling and action of sex hormones are at the heart of this research; however, pharmacogenomic investigation of their therapeutic effects due to the enormous complexity of the biological pathways involved is still in its infancy. This article discusses the current knowledge, challenges and potential future directions towards the goal of genotype-guided safer HRT use.
Published: 2012

27. The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant

Author: Ulf Hannelius, Gianluca Severi, Per Hall, Keith Humphreys, Janet E. Olson, Peter A. Fasching, Matthias W. Beckmann, Jingmei Li, Christian Baisch, Laura Baglietto, Christina Justenhoven, Thomas Brüning, Hiltrud Brauch, Ofure Obazee, Volker Harth, Fergus J. Couch, Ute Hamann, Melissa C. Southey, Arif B. Ekici, Stefan Winter, Anne Lotz, Graham G. Giles, Sylvia Rabstein, Yon Ko, and Beate Pesch
Subjects: Risk, Cancer Research, Extramural, Medicine (all), media_common.quotation_subject, Estrogen Replacement Therapy, Genetic variants, Breast Neoplasms, Art, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP2C19, Female, Gonadal Steroid Hormones, Humans, Postmenopause, Oncology, Postmenopausal Hormone Replacement Therapy, Estrogen plus progestin, Religious studies, Estrogen replacement therapy, media_common
Abstract: Christina Justenhoven • Ofure Obazee • Stefan Winter • Fergus J. Couch • Janet E. Olson • Per Hall • Ulf Hannelius • Jingmei Li • Keith Humphreys • Gianluca Severi • Graham Giles • Melissa Southey • Laura Baglietto • Peter A. Fasching • Matthias W. Beckmann • Arif B. Ekici • Ute Hamann • Christian Baisch • Volker Harth • Sylvia Rabstein • Anne Lotz • Beate Pesch • Thomas Bruning • Yon-Dschun Ko • Hiltrud Brauch
Published: 2011

28. Abstract 1337: The UGT1A6_19_GG genotype is associated with increased breast cancer risk based on a two-stage study

Author: Ute Hamann, Sylvia Rabstein, Volker Harth, Per Hall, Thomas Brüning, Robert Winqvist, Christina Justenhoven, Hiltrud Brauch, Anne Lotz, Arto Mannermaa, Beate Pesch, Peter A. Fasching, Jenny Chang-Claude, Stefan Winter, Jaana M. Hartikainen, Yon-Dschun Ko, Christian Baisch, and Ofure Obazee
Subjects: Oncology, Cancer Research, medicine.medical_specialty, education.field_of_study, business.industry, Population, Cancer, Genome-wide association study, medicine.disease, Bioinformatics, Breast cancer, Polymorphism (computer science), Internal medicine, Genotype, medicine, business, education, Carcinogen, Genetic association
Abstract: Over 20 breast cancer susceptibility loci have been identified mainly by genome-wide association studies (GWAS). These include Fibroblast Growth Factor Receptor (FGFR2) and loci close to the cell cycle regulator Cyclin D1 (CCND1) at 11q13. Phase I and II enzymes are anticipated to also contribute to breast cancer risk due to their roles in the inactivation, detoxification and elimination of endogenous and exogenous carcinogenic compounds. However, a GWAS approach is inappropriate for many genes due to their high degree of sequence homologies. For the UDP glucuronosyltransferase 1 family, polypeptide A6 (UGT1A6), a key player in Phase II steroid metabolism, we pursued a candidate approach using a specific assay design for gene amplification. We focused on the UGT1A6_19_T>G polymorphism (rs6759892) because this variant has been suggested to decrease enzyme activity. Moreover, our prior efforts showed an association between the UGT1A6_19_GG genotype and increased breast cancer risk (OR 1.17; 95% CI: 1.03-1.34; p = 0.014) in two population-based breast cancer case-control studies from Germany (3,139 cases and 5,466 controls) (MARIE-GENICA, 2010, Breast Cancer Res Treat 119:463-74). To validate these findings we extended the analysis to four independent study collections from Finland (KBCP, OBCS), Germany (BBCC) and Sweden (SASBAC) comprising 3,635 cases and 2,648 controls. Moreover, we performed a pooled analysis of all study subjects (7,418 cases and 8,720 controls) all being of European descent. UGT1A6_19_T>G genotyping was done by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and statistical analysis by logistic regression adjusted for age and study using SPSS. Power calculation was done with nQuery Advisor ® which showed that the pooled study had an 80% power to detect a minimum OR of 1.06 (α = 0.05, two-sided test). The analysis of the BBCC, KBCP, OBCS and SASBAC collections confirmed our previous findings showing an increased overall breast cancer risk among women with the UGT1A6_19_GG genotype (OR 1.13; 95% CI: 1.05-1.22; p = 0.001). The pooled study showed a similar effect (OR 1.09; 95% CI: 1.04-1.14; p = 0.0004). We conclude based on the significant association between the UGT1A6_19_GG variant and breast cancer that a decreased conjugation activity of UGT1A6 might elevate the exposure to carcinogenic compounds thereby increasing the risk of breast cancer. Citation Format: Ofure M. Obazee, Christina Justenhoven, Stefan Winter, Sylvia Rabstein, Anne Lotz, Volker Harth, Beate Pesch, Thomas Brüning, Christian Baisch, Jaana M. Hartikainen, Arto Mannermaa, Robert Winqvist, Peter Fasching, Per Hall, Jenny Chang-Claude, Ute Hamann, Yon-Dschun Ko, Hiltrud Brauch. The UGT1A6_19_GG genotype is associated with increased breast cancer risk based on a two-stage study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1337. doi:10.1158/1538-7445.AM2013-1337
Published: 2013
Full Text: View/download PDF

29. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: Christopher A. Haiman, Herbert Yu, Lauren K. Brais, Gabriele Capurso, Eric J. Duell, Michelle Cotterchio, Núria Malats, Beatrice Mohelníková-Duchoňová, Claudio Pasquali, Gary E. Goodman, Giulia Martina Cavestro, Kala Visvanathan, Sean P. Cleary, Jill P. Smith, Jean Wactawski-Wende, Rita T. Lawlor, Gianluca Severi, J. Michael Gaziano, Kathy J. Helzlsouer, Charles C. Chung, Harvey A. Risch, Stephen K. Van Den Eeden, Elizabeth A. Holly, Bas Bueno-de-Mesquita, Patricia Hartge, Fei Chen, Mark D. Thornquist, Hermann Brenner, Ulrike Peters, Ghislaine Scelo, Steven Gallinger, Sonja I. Berndt, Howard D. Sesso, Lenka Foretova, Laufey T. Amundadottir, Mingfeng Zhang, Federico Canzian, Rudolf Kaaks, Stephen J. Chanock, Nicolas Wentzensen, Ann L. Oberg, Eric J. Jacobs, Peter Kraft, Rayjean J. Hung, Evelina Mocci, Maria Gazouli, Francesca Tavano, Michael Borges, Zhaoming Wang, Alan A. Arslan, Wei Zheng, Ayelet Borgida, Paige M. Bracci, Jason W. Hoskins, William R. Bamlet, Juozas Kupcinskas, Joseph M. Herman, Demetrius Albanes, Charles S. Fuchs, Nathaniel Rothman, Niccola Funel, Pavel Soucek, Edward Giovannucci, Paul Brennan, Thilo Hackert, Jun Zhong, Manolis Kogevinas, Robert N. Hoover, Michael Goggins, Amanda L. Blackford, Robert J. Kurtz, Malin Sund, Roger L. Milne, Stefano Landi, Francisco X. Real, Emily White, Miquel Porta, Ivana Holcatova, Kari G. Chaffee, Vladimir Janout, Charles Kooperberg, Péter Hegyi, Frederike Dijk, Yogesh K. Vashist, Andrea Mambrini, Matthew H. Kulke, I. Min Lee, Kai Yu, Alison P. Klein, Phyllis J. Goodman, Donghui Li, Julie E. Buring, Debra T. Silverman, Ana Babic, John P. Neoptolemos, Erica J. Childs, Alpa V. Patel, Sara H. Olson, Brian M. Wolpin, Krzysztof Jamroziak, Gloria M. Petersen, Xiao-Ou Shu, Renata Talar-Wojnarowska, Rachel E. Neale, Daniel A. Laheru, Kay-Tee Khaw, Eric A. Klein, Ashley Jermusyk, Graham G. Giles, Daniele Campa, Laura Beane-Freeman, Rachael Z. Stolzenberg-Solomon, Raffaele Pezzilli, Geoffrey S. Tobias, Pavel Vodicka, Irene Orlow, Anne Zeleniuch-Jacquotte, Ofure Obazee, Satu Männistö, Lingeng Lu, Manal Hasan, Loic LeMarchand, Gabriella Andreotti, CCA - Cancer biology and immunology, Pathology, Lung Cancer Research Foundation, Sol Goldman Pancreas Cancer Research Center, Geoffrey Beene Foundation, Arnold and Arlene Goldstein Family Foundation, National Health and Medical Research Council (Australia), Czech Science Foundation, Joan Rombauer Pancreatic Cancer Foundation, NIH - National Cancer Institute (NCI) (Estados Unidos), Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología (España), Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública), Mocci, Evelina [0000-0002-7101-9556], Canzian, Federico [0000-0002-4261-4583], Chaffee, Kari G [0000-0002-7313-1875], Dijk, Frederike [0000-0003-3970-6601], Gazouli, Maria [0000-0002-3295-6811], Jacobs, Eric J [0000-0002-8458-7659], Klein, Eric A [0000-0002-1783-0698], Lu, Lingeng [0000-0001-9871-0809], Malats, Núria [0000-0003-2538-3784], Milne, Roger L [0000-0001-5764-7268], Neoptolemos, John P [0000-0002-6201-7399], Oberg, Ann L [0000-0003-2539-9807], Pezzilli, Raffaele [0000-0001-9827-7451], Porta, Miquel [0000-0003-1684-7428], Real, Francisco X [0000-0001-9501-498X], Sund, Malin [0000-0002-7516-9543], Tobias, Geoffrey S [0000-0002-2878-8253], Van Den Eeden, Stephen K [0000-0002-5599-8387], Yu, Herbert [0000-0003-3950-4815], Zheng, Wei [0000-0003-1226-070X], Obazee, Ofure [0000-0001-8791-5008], Amundadottir, Laufey T [0000-0003-1859-8971], Apollo - University of Cambridge Repository, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetriu, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Ba, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charle, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manoli, Kooperberg, Charle, Kulke, Matthew H., Kupcinskas, Juoza, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicola, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.
Subjects: 0301 basic medicine, Oncology, Genetics and Molecular Biology (all), Pancreatic disease, Chemistry(all), General Physics and Astronomy, Genome-wide association study, Disease, Biochemistry, DISEASE, Tensins, Databases, Genetic, IMPUTATION, 03.02. Klinikai orvostan, lcsh:Science, Càncer, Pancreas cancer, GENE-EXPRESSION, Cancer, RISK, Multidisciplinary, Chemistry (all), Pancreatic Neoplasm, Intracellular Signaling Peptides and Proteins, HNF1B, 3. Good health, TRANSCRIPTION FACTORS, Hepatocyte Nuclear Factor 4, Intercellular Signaling Peptides and Proteins, Human, Carcinoma, Pancreatic Ductal, medicine.medical_specialty, Science, Physics and Astronomy(all), Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Physics and Astronomy (all), Cancer epidemiology, Pancreatic cancer, Internal medicine, medicine, Carcinoma, Humans, Genetic Predisposition to Disease, Allele, Càncer de pàncrees, Hepatocyte Nuclear Factor 1-beta, Cancer och onkologi, Biochemistry, Genetics and Molecular Biology (all), business.industry, Biochemistry, Genetics and Molecular Biology(all), Protein, Proteins, ADENOCARCINOMA, General Chemistry, Repressor Protein, medicine.disease, Pancreatic Neoplasms, Repressor Proteins, BODY-MASS INDEX, 030104 developmental biology, Tensin, Cancer and Oncology, Expression quantitative trait loci, lcsh:Q, business, ASSOCIATION ANALYSES, Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10−8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10−14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10−10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10−8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10−8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene., Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

29 results on '"Ofure Obazee"'

1. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

2. Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer

3. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

4. Variations in cag pathogenicity island genes of Helicobacter pylori from Latin American groups may influence neoplastic progression to gastric cancer

5. Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction

6. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

7. Genome-wide association study identifies an early onset pancreatic cancer risk locus

8. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

9. Genetic polymorphisms in the cag pathogenicity island of Helicobacter pylori and risk of stomach cancer and high-grade premalignant gastric lesions

10. Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium

11. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

12. Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study

13. Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms

14. A multifactorial score for pancreatic ductal adenocarcinoma risk prediction

15. A Mendelian randomization analysis of known and putative risk factors for pancreatic cancer

16. Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: a PANDoRA study

17. Abstract 1580: Genetic variability of H3K27me modifier genesEZH2,KDM6AandKDM6Bin association with pancreatic cancer risk

18. Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant

19. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

20. Genetic variability of the ABCC2 gene and overall survival in pancreatic cancer

21. Novel pancreatic cancer susceptibility loci discovered through genome-wide association studies

22. The PANcreatic DISEASE ReseArch (PANDoRA) consortium: an update

23. Abstract 3411: Rare BRCA2 K3326X increases susceptibility to sporadic pancreatic ductal adenocarcinoma: a PANDoRA study

24. Do pancreatic adenocarcinomas and neuroendocrine neoplasms share genetic susceptibility a PANDoRA study

25. The UGT1A6_19_GG genotype is a breast cancer risk factor

26. The pharmacogenomics of sex hormone metabolism: breast cancer risk in menopausal hormone therapy

27. The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant

28. Abstract 1337: The UGT1A6_19_GG genotype is associated with increased breast cancer risk based on a two-stage study

29. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

29 results on '"Ofure Obazee"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources