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Cancer Epidemiology Research Programme ABOUT US T he Catalan Institute of Oncology (ICO) is a public research institute that takes a comprehensive approach towards cancer treatment by focussing on prevention, patient care, specialist training and research. With more than 1000 permanent and temporary staff, ICO’s organisational structure is based on a multicentre, regional model that includes a network of monographic cancer centres–located in Barcelona (L’Hospitalet and Badalona), Girona and Tarragona, as well as several teaching and general hospitals, and research institutes, including the University Hospital of Bellvitge and the Institute of Biomedical Research (IDIBELL). ICO’s mission is to reduce the impact of cancer in Catalonia by bringing the ‘specialist’ to the patient and to ensure the provision of the highest quality health care possible. T he Cancer Epidemiology Research Programme (PREC) at ICO is devoted to research on the causes, epidemiology, early diagnosis and prevention of cancer. PREC provides advice on the design, development and assessment of cancer prevention strategies, such as providing assessments of population-based cancer screening programmes, and providing estimates of costeffectiveness of health promotion programming and cancer prevention measures. With demonstrated expertise in the areas of laboratory, clinical and population-based methods, PREC has become internationally recognised for conducting high quality research, while its scientists have made cutting-edge discoveries and noteworthy contributions to the field of cancer epidemiology. PREC is composed of two units: Infections and Cancer and Nutrition and Cancer. F. Xavier Bosch Silvia de Sanjosé Administration & Management IT Cristina Rajo Jesús Muñoz F. Xavier Bosch Monographs & PVR Journal F. Xavier Bosch Courses & Projects Assumpta Company INCA UNIC UNAC Xavier Castellsagué Antoni Agudo Miguel Angel Pavón Genotyping HPV Information Centre PREDICOP Laia Bruni Antoni Agudo, Genevieve Buckland, Noemie Travier Molecular Epidemiology Gastric Cancer Miguel Angel Pavón Screening and Quality Assurance Laia Alemany Carlos A González, Núria Sala, Antoni Agudo Montserrat Torres Modelling Quality Control Mireia Diaz Pancreatic Cancer Eric J Duell Ana Estaban Vaccines EPIC-Europe Xavier Castellsagué, F. Xavier Bosch, Maria Brotons Inflammation Antoni Agudo, Paula Jakszyn Screening Iron Silvia de Sanjosé Paula Jakszyn Acrylamide Haematoncology Eric J Duell Silvia de Sanjosé, Delphine Casabonne, Laura Costa Polyphenols Raul Zamora INFECTIONS AND CANCER UNIT (UNIC) U NIC places a special emphasis on the accumulation of aetiological knowledge regarding exposure and genetic susceptibility of cancer, and its application to primary prevention. Much of UNIC’s research utilises molecular epidemiology to determine the underlying molecular mechanisms associated with the viral origins of cancer. With collaborations in more than 60 countries, the unit has become a leading authority in the field of viral infections and cancer—with HPV-related research receiving high-priority for the last twenty years. Contact Information: Infections and Cancer Unit (UNIC) Head of Unit: Xavier Castellsagué Email: [email protected] Phone: +34 932 607 812 Website: http://icoepi.net/infections-and-cancer-unit/ HPV-RELATED RESEARCH INFECTIONS AND CANCER LABORATORY (INCA-LAB) P REC’s Infections and Cancer Laboratory (INCA-LAB) is composed of a multidisciplinary team of biologists, virologists, technicians, PhD students and post-docs. The INCA-LAB conducts research focusing on the molecular epidemiology of HPV by supporting national and international epidemiological studies. The techniques applied in the laboratory include commercial and in-house PCR-genotyping in different formats, as well as studies of variants. The INCALAB also conducts validation studies of new technologies for possible application in the field of research and clinical investigation. The INCA-LAB is recognised as a reference laboratory for HPV screening in Catalonia. The lab heads up quality control of HPV performance assays (e.g., inter- and intra-laboratory assessment) as part of the cervical cancer screening activities in Catalonia. In addition, the INCALAB performs detection and genotyping of HPV-DNA as part of the clinical diagnosis process. Contact Information: Infections and Cancer Laboratory (INCA-LAB) Head of Laboratory: Miguel Angel Pavón Email: [email protected] Phone: +34 932 607 812 Website: http://www.idibell.cat/modul/infections-and-cancer-laboratory/en MOLECULAR EPIDEMIOLOGY T he Retrospective International Survey of HPV Time Trends Cervical Cancer (RIS HPV TT) and The International Survey on HPV Prevalence and Type Distribution in Vulvar, Vaginal, Anal, Penile and Oropharyngeal Neoplasias (HPV VVAPO). One of the unit’s primary lines of research includes the study of HPVDNA prevalence and genotype distribution in preneoplastic lesions and cancers of the vulva, vagina, anus, penis, head and neck (namely the RIS HPV TT and the HPV VVAPO studies). The main objectives of these two studies are to: 1) obtain robust prevalence estimates of HPV-attributed preneoplastic lesions and cancer in these anatomical sites, and 2) report the global type distribution of HPV according to geographical area, age and year of diagnosis. The studies involve the participation of more than 90 centres in 45 countries. At present, more than 15 000 samples of cancerous tissue have been collected, preserved in paraffin and analysed. Principal results are now available online and in print. PI: Laia Alemany Key Publication: Alemany L, et al. HPV DNA prevalence and type distribution in anal carcinomas worldwide. Int J Cancer, 2015 Jan 1; 136 (1):98-107. doi: 10.1002/ ijc.28963. Epub 2014 May 30. IF: 5,007; Q1; PMID: 24817381 HPV INFORMATION D issemination of information on HPV and cancer. UNIC has developed and maintains the ICO/IARC Information Centre on HPV and Cancer. The ICO/IARC HPV Information Centre is a web-based resource designed to compile, edit and disseminate scientific data on HPV and HPV-related cancers. The Centre’s mission is to ‘accelerate the development and introduction of HPV prevention strategies to reduce the incidence of cervical cancer and other HPV-related diseases worldwide.’ The Centre provides data and information regarding HPV prevalence and type distribution, HPV-related cancers, vaccination, screening and prevention. In 2006, the centre launched a series of international reviews published as scientific monographs and regional reports. To supplement these initial reviews, an international compilation of HPV and cervical cancer statistics for every country in the world was released in 2007. In 2008, the project published three volumes, which provided an updated overview of progress in the research field, an expanded understanding of the infection and disease spectrum, and gave information on the technical developments for the prevention of HPV-related diseases. The centre is now preparing the latest update of the general chapters describing scientific advances in the field. For more information, please visit: www.hpvcentre.net. Co-Directors: Xavier Castellsagué and F. Xavier Bosch Key Publication: Bosch FX, et al. Comprehensive Control of HPV Infections and Related Diseases Vaccine, Volume 30, Supplement 5, 2012. SCREENING C ervical cancer screening in Catalonia and beyond. UNIC has taken the lead in cervical cancer screening in Catalonia by spearheading the evaluation of screening activities and reviewing government recommendations. The unit was involved in writing the 2006 and 2015 screening recommendations for the Health Department of the Catalan Government and they continue to work towards the introduction of HPV testing in primary screening as a useful tool in the detection of persistent infection among women at-risk of cervical cancer. PI: Silvia de Sanjosé Key Publication: de Sanjosé et al. Screening of cervical cancer in Catalonia 2006-2012. Ecancermedicalscience 2015 29;9:532. Epub 2015 Apr 29. HPV VACCINE TRIALS E valuating the impact of HPV vaccination programmes. Prophylactic HPV vaccination is a powerful tool for primary prevention of cervical cancer and other HPV-related diseases. Since 2003, the group has been actively involved in seven Phase III trials evaluating the safety, immunogenicity and efficacy of the bivalent, quadrivalent and nonavalent prophylactic vaccines as well as a trial testing a therapeutic HPV vaccine. In addition, UNIC is carrying out Phase IV studies to assess the impact of the Catalan HPV Immunization Programme on the future burden of HPV-related diseases, including genital warts and cervical pre-cancers in Catalonia. Finally, the unit is also leading the FASTER project, a multinational study to assess novel preventative strategies combining HPV vaccination and HPV-based screening in adult women for a rapid and faster reduction of cervical cancer in Europe. PI: Xavier Castellsagué Key Publication: Bosch FX, et al. HPV-FASTER: broadening the scope for prevention of HPV-related cancer. Nat Rev Clin Oncol, 2015 Sep 1. doi: 10.1038/nrclinonc.2015.146. MODELLING M odelling and economic evaluation of cancer prevention measures. UNIC uses methods from decision science to address public health problems by developing and utilising a variety of mathematical models to perform cost-effectiveness studies in collaboration with Harvard University’s Center for Health Decisions Science (CHDS). Different analyses have been conducted that evaluate the risks, benefits and costs of various cervical cancer prevention strategies, including HPV vaccination and screening to inform health decisionmaking. UNIC has also used models to evaluate the impact of vaccination and screening in Spain, and has worked in collaboration on models for Asia, Latin-America, Africa and Europe. PI: Mirera Diaz Key Publication: Diaz M, et al. Cost-effectiveness of human papillomavirus vaccination and screening in Spain. Eur J Cancer. 2010 Nov;46(16):2973-85. doi: 10.1016/j. ejca.2010.06.016. Epub 2010 Jul 16. PubMed PMID: 20638840. OTHER ACTIVITIES EPILYMPH L aunched in 1998, EpiLymph is a multidisciplinary group of epidemiologists, haematologists and statisticians that evaluates the role of infectious, environmental and genetic factors in the aetiology of lymphomas. The EpiLymph group is involved in several consortia: the International Lymphoma Epidemiology Consortium (INTERLYMPH), the EPIC Lymphoma Working Group and the International Cancer Genome Consortium on Chronic Lymphocytic Leukemia (CLL)—working together in the epidemiological investigation of lymphoma worldwide. The group is currently leading the study on CLL in the MCC-Spain study examining the etiologic and prognostic factors of this disease. Co-PIs: Silvia de Sanjosé and Delphine Casabonne Key Publication: Nieters A, et al. Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH. Gastroenterology. 2006 Dec;131(6):1879-86. Epub 2006 Sep 20. PubMed PMID: 17087949. O perational since 2004, e-oncología is the first programme of its kind to offer specialised cancer training in Spanish. The web-based, e-learning platform represents a strategic alliance between the Catalan Institute of Oncology (ICO), the Spanish Society of Medical Oncology (SEOM), the International Federation of Gynecology and Obstetrics (FIGO), the International Atomic Energy Agency (IAEA) and the International Agency for Research on Cancer (IARC), among others. The programme strives to expand the boundaries of traditional training and generate knowledge networks among specialists, teachers and all professionals interested in oncology. The programme offers: • • • • • More than 200 professionals working as authors / tutors or course directors Courses in 8 languages, including Spanish, English, French, Russian and Portuguese An international, collaborative network that supports e-oncology An adaptable curriculum with courses tailored to the specific needs of each country and region International and national CME course accreditation To date, more than 17 000 individuals have participated in the programme and more than 2 300 hours of virtual teaching have been completed. Programme Director: F. Xavier Bosch Website: www.e-oncologia.org NUTRITION AND CANCER UNIT (UNAC) C omprised of a multidisciplinary group of epidemiologists, nutrition specialists, molecular biologists, geneticists, and statisticians, much of UNAC’s focus is conducting aetiological research on the relationship between nutrition and cancer. This includes mainly research on diet and dietary pattern, body composition and physical activity as possible determinants of cancer. UNAC’s interests also include the role of environmental factors as well as genetic susceptibility in human carcinogenesis. To achieve this, UNAC aims to combine traditional epidemiologic approaches with innovative tools, including the use of biomarkers of exposure and susceptibility. The unit is also developing new lines of research on the role of nutritional factors in disease prognosis and progression among cancer survivors. Most of UNAC’s research is carried out within the framework of the European Prospective Investigation on Diet, Cancer and Health (EPIC), in collaboration with the European Union, IARC/WHO and the Imperial College London. Contact Information: Nutrition and Cancer Unit (UNAC) Head of Unit: Antonio Agudo Email: [email protected] Phone: +34 932 607 812 Website: http://icoepi.net/nutrition-andcancer-unit/ EPIC-RELATED RESEARCH EUROPEAN PROSPECTIVE INVESTIGATION ON DIET, CANCER AND HEALTH (EPIC) E PIC is a multicentre, cohort study with a primary objective to investigate the relationship between nutritional status, lifestyle, genetic and environmental factors and the incidence of cancer and other chronic diseases. UNAC is engaged in several EPIC-related areas of research, leading the working groups on gastric, oesophageal and pancreatic cancers. In addition, UNAC works in close collaboration with other EPIC research groups studying lung, prostate, colorectal, bladder, cervical cancer, breast and other hormone-related cancers. EPIC has identified more than 90 000 cases of cancer and is one of the largest existing studies of this type in the world—with data from approximately 500 000 individuals followed for more than 15 years in 10 European countries, including Spain. For more information on the EPIC Study, please visit: http://epic.iarc.fr/index.php. GASTRIC CANCER E nvironmental factors, helicobacter pylori infection, genetic susceptibility and gastric cancer risk in the European population (EURGAST I and EUR-GAST II). One of UNAC’s main objectives is to advance European and international knowledge in the area of gastric cancer--the fifth most common malignancy and the third leading cause of cancer death worldwide. Research is still needed to elucidate the causes of this disease and to identify effective biomarkers for its early detection and prognosis, as well as identify specific targets for its treatment. EUR-GAST is a case-control study nested within the EPIC cohort, aimed to clarify the role of several environmental and genetic factors in the process of gastric and oesophageal carcinogenesis. Project activities include evaluation of the role of environmental factors, such as Helicobacter pylori and EBV infection, diet and circulating levels of nutrients and vitamins, alcohol consumption and smoking, on gastric cancer risk. The roles of epigenetic and genetic factors are also analysed. Other research lines and activities include: • factors and molecular mechanisms involved in the progression of gastric precancerous lesions to gastric cancer • validation in independent populations and functional characterisation of genetic susceptibility factors • analysis of factors involved in the progression and response to treatment of the disease • participation in two international GWAS on gastric cancer PI: Antonio Agudo Key Publication: González CA, et al. Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project. Ann Oncol 2012;23:1320-4. CANCER AND DIETARY PATTERNS T he role of a Mediterranean dietary. Dietary pattern analysis has become an increasingly important area of research in the study of dietdisease associations. Analysing food consumption as dietary patterns not only offers a new perspective from the traditional ‘single nutrient’ point-of-view, but may provide a more comprehensive approach towards disease treatment and prevention—facilitating translation into public health guidelines. UNAC’s primary lines of research in this field are the role of a Mediterranean diet and the inflammatory potential of diet. UNAC researchers are designing a project to investigate circadian clock systems and chronodisruption of diet in order to better understand the aetiology of obesity and related diseases such as type II diabetes and metabolic syndrome. DETAILS T T PI: Genevieve Buckland PI: Paula Jakszyn he role of a Mediterranean dietary. Adherence to a traditional Mediterranean diet is associated with significant reductions in chronic disease-related morbidity and mortality. UNAC researchers are active in the examination of the relationship between various Mediterranean dietary patterns and the risk of gastric and oesophageal cancers. Other areas of research include adherence to a Mediterranean diet and the risk of breast cancer and bladder cancer; a healthy lifestyle index encompassing the Mediterranean diet and gastric cancer; the Mediterranean diet and risk of myocardial infarction (EPIC-Spain). he inflammatory potential of diet. Studies have shown that various factors such as diet, abdominal adiposity and low levels of physical activity may be the origin of a phenomenon known as ‘low-grade chronic Inflammation’, the physiological basis of several chronic diseases and the development of various tumours. Starting with the Spanish EPIC cohort, UNAC is working to develop models to estimate the potential risk of an inflammatory diet and to assess its possible relationship with the risk of several malignant tumours and mortality. Key Publication: Buckland G et al. Adherence to the Mediterranean Diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study. Int J Cancer 2013; 132:2918-27. PANCREATIC CANCER I nvestigation of cancer of the pancreas. Pancreatic cancer is the most lethal of all cancers; with 5-year survival at 5-7%. Currently, most cases of pancreatic cancer are identified well after the disease has metastasised (spread) to other organs in the body. Other than surgery, which is an option for about 15% of patients, there are no effective treatments for pancreatic cancer. Thus, identifying the disease early with the use of non-invasive blood-based biomarkers is an urgent research priority. Primary prevention is also a research priority; however, complete understanding regarding the causes of the disease are lacking. UNAC conducts and collaborates on a number of international epidemiological studies, within the EPIC cohort, and two international consortia– PanC4 (The Pancreatic Cancer Case-Control Consortium) and PanScan (The Pancreatic Cancer Cohort Consortium), as well as the following lines of research: • genetic susceptibility, genome-wide association, and gene-environment interactions • toxic metals (dietary and environmental) and pancreatic cancer risk in the EPIC cohort • evaluation of markers of epigenetic dysregulation as biomarkers of early disease detection • role of common infections • dietary consumption and pancreatic cancer • healthy lifestyle and preventing pancreatic cancer • role of a Mediterranean diet in pancreatic cancer • hormonal factors and gender differences in pancreatic cancer incidence PI: Eric Duell Key Publication: Duell EJ et al. Association between pancreatitis and pancreatic cancer risk in the international pancreatic cancer case-control consortium (PanC4). Ann Oncol 2012; 23:2964-70. NUTRITIONAL EPIDEMIOLOGY N utritional epidemiology is the study of human health in relation to nutrition. What started as a small sub-discipline of epidemiology has now grown into a significant field of public health importance. The EPIC study has collected data on the dietary habits of more than 500 000 people in 10 European countries; moreover the collection of detailed data on other lifestyle factors, can be used to correct diet—disease associations for potential confounding bias. Being one of the largest prospective cohort studies on nutrition, the EPIC study has detected novel associations and provided considerable evidence for existing hypotheses. Furthermore, UNAC has made valuable contributions to the field through its research on the consumption of fruits and vegetables, meat and meat-related components such as N-nitroso-compounds and endogenous nitrosation, dietary flavonoids and polyphenol intake. DETAILS Key Publication: González CA et al. Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 2006; 98:345-54. BIOMARKERS R esearch on dietary biomarkers related to cancer and nutrition. In recent decades, cancer research has used biochemical markers with a focus on: better defining exposure, improving early detection, refining susceptibility, increasing understanding of disease aetiology and improving treatment. Although most work nutritional epidemiology from the EPIC study used data from dietary questionnaires, an increasing amount of research in the past decade has made use of nutritional biomarkers to assess exposure, as well as to identify genetically-susceptible individuals at high-risk of cancer. However, evidence establishing a causal link between biomarkers of specific dietary constituents and cancer is lacking. UNAC researchers have made valuable contributions in this area. Major findings include associations of haemoglobin adducts of acrylamide with endometrial and ovarian cancers; aromatic adducts with gastrointestinal, lung, and breast cancers and; markers of iron homeostasis with gastric adenocarcinoma, UNAC has also initiated research on the effect of Bisphenol-A in breast and prostate cancers and in cardiovascular disease as well as research to identify a biomarker of olive oil. Additional research includes the analysis of the levels of diet and other lifestyle factors in relation to serum levels of organochlorine pesticides and PCBs, as well as with the adduct levels of acrylamide and aromatic compounds such as polycyclic aromatic hydrocarbons. DETAILS Key Publication: Fonseca-Nunes A et al. Body iron status and gastric cancer risk in the EURGAST study. Int J Cancer 2015;137:2904-14. RESEARCH ON CANCER SURVIVORSHIP P revention of Breast Cancer Recurrence Through Weight Control, Diet, and Physical Activity Intervention. There is growing interest regarding the potential role of nutrition in the prognosis and progression of disease in cancer survivors; particularly for cancer that are causally related to diet. Recent advances in breast cancer treatment and improved screening have resulted in an increased number of survivors. However, since recurrences are still a relatively common event, there is a critical need to investigate modifiable factors that could impact disease recurrence and long-term prognosis. There is substantial evidence from observational studies showing that weight management, increased physical activity and dietary modification may be effective methods to reduce recurrences and improve survival. To confirm the role of these lifestyle factors on breast cancer, further research is needed to establish specific lifestyle recommendations. UNAC coordinates a multicentre, randomised clinical trial (PREDICOP) aimed to assess the effect of a lifestyle intervention combining weight control, diet and physical activity on the risk of relapse among breast cancer patients, as well as the effect of the intervention on survival and quality of life. This trial will include about 200 women aged up to 75 years, diagnosed with non-metastatic breast cancer (stage I, II, IIIA). Participants will be assigned to either an intervention or a control group, and followed for five years. Patients in the intervention group will be involved in a lifestyle programme with two components. The dietary part will aim to achieve a calorie reduction while maintaining nutritional quality; the physical activity part will include supervised sessions of moderate intensity. PI: Antonio Agudo; Project Managers: Noemie Travier, Genevieve Buckland Key Publication: Travier N et al. Effects of an 18-week exercise programme started early during breast cancer treatment: a randomized controlled trial. BMC Med 2015; 13:121. OTHER ACTIVITIES U NAC researchers have participated several EPIC-related lines of research investigating environmental and reproductive factors as well as molecular and genetic epidemiology, including one area of investigation with particular relevance: the impact of tobacco smoking. Other interests include factors related with overall health and mortality and factors related to obesity and weight change (the PANACEA study). UNAC researchers are also active in several international consortia, including ARCAGE / INHANCE, Panc4 and ILCCO. Key Publication: Agudo A et al. Impact of cigarette smoking on cancer risk in the European prospective investigation into cancer and nutrition study. J Clin Oncol 2012; 30:4550-7. Meet PREC’s Team INFECTIONS AND CANCER UNIT NUTRITION AND CANCER UNIT RESEARCH SUPPORT Leadership Team Leadership Team Administrative Team Silvia de Sanjosé Programme Director Silvia de Sanjosé Programme Director Cristina Rajo Head of Research Project Management Xavier Castellsagué Infections and Cancer, Head of Unit Antonio Agudo Nutrition and Cancer, Head of Unit Ángela Expósito Administrative Assistant – Nutrition and Cancer Unit F. Xavier Bosch Senior Consultant to PREC Ion Espuña Administrative Assistant – Infections and Cancer Unit Scientist Group Scientist Group Ginesa Albero, Research Assistant Eric J. Duell, Researcher Marta Aldea, Research Assistant Nadia García, Technician Laia Alemany, Researcher Carlos A González, Emeritus Researcher Leslie Barrionuevo, Research Assistant Paula Jakszyn, Researcher and Associate Professor Yolanda Benavente, Research Assistant Leila Luján, Research Assistant and Associate Professor Maria Brotons, Researcher Mireia Obón, PhD Student Laia Bruni, Researcher Núria Sala, Researcher Vanesa Camon, Technician Noemie Travier, Research Assistant Delphine Casabonne, Researcher Raul Zamora, Researcher Omar Clavero, Researcher Laura Costas, Researcher Mireia Diaz, Researcher and Associate Professor Ana Esteban, Technician Marta Félez, PhD Student Yolanda Florencia, Technician Nati Patón Administrative Assistant – Infections and Cancer Unit IT Team Jesus Muñoz IT Manager Xesco Alarcón IT Assistant E-oncología Team Assumpta Company Academic Director Natalia Casal Learning Technician Olga Guillen Learning Technician Mireia Montserrat Learning Technician Raquel Ibáñez, Research Assistant Marisa Mena, Researcher Beatriz Mengual-Chuliá, PhD Student Sara Nicolàs, PhD Student Ville Nikolai, Researcher Beatriz Quirós, Technician Vanesa Rodríguez, PhD Student Esther Roura, Research Assistant Beatriz Serrano, Research Assistant Miren Taberna, Researcher Sara Tous, Research Assistant Marleny Vergara, Technician CONTACT US Cancer Epidemiology Research Programme Institut Català d’Oncologia (ICO) Av. Gran Via de l’Hospitalet 199-203 08908 L’Hospitalet de Llobregat (Barcelona) Spain Tel.: +34 932 607 812 • +34 932 607 401 Fax: +34 932 607 787 [email protected] http://icoepi.net http://ico.gencat.cat/en/