Current Scientific Initiatives Mechanisms of Carcinogenesis Section (MCA) Zdenko Herceg, PhD Cancers are the consequence of combined genetic and epigenetic changes induced by environmental exposures MCA Section • The goal of the MCA Section is to advance understanding of mechanisms of carcinogenesis and to contribute to biomarker discovery • This is achieved through investigating interactions between the genes, the epigenome and the environment • MCA also develops genetic/epigenetic methodologies that are applicable to biobanks associated with epidemiological studies Research Groups • Molecular Mechanisms & Biomarkers (MMB) – Magali Olivier (Acting) • Epigenetics Group (EGE) – Zdenko Herceg Early genetic changes (“drivers”) in cancer and their links with environmental exposures • Molecular events (somatic mutations) can be “read” as fingerprints of exposures and mechanisms of mutagenesis • Majority of studies investigated genetic changes in cancer tissues, less is known about key early changes that promote tumour development • Advances in genomics and major sequencing initiatives have opened an opportunity for identification of target genes of environmental factors Research aims • Identify molecular events (mutations) that drive the process of tumour initiation/progression and distinguish them from “passenger” events • Identify environmental factors associated with these “driver” changes • Contribute to the discovery and validation of new cancer biomarkers with an emphasis on cancers associated with low-resource countries Impact of early life exposure on the epigenome and cancer risk in childhood and adulthood Parental exposures Maternal diet/lifestyle Conception Windows of susceptibility Gametes In utero life Birth Epigenome reprogramming Exposure markers Childhood Leukemia Epigenetic profiling Adulthood Cancer Cancer risk Epigenetic deregulation induced by early life exposure and cancer risk • Adaptive responses during early life may deregulate developmental pathways (expansion of somatic stem cells, metabolic changes, hormones), which may alter susceptibility to cancer in later life • Mechanisms by which early-life events fix and propagate deregulated gene activity states and alter cancer risk (DNA methylation, non-coding RNAs) Research aims • Employ powerful epigenomic tools (NGS approaches) to perform epigenomic profiling of samples taken at birth • Take advantage of mother-child cohorts for which the recruitment has been completed (I4C consortium, Gambia) • Identify “epigenetic signatures” associated with exposures and assess whether epigenome changes at birth can predict future risk of cancer Questions • Potential models and approaches to discriminate between “driver” and “passenger” events? – In vitro, in silico… • What criteria should we apply to define a set of priority exposures to be addressed in a systematic way? – Feasibility, synergy with other programmes (life-styles, hormones) – Relevance to low-resource settings • Can we detect exposure-associated and cancer-associated epigenetic changes in surrogate tissues as biomarkers? – Biospecimens (cord blood, blood spots, peripheral blood) – Technological platforms Role of human papillomavirus infection and cofactors in the etiology of cancer and precancerous lesions of head and neck in Europe and India Massimo Tommasino Section of Infections Scientific Council Forty-eighth Session, 1-3 February 2012 Section of Infections (INF) IARC Director Section of Infections (INF) Head: Silvia Franceschi Infections and Cancer Biology Group (ICB) Head: Massimo Tommasino Infections and Cancer Epidemiology Group (ICE) Head: Silvia Franceschi Section of Infections AGENTS INCLUDED ASPECTS UNDER STUDY • • • • • • Worldwide distribution and trends over time of infections associated with cancer Range of tumours associated with infection and strength of the association Transformation mechanisms Meaning of viral variants Role of innate and acquired immunity New virological and bacteriological tests for epidemiological studies • • • • • • Mucosal and cutaneous human papillomavirus types HIV, in combination with other viruses associated with cancer Helicobacter species Hepatitis viruses Epstein Barr virus Merkel cell polyomavirus Role of HPV in non-genital cancers Head and Neck (H&N) HR HPV (<5%) Oro-pharynx High-Risk (HR) HPV (10-50%) (Limited studies mainly in USA and Europe) Cervix HR HPV (100%) Vagina HR HPV (70%) Vulva HR HPV (40%) Penis HR HPV (40%) Anus HR HPV (100%) HPV infection: cervix vs. oropharynx CERVIX OROPHAYNX TRANSMISSION Sexual intercourse Age 1st acquisition? Common, N worldwide ? HPV 16 50% of cervical carcinomas 90% of HPV+ oropharyngeal carcinomas PRECANCEROUS LESIONS Well-defined (CIN) ?? OTHER RISK FACTORS Only in cooperation with HPV (weak) Tobacco, alcohol (very strong) New INF projects on HPV and cancers of the head and neck (H&N) • SPLIT project: prevalence of HPV and precancerous lesions in tumor-free tonsil and differences in the natural history of HPV-associated and tobaccoassociated tonsil precancerous and cancerous lesions (PI: Silvia Franceschi) • HPV-AHEAD: multifaceted project investigating the role of HPV infection and other risk factors in H&N cancer incidence and outcome in Europe and India (PI: Massimo Tommasino) Study of papillomavirus & precancerous lesions in the tonsils (SPLIT protocol) No Participant Organization Name PI City 1 International Agency for Research on Cancer Silvia Franceschi Gary Clifford Jean-Damien Combes Massimo Tommasino Lyon 2 Service d'ORL et Chirurgie Cervico-Faciale Hôpital Tenon (AP-HP) and Université Pierre et Marie Curie (UFR) Jean Lacau St Guily Sophie Perie Isabelle Brocheriou Marine Lefevre Roger Lacave Patrick Soussan Paris 3 INSERM UMRS-903 CHU Reims, Hôpital Maison Blanche Laboratoire Pol Bouin : Histologie – Cytologie Christine Clavel Philippe Birembaut Véronique Dalstein Reims Participating clinical centres (n=16): CHU Besançon; Caen; Lyon-Sud; Nantes; Nîmes; Paris Bichat; Paris Debré; Paris Foch; Paris Necker; Paris Pitié; Paris Tenon; Paris Trousseau; Poitiers; Toulouse; Tours; Reims; Strasbourg Hautepierre. Main activities of the consortium Benign tonsils (exfoliated cells and frozen tissue) Specimen collection Age group Pediatric Age (years) <4 Sample size 100 Young adults Older adults 5-14 15-24 25-34 35-45 >45 100 100 100 100 200 Plus 50 tonsillar carcinomas to assess severe dysplasia adjacent to cancer Laboratory analyses • Cytological (brushing) and in-depth histological analyses • HPV genotyping (two assays, including multiplex-Luminex for 78 infectious agents) • Search for biomarkers for carcinogenesis by immunohistochemistry Outcome of the SPLIT study • Establishment of the prevalence of HPV infection in cancer-free tonsils of children and adults and age at acquisition • Identification of tonsillar precancerous lesions in highrisk groups (HPV-pos and heavy smokers ≥35 yrs) • Characterization of possible differences between HPV-positive and HPV-negative precancerous lesions Role of human papillomavirus infection and other co-factors in the aetiology of head and neck cancer in Europe and India (HPV-AHEAD) No Participant Organization Name PI Country International Agency for Research on Cancer (IARC) M. Tommasino R. Sankaranarayanan P. Brennan D. Forman M. Mendy France 2 Deutsches Krebsforschungszentrum (DKFZ) M. Pawlita Germany 3 Fundació Privada Institut D'Investigació Biomedica de Bellvitge (IDIBELL) FX. Bosch X. Castellsagué L. Alemany Vilches Spain 4 University of Antwerp (UA) M. Arbyn M. Peeters JP.Bogers Belgium 5 Istituto Europeo di Oncologia (IEO) F. Chiesa S. Chiocca Italy 6 Aristotle University of Thessaloniki (AUTH) G. Mosialos Greece 7 German Institute of Human Nutrition (DIfE) H. Boeing Germany 8 Universitätsklinikum Heidelberg (UKH) G. Dyckhoff Germany 9 MTM Laboratories AG (MTM) R. Ridder Germany 10 Rajiv Gandhi Centre for Biotechnology (RGCB) R. Pillai India 1 (Co) Main activities of the consortium WP2, 5 Specimen collection • head & neck cancer specimens from 44 European (n=6,000) and 6 Indian (n=5,000) centres • 4,000 sera from controls and cases • Approximately 1,000 oral specimens (exfoliated cells) from healthy and cancer individuals WP3, 5, 6 WP1,4 WP7 Laboratory analyses Epidemiological studies Training and transfer of technology • HPV genotyping • HPV-positivity at different anatomical sites and geographical regions • HPV genotyping platforms in India • Expression of viral oncogenes (E6 and E7) • Immuohistochemical analyses • MicroRNA expression in HPV-positive and HPV-negative HNCs • Trend of HPV positive cancers in the last decades • Interaction of HPV infection and other risk factors • HPV serology • Link between HPV positivity and favourable prognosis of HNC • Summer school on oncogenic viruses • Mini-symposium on HPV-associated cancers Outcome of the HPV-AHEAD study • Better determination of the incidence of HPV-positive HNCs in Europe and India that are exposed to different environmental factors • Confirmation whether HPV-pos HNCs incidence is increasing in relative and/or in absolute terms • Characterization of the natural history of HPV infection in the upper aerodigestive tract • Evaluation of possible interactions between HPV and other risk factors in the H&N carcinogenesis • Identification of surrogate markers of HPV infection in the upper aerodigestive tract Requested input from the SC Suggestions for additional issues/approaches to be included in these studies that have just started Current questions (i) What is the fraction of HNC and precancerous lesions truly attributable to HPV in different populations? (ii) Are there differences between HPV-related HNC and precancerous lesions and those caused by other risk factors, notably smoking? (iii) What is the scope for decreasing HNC incidence and mortality using prevention strategies (HPV vaccination of adolescents of both sexes) and new treatment approaches that are becoming available specifically for HPV-associated carcinomas? Nutrition and Metabolism NME Dr Isabelle Romieu Nutrition and Metabolism Section Section Head: Dr Isabelle Romieu Dietary Exposure Assessment Biomarkers Head: Nadia Slimani, PhD Head: Augustin Scalbert, PhD Implement international dietary methodology and study dietary exposure in developed and in transition countries Develop and implement of new biomarkers to improve assessment of diet, physical activity, obesity and exposure to environmental risk factors Nutritional Epidemiology Head: Isabelle Romieu, MD, MPH, ScD Conduct epidemiological studies to evaluate the association of diet, physical activity, obesity and life style with cancer risk in developed and in transition countries PRECAMA: Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women Multicenter population based case-control study • Breast cancer is a leading cause of death in Latin America • Large number of incident cases among premenopausal women • Little information on breast cancer phenotypes and specific risk factor • Limited data suggest more aggressive types of tumours • BC in Hispanic could comprise distinct subtypes likely to have different risk factor profiles • Major relevance for treatment and preventive actions Participating countries: Brazil, Chile, Colombia, Costa Rica and Mexico Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women • Standardized protocol for clinical and exposure data, biological specimens, and tumor sampling and analyses • Recruitment of 500 cases/500 controls per centers ( expected 2000 cases/ 2000 controls) • Molecular subtypes of premenopausal BC (FHCRC and MAC, IARC) – Classification into Luminal A, Luminal B, Basal like, HER2+/ER- based on IHC biomarkers (ER,PR, HER2, EGFR,CK5/6, Ki67) – Analyses of tumor DNA for TP53 mutations (classification into non mutated (WT) and mutated subtypes) • Identification of specific endogenous risk factors for specific subtypes of BC – DNA extraction from lymphocytes to assess population admixture (AIMS), mutations in BC susceptibility genes (BRCA1, BRCA2,TP53) and specific SNPs Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women • Exogenous risk factors for specific subtypes of BC – – Socio-demographic factors, ethnicity, reproductive and clinical history, use of hormones and family history of cancer Body silhouette at different ages – Anthropometric measurements – Life style factors • Occupation, environmental risk factors • Diet (FFQ) • Physical activity – Biomarkers (blood) • Lipid profile, C-peptide, CRP, IGF1, IGFBP3, estrone • Nutritional biomarkers such as folate, vitamin D and fatty acids – Metabolomic analyses (urines) Metabolomic approach for dietary assessment • A number of foods and nutrients not easily assessed through questionnaires – Lack of accurate composition data – Bias in self-reporting • Metabolomic approach to provide a broad coverage of biomarkers for dietary assessment taking into account both intake and metabolism – Biomarker discovery – Biomarker implementation • Biomarkers for dietary factors related to cancer risk • Fruits and vegetables • Meats • Dietary pattern • Fibers • Polyphenols 375 polyphenol metabolites 5500 5000 4500 Improved assessment of exposure to polyphenols in EPIC 17.103 - 14_0 7500 7000 6500 6000 20 25 30 35 - 20_5n3 A38.808 re a: 28 73 - 24_0 A40.558 re . 8 a: A41.384 - 22_4n6 3 - 24_1n9 A41.581 re 7r0ea a42.376 : 2 .6:913 - 22_5n6 3. 5810 74 .8 - 22_5n3 19 43.918 5 8000 ea 22 : 2 86 6 .1 44.971 - 22_6n3 ea :3 .4 82 25 .4 53 62 .3 20_3n6 36.207 -Ar 20_4n6 ea :5 03 28.669 -Ar 18_2n6 2 25.544 Ar - 18_0 ea : 26.623 - A18_1n9c r 4 ea 1 : 696 9996 32.7 .6 counts 20.331 - A16_0d31 r 21.000 Area-: 16_0 A comprehensive database on polyphenols and their metabolites - 14_1n5 A18.347 reA18.935 - 15_0 ar : ea8 :14.7 4162 .8 23 - 16_1n9t A21.808 re A22.156 - 16_1n7 a: re 7 a: - 17_0 A23.144 re5.8 15 a: 81 75 94 9 .1 5 4. 28 9 - 18_1n9t A26.295 re - 18_1n7c A26.825 a: re 74 a: A27.915 .2 - 19_0 26 re 66 41 a: 5 .6 13 7 2. 02 - 18_3n6 A30.126 A30.435 6 - 20_0 rreea - 18_3n3 : A31.100 ra: 3 - 20_1n9c A31.537 reea1: 1189. a: 49.293 33 5.921 0. 80 31 9 - 20_2n6 A33.630 re a: 5 11 A35.088 37 re a: .8 7 11 05 8. 8 The polyphenol metabolome assessment • Dietary polyphenols, major antioxidants of the diet, may play a role in cancer prevention • Difficult to assess polyphenol intake because of a large diversity of structures and wide distribution in foods Mass spectrometry-based methods to characterize the polyphenol metabolome FID1 A, (E:\GC1\DATA1\TEST\016B1901.D) 4000 40 45 mi Some questions • The classification used to characterise tumour subtypes include classical markers plus other markers such as TP53 mutations – Suggestions on other potentially useful markers? • We include exogenous and endogenous characteristics and hypothesize that specific subtypes of tumours will have different sets of risk factors – Other potential risk factors or specific hypotheses of interest? – Virus infection to be considered? • Biomarkers for dietary assessment – Which foods/nutrients to consider in priority? – Suggestions for other innovative approaches? Section of Genetics (GEN) Dr Paul Brennan, Section Head Overview of the Section – Cancer sites: • Lung, Head & Neck, Kidney • Rarer cancers (e.g. Hodgkin Lymphoma; Nasopharyngeal cancer) – Areas of expertise: • • • • Genetic and molecular epidemiology Field work Genomics and bioinformatics Biostatistics – Research Groups: • Genetic Epidemiology (GEP) – Dr Paul Brennan • Genetic Cancer Susceptibility (GSC) – Dr James McKay • Biostatistics (BST) – Dr Graham Byrnes Renal cancer genetic epidemiology MP Purdue, M Johansson, D Zelenika, JR Toro, G Scelo, LE Moore, et al. 2p21: EPAS1 (HIF-2α) – key gene in VHL-HIF pathway – interaction with smoking 11q13: gene unknown 12q24: SCARB1 – further replication needed – mediates cholesterol uptake – Funding obtained to extend the study: • Double the size of the study, reaching up to 10,000 cases and 15,000 controls in collaboration with the NCI cohort consortium initiative • Include survival component • Integrate analysis with transcriptomic data – What additional opportunities does this new collaboration with the cohort consortium offer? Lung cancer genetics Current initiative • Part of an NCI U19 grant for transdisciplinary research in lung cancer • Meta-analysis of 16 GWAS, reaching 15,000 cases and 29,400 controls • Identification of 2 new candidate loci associated with squamous cell carcinoma occurrence CHRNA5‐CHRNA3‐CHRNB4 TERT‐CLPTM1L BAT3‐MSH5 CDKN2B RAD52 Future plans 1. Develop a large biorepository for early-stage cases (I, II, and IIIa) • Investigate lung cancer outcome • Recruitment underway in Russia and Serbia (tumour tissue available in 300 cases) • Recruitment piloted in Poland, Czech Republic, and Romania 2. Whole-exome sequencing or high-density genotyping? Lung cancer cohort consortium (LC3) Johansson M, Relton C, Ueland PM et al. 2010 – Possible important role of circulating vitamin B6 and methionine in lung cancer etiology – Funds obtained for a large cohort consortium project with 26 cohorts, including 12,000 lung cancer cases with biosamples available – Serum measurements of ~40 biomarkers related to one-carbon metabolism on equal proportions of never, former and currents smokers (n = 1,200 x 3 from EU/US cohorts), and 1,500 Asian cases + matched controls in a centralized laboratory – LC3 will provide the framework for other large-scale genetic and non-genetic studies on lung cancer etiology using high quality prospectively collected data (e.g. biomarkers prior to onset): Should this be of priority for the Agency? Genetics of Head and Neck cancers et al. 8,600 H&N cancer cases and 16,000 controls Five variants/Three loci achieved p < 5x10-7 rs Chr Gene Future plans: Combined rs1229984 4q23 ADH1b 0.62 5x10-21 – Whole-exome sequencing of 50 tumour-germline DNA pairs (using IARC newly acquired platform) rs1573496 4q23 ADH7 0.75 5x10-17 – Focus on oropharyngeal cases rs698 4q23 ADH1c 1.12 3x10-7 -8 OR Pts rs4767364 12q24 ALDH2 1.13 7x10 – By HPV tumour DNA status (testing ongoing) rs1494961 HEL308 1.12 2x10-8 – Parallel study with INCA Brazil 4q21 InterCHANGE Study – H&N is the 4th most common cancer in Brazil – Primary goal: identify genetic and other biomarkers associated with H&N cancer onset and outcome – Plans for 2000 cases and corresponding controls nation-wide – Enhance collaboration between major cancer centers in Latin America and with IARC – Obtain high quality clinical and outcome data – Extensive biosample collection (tumour an adjacent non-tumour tissue, blood, diagnosis slides) and repeat blood collection after onset Development of large biorepositories Summary • Representative of many countries, and with harmonized collection protocols • Extensive collection (blood, slides, frozen tumours, and more recently nontumour target organ tissue samples) • Comprehensive annotations of samples: pathological review data, clinical data, but also survival and lifestyle data Main collections Target organs From case-control studies (existing and ongoing) From cohort prediagnosis samples (planned) Kidney N=2000 cases (+ corresponding controls) 1000 with tumour samples 400 with tumour-normal tissue pairs Russia and central Europe N=1000 cases (+ corresponding controls) All with germline DNA and serum/plasma Western Europe, US, and Australia Lung N=5000 cases (+ corresponding controls) 800 with tumour samples 200 with tumour-normal tissue pairs Russia and central Europe N=5000 cases (+ corresponding controls) All with germline DNA and serum/plasma Western Europe, US, Australia, and Asia Head and Neck N=3000 cases (+ corresponding controls) 1200 with tumour samples Europe and Latin America Future plans for N=2000 cases All with germline DNA and serum/plasma Western Europe, US, Australia and Asia Main questions for the SC Given the large case-series and cohort consortia that GEN is coordinating, a major question is whether we should consider, in addition to our main hypotheses, trying to develop pre-diagnosis signatures for these cancers, based on circulating biomarkers and genetic profiles. Similarly, to what extent should we try to identify blood or tissue based marker for outcome? Main questions for the SC Specific questions: (i) Are there sensitive methods for measuring circulating tumour DNA that are ready for broader evaluation; (ii) Are there promising metabonomics or proteomics techniques that we should consider testing on subgroups of these cases (e.g. those diagnoses shortly after provided a blood sample, or even in separate case series); and (iii) Should we consider additional markers of subsequent cancer risk including telomerase regeneration or markers of inflammation. Such studies may also require collection of tumour tissue within the cohorts, and the relative priority to place on this is unclear, especially when one can focus on collection of better annotated samples from prospective case series. Early Detection and Prevention Section EDP Dr R. Sankaranarayanan Prevention and Implementation Group Quality Assurance Group Screening Group Dr R. Herrero Dr L. von Karsa Dr R. Sankaranarayanan Prevention and Implementation Group Eradication of Helicobacter pylori to prevent stomach cancer Burden of stomach cancer and association with H. pylori infection • Second cause of cancer death • Estimated 75% caused by H. pylori • No scientifically established risk biomarkers among H.pylori positive • Potential biomarkers: CagA, pepsinogen I/II ratio, genetic polymorphisms • Eradication is feasible with antibiotics, recurrence is limited, some impact on stomach cancer risk – RR=0.65 (0.43-1.01) in meta-analysis (Ford, 2011) – More effective before precancer – Prevents metachronous cancers Potential benefits and harms of H.pylori eradication Benefits • Stomach cancer control • Peptic ulcer reduction • Dyspepsia reduction • Better nutritional status • Fewer healthcare visits Harms • Resistance organisms • Drug side effects • Altered immunity • Obesity • Esophageal cancer Ongoing randomized trial in China • 200,000 residents (25-54 years) Linqu County • Screening with Urea Breath Test (70% positivity expected) • Randomization to Omeprazole, Tetracyclin Metronidazole, Bismuth (OTMB) vs. OB • 10-year follow up for incidence and mortality Classen M and You W, personal communication, with permission Design of randomized clinical trial Exposures/Subgroups • Age • Sex • Region • Biomarkers • Precursor lesions • Treatment Outcomes • Stomach cancer • Peptic ulcer • Dyspepsia • Adverse events • Obesity • Asthma • Esophageal cancer • Antibiotic resistance Questions for the Scientific Council • Eradication without more trials? • Multicentric clinical trial to evaluate impact of eradication • What is the ideal design? – – – – – Cluster vs. individual randomization Age groups to include Active vs. passive follow up Screening for surrogate outcomes or early cancer Follow-up logistics and duration, study size, cost • Ethical considerations • Organization of meeting of experts Quality Assurance Group Colonoscopic surveillance following adenoma removal Rationale • Colorectal cancer, 4th in mortality • Develops over several years (adenomacarcinoma sequence) - screening • Screening (FOBT) + colonoscopy find many more precursors (adenomas) than cancer • Cancer risk predicted by age, sex, size, morphology, pathology and number of detected adenomas Schematic overview of the adenoma-carcinoma sequence Projected annual progression of advanced adenomas H. Brenner et al. Gut 2007 Women • Advanced adenoma: • Size: >10mm • Morphology: tubulovillous or villous • Pathology: high grade dysplasia Rationale for investigation • Wide variation in surveillance, resource intensive • Limited evidence from small prospective studies (pooled < 10,000 subjects) • Less resource-intensive approaches needed to improve benefit-harm balance and costeffectiveness: • Better risk stratification • Less frequent colonoscopy • Alternative surveillance test (immunochemical FOBT?) Multinational, randomized trial, surveillance and natural history • Nested in population-based programmes to reduce cost, improve feasibility • Eligibility: Medium and/or high risk groups • Study arms: Different delays in time to first surveillance and follow up intervals • Controls: Immunochemical FOBT • Endpoints: Precursor lesions and cancer • Fail-safe: Threshold of acceptable risk Questions • Are the limitations of available evidence for current practice sufficient justification for reduced surveillance in some study arms ? • If not, could the study be conducted in areas where no surveillance is in place? • Should IARC pursue such investigation? Medium-term Future of IARC Handbooks on Cancer Prevention Section of IARC Monographs (IMO) • • • • Prevention is probably the single most effective response to the rising burden of cancer, particularly in LMIC. The first step in cancer prevention is to identify the causes of human cancer. The IARC Monographs evaluate the potential carcinogenicity of chemicals, complex mixtures, occupational exposures, physical and biological agents and lifestyle factors. “The encyclopaedia of carcinogens”: since 1971 more than 900 agents have been evaluated ¾ 107 are carcinogenic to humans (Group 1) ¾ 61 are probably carcinogenic to humans (Group 2A) ¾ 269 are possibly carcinogenic to humans (Group 2B) History of Cancer Prevention HBs • Launch in 1995 to complement the IARC Monographs’ evaluations of carcinogenic hazards with evaluations of cancerpreventive agents. • Working procedures and evaluation scheme closely mirror those of the Monographs. • For the Tobacco Control HB, IMO scientists helped develop the series, when institutional memory was no longer available. • Monographs and Cancer Prevention HBs existed in parallel for the past 15 years. History of IARC Cancer Prevention Handbooks IARC Sc Pub #139 Principles of Chemoprevention (Nov 1995) Preventive Agents Vol 1 NSAIDs Vol 2 Carotenoids Vol 3 Vitamin A Vol 4 Retinoids Vol 5 Sunscreens Vol 6 Weight Control & Physical Activity Vol 8 Fruit and Vegetables Vol 9 Cruciferous Vegetables,Isothiocyanates and Indoles Screening Vol 7 Breast Cancer Screening (Working procedures) Vol 10 Cervix Cancer Screening Tobacco Control Vol 11 Reversal of Risk after Quitting Smoking Vol 12 Methods for Evaluating Tobacco Control Policies Vol 13 Evaluating the Effectiveness of Smoke-free Policies Vol 14 Effectiveness of Price and Tax Policies for Control of Tobacco Potential future of IARC Cancer Prevention Handbooks • • • • Currently, future of Cancer Prevention HBs is open (no dedicated unit and staff, no budget) Proposal to re-broaden scope of Handbooks (preventive agents, cancer screening) Section of the IARC Monographs to be in charge Medium-term merging of Monographs and Handbooks? Some additional considerations: • Key players and/or competitors • Potential funding sources (agencies, charities, Participating States) ? Decision on topics for IARC Cancer Prevention Handbooks Potential future topics for IARC Cancer Prevention Handbooks Re-evaluation of agents and first time evaluations Preventive Agents NSAIDs (Aspirin) Weight Control & Physical Activity Fruits and Vegetables, Vitamin B(6), Vitamin D Screening (new modalities, cultural context, LMIC) Breast Cancer Screening Cervix Cancer Screening Colorectal cancer Lung cancer Prostate cancer Oral cancer Tobacco Control ? Specific questions to be addressed by the SC 1) Does the SC support the initiative to re-broaden the scope of the Handbooks into preventive agents and cancer screening? 2) At an IARC-internal discussion on the future of the Handbooks, the following topics have been considered as high priority: a) Effectiveness of screening for prostate cancer b) Effectiveness of screening for colorectal cancer c) Aspirin as a cancer-preventive agent Which agents would the SC consider of high priority for (re)evaluation by the Handbooks? 3) Should future Handbooks continue to include recommendations for public health action?