Current Scientific InitiativesMechanisms 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

BirthBirthGametesGametes ChildhoodChildhood AdulthoodAdulthood

Epigenome reprogrammingEpigenome reprogramming CancerCancerLeukemiaLeukemia

Parental exposuresParental exposures Maternal diet/lifestyleMaternal diet/lifestyleC

once

ptio

nC

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In utero lifeIn utero life

Windows of susceptibilityWindows of susceptibility

Epigenetic profilingEpigenetic profiling Cancer riskCancer riskExposure markersExposure markers

Impact of early life exposure on the epigenome and cancer risk in childhood and adulthood

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

Scientific CouncilForty-eighth Session, 1-3 February 2012

Role of human papillomavirus infection and cofactors in the etiology of cancer and precancerous lesions of head and neck

in Europe and India

Massimo TommasinoSection of Infections

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 (INF)IARC Director

Section of InfectionsASPECTS 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

AGENTS INCLUDED

• Mucosal and cutaneoushuman papillomavirus types

• HIV, in combination with other viruses associated with cancer

• Helicobacter species• Hepatitis viruses• Epstein Barr virus• Merkel cell polyomavirus

Oro-pharynxHigh-Risk (HR) HPV (10-50%)

Cervix HR HPV (100%)Vagina HR HPV (70%)Vulva HR HPV (40%)Penis HR HPV (40%)Anus HR HPV (100%)

Role of HPV in non-genital cancers

Head and Neck (H&N)HR HPV (<5%)

(Limited studies mainly in USA and Europe)

HPV infection: cervix vs. oropharynx

CERVIX OROPHAYNXTRANSMISSION

Sexual intercourse Age 1st acquisition? Common, worldwide ?

HPV 1650% of cervical carcinomas 90% of HPV+ oropharyngeal

carcinomasPRECANCEROUS 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 tobacco-associated 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 City1 International Agency for Research on Cancer Silvia Franceschi

Gary CliffordJean-Damien Combes Massimo Tommasino

Lyon

2 Service d'ORL et Chirurgie Cervico-FacialeHôpital Tenon (AP-HP) and Université Pierre et Marie Curie (UFR)

Jean Lacau St GuilySophie PerieIsabelle Brocheriou Marine LefevreRoger LacavePatrick Soussan

Paris

3 INSERM UMRS-903 CHU Reims, Hôpital Maison BlancheLaboratoire Pol Bouin : Histologie – Cytologie

Christine ClavelPhilippe 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.

Specimen collection

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

Main activities of the consortium

Benign tonsils (exfoliated cells and frozen tissue)

Age group Pediatric Young adults Older adults

Age (years) <4 5-14 15-24 25-34 35-45 >45

Sample size 100 100 100 100 100 200

Plus 50 tonsillar carcinomas to assess severe dysplasia adjacent to cancer

• 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 high-risk groups (HPV-pos and heavy smokers ≥35 yrs)

• Characterization of possible differences between HPV-positive and HPV-negative precancerous lesions

Outcome of the SPLIT study

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

1(Co) International Agency for Research on Cancer (IARC)

M. TommasinoR. SankaranarayananP. BrennanD. FormanM. Mendy

France

2 Deutsches Krebsforschungszentrum (DKFZ) M. Pawlita Germany

3 Fundació Privada Institut D'Investigació Biomedica de Bellvitge (IDIBELL)FX. BoschX. CastellsaguéL. Alemany Vilches

Spain

4 University of Antwerp (UA)M. ArbynM. PeetersJP.Bogers

Belgium

5 Istituto Europeo di Oncologia (IEO) F. ChiesaS. 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

Specimen collection Laboratory analyses Epidemiological studies Training and transfer of technology

WP2, 5

Main activities of the consortium

• 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

• HPV genotyping

• Expression of viral oncogenes (E6 and E7)

• Immuohistochemicalanalyses

• MicroRNA expression in HPV-positive and HPV-negative HNCs

• HPV serology

• HPV-positivity at different anatomical sites and geographical regions

• Trend of HPV positive cancers in the last decades

• Interaction of HPV infection and other risk factors

• Link between HPV positivity and favourable prognosis of HNC

• HPV genotyping platforms in India

• Summer school on oncogenic viruses

• Mini-symposium on HPV-associated cancers

WP3, 5, 6 WP1,4 WP7

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?

Dr Isabelle Romieu

Nutrition and Metabolism NME

Nutrition and Metabolism SectionSection Head: Dr Isabelle Romieu

Dietary Exposure AssessmentHead: Nadia Slimani, PhD

Implement international dietary methodology and study dietary exposure in developed and in transition countries

Biomarkers Head: Augustin Scalbert, PhD

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 PremenopausalBreast Cancer in Latin American Women

Multicenter population based case-control study

• Breast cancer is a leading cause of deathin Latin America

• Large number of incident cases among premenopausal women

• Little information on breast cancer phenotypes and specific risk factor

• Limited data suggest more aggressivetypes 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• Fibers• Polyphenols

• Fruits and vegetables• Meats• Dietary pattern

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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

A comprehensive databaseon polyphenols

and their metabolites

Mass spectrometry-based methodsto characterize

the polyphenol metabolome

Improved assessment of exposureto polyphenols in EPIC

375 polyphenol metabolites

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

– 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?

2p21: EPAS1 (HIF-2α)– key gene in VHL-HIF pathway– interaction with smoking

11q13: gene unknown

12q24: SCARB1– further replication needed– mediates cholesterol uptake

MP Purdue, M Johansson, D Zelenika, JR Toro, G Scelo, LE Moore, et al.

Lung cancer geneticsCurrent initiative• Part of an NCI U19 grant for transdisci-

plinary 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

CDKN2B

BAT3‐MSH5

CHRNA5‐CHRNA3‐CHRNB4

TERT‐CLPTM1L

RAD52

Future plans1. 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)

– 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?

Johansson M, Relton C, Ueland PM et al. 2010

Genetics of Head and Neck cancers

et al.

rs Chr GeneOR Pts

rs1229984 4q23 ADH1b 0.62 5x10-21

rs1573496 4q23 ADH7 0.75 5x10-17

rs698 4q23 ADH1c 1.12 3x10-7

rs4767364 12q24 ALDH2 1.13 7x10-8

rs1494961 4q21 HEL308 1.12 2x10-8

Combined

8,600 H&N cancer cases and 16,000 controlsFive variants/Three loci achieved p < 5x10-7 Future plans:

– Whole-exome sequencing of 50 tumour-germline DNA pairs (using IARC newly acquired platform)

– Focus on oropharyngeal cases

– By HPV tumour DNA status (testing ongoing)

– Parallel study with INCA Brazil

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 biorepositoriesSummary• Representative of many countries, and with harmonized collection protocols• Extensive collection (blood, slides, frozen tumours, and more recently non-tumour target organ tissue samples)• Comprehensive annotations of samples: pathological review data, clinical data, but also survival and lifestyle data

Main collectionsTarget organs From case-control studies

(existing and ongoing)From cohort prediagnosis samples

(planned)

Kidney N=2000 cases (+ corresponding controls)1000 with tumour samples400 with tumour-normal tissue pairsRussia and central Europe

N=1000 cases (+ corresponding controls)All with germline DNA and serum/plasmaWestern Europe, US, and Australia

Lung N=5000 cases (+ corresponding controls)800 with tumour samples200 with tumour-normal tissue pairsRussia and central Europe

N=5000 cases (+ corresponding controls) All with germline DNA and serum/plasmaWestern Europe, US, Australia, and Asia

Head and Neck

N=3000 cases (+ corresponding controls)1200 with tumour samplesEurope and Latin America

Future plans for N=2000 casesAll with germline DNA and serum/plasmaWestern 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, inaddition 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

Dr R. Herrero

Quality Assurance Group

Dr L. von Karsa

Screening Group

Dr R. Sankaranarayanan

Prevention and Implementation Group

Eradication of Helicobacter pylorito 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 Harms• Stomach cancer control• Peptic ulcer reduction• Dyspepsia reduction• Better nutritional status• Fewer healthcare visits

• 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, TetracyclinMetronidazole, 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 trialExposures/Subgroups Outcomes

• Age• Sex• Region• Biomarkers• Precursor lesions• Treatment

• 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 (adenoma-carcinoma 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

• Advanced adenoma:• Size: >10mm• Morphology: tubulovillous or

villous• Pathology: high grade dysplasia

Women

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 cost-effectiveness:

• 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

107 are carcinogenic to humans (Group 1)61 are probably carcinogenic to humans (Group 2A)

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 cancer-preventive 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 HBsexisted in parallel for the past 15 years.

History of IARC Cancer Prevention HandbooksIARC Sc Pub #139 Principles of Chemoprevention (Nov 1995)Preventive AgentsVol 1 NSAIDs Vol 2 CarotenoidsVol 3 Vitamin AVol 4 RetinoidsVol 5 SunscreensVol 6 Weight Control & Physical ActivityVol 8 Fruit and VegetablesVol 9 Cruciferous Vegetables,Isothiocyanates and Indoles

ScreeningVol 7 Breast Cancer Screening (Working procedures)Vol 10 Cervix Cancer Screening

Tobacco ControlVol 11 Reversal of Risk after Quitting SmokingVol 12 Methods for Evaluating Tobacco Control PoliciesVol 13 Evaluating the Effectiveness of Smoke-free PoliciesVol 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 evaluationsPreventive AgentsNSAIDs (Aspirin)Weight Control & Physical ActivityFruits and Vegetables, Vitamin B(6), Vitamin D

Screening (new modalities, cultural context, LMIC)Breast Cancer ScreeningCervix Cancer ScreeningColorectal cancerLung cancer Prostate cancerOral 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 cancerb) Effectiveness of screening for colorectal cancerc) 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?