Current Scientific Initiatives Mechanisms of Carcinogenesis Section (MCA) Zdenko Herceg, PhD

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
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7000
6500
6000
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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
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?