Slide 1

Report
Global cancer control: an interdisciplinary
approach to prevention
Dr Christopher P Wild PhD
Director
International Agency for Research on Cancer
Lyon, France
Describing
occurrence
Supporting
implementation
Establishing
causes
Evaluating
prevention
Global cancer control: an interdisciplinary
approach to prevention
• The scale of the cancer problem
• Implementing what we know
• Addressing what we don’t know
Premature deaths (ages 30 to 69 years) from
cancer and other NCDs in 2011
Cancer: 15.8%
Total: 1.46 million
Cancer: 30.2%
Total: 13.82 million
Cancer: 17.0%
Total: 20.45 million
Extracted from WHO Global Health Observatory Data Repository
Global cancer burden – incidence, mortality
and prevalence (2012)
Mortality
8.2
Incidence
14.1
Prevalence
32.5
0
10
20
30
40
Million
Globally 1 in 5 men and 1 in 6 women will develop cancer before the age of 75 years
…. and 1 in 8 men and 1 in 12 women will die from the disease
Source: GLOBOCAN 2012
http://globocan.iarc.fr
Global Burden of Cancer (2012)
Incidence: 14.1 million new cases worldwide (both sexes)
(6.1 in more developed regions, 8.0 in less developed regions)
1,825,000, 13.0%
1,677,000, 11.9%
352,000, 2.5%
1,361,000, 9.7%
385,000, 2.7%
430,000, 3.1%
456,000, 3.2%
528,000, 3.7%
1,112,000, 7.9%
782,000, 5.6%
952,000, 6.8%
Lung
Breast
Colorectum
Prostate
Stomach
Liver
Cervix uteri
Oesophagus
Bladder
Non-Hodgkin lymphoma
Leukaemia
Other
Source: GLOBOCAN 2012
http://globocan.iarc.fr
Global Burden of Cancer (2012)
Mortality: 8.2 million deaths worldwide (both sexes)
(2.9 in more developed regions, 5.3 in less developed regions)
1,590,000
19.4%
745,000
9.1%
200,000
2.4%
265,000
3.2%
266,000
3.2%
307,000
3.7%
330,000
4.0%
723,000
8.8%
400,000 522,000
4.9%
6.4%
694,000
8.5%
Lung
Liver
Stomach
Colorectum
Breast
Oesophagus
Pancreas
Prostate
Cervix uteri
Leukaemia
Non-Hodgkin-Lymphoma
Other
Source: GLOBOCAN 2012
http://globocan.iarc.fr
Where does the burden fall – geography?
Incidence
Mortality
57% of cancer cases and 65% of cancer deaths
occur in less developed regions of the world
Where does the burden fall – development?
HDI>0.81
0.71 ≤ HDI<0.81
0.54≤HDI<0.71
HDI<0.54
1.0 billion
0.9 billion
4.4 billion
0.4 billion
Rates of Disability Adjusted Life Years
by HDI
Globally in 2008 168.1 million years of healthy life were lost, the majority
(>90%) years of life lost (YLLs) rather than years living with disability (YLDs)
3000
per 100,000
2500
2000
DALY's
1500
YLL
YLD
1000
500
0
Very High
High
Medium
Low
Soerjomataram I, et al. Disability-adjusted life years: country-specific
estimates for 27 cancers in 12 world regions. Lancet 380: 1840-1850 (2012).
Cancer: a global Men
but not uniform
problem
Breast cancer:
25% of all female cancers;
20% of all cancer survivors
Women
Five most frequent forms of cancer in 2012 by HDI
Source: GLOBOCAN 2012, UNDP.
Breast cancer (female): estimated incidence and
mortality rates by region
Source: GLOBOCAN 2012
http://globocan.iarc.fr
Projected global cancer incidence and
mortality burden
Millions cases per annum
2012
2025
2030
Incidence
14.1
19.3
21.7
Mortality
8.2
11.4
13.0
http://globocan.iarc.fr
Where will the burden fall – development?
% Increase 2008-2030
Very high HDI
High HDI
Medium HDI
Low HDI
0
1
2
3
4
5
2008
6
7
2030
8
9
10
11
million
new cases
Assuming no change in underlying incidence
Bray F et al. Global cancer transitions according to the Human Development
Index (2008-2030): a population based study. Lancet Oncol 2012; 13:790-801
Cancer rates are changing over time and by
development: breast and cervix by HDI
Age-standardised rates per 100,000, CIV vol. 10
Cancer rates are changing over time and by
development: colorectal cancer by HDI
Age-standardised rates per 100,000
Cancer transitions by HDI index
(2008-2030)
• High and Very high HDI: breast, lung, colorectum
and prostate most common
• Medium HDI: oesophagus, stomach and liver
cancers also common
• Low HDI: cervical cancer more common than
breast and liver
• Medium and high HDI: decreases in cervical and
stomach cancer incidence offset by increases in
breast, prostate and colorectum
Bray F et al. Global cancer transitions according to the
Human Development Index (2008-2030): a population
based study. Lancet Oncol 2012; 13:790-801
“We cannot treat our way out of
the cancer problem”
A balanced and integrated approach to
prevention and treatment is required
Global cancer control: an interdisciplinary
approach to prevention
• The scale of the cancer problem
• Implementing what we know
• Addressing what we don’t know
Primary cancer prevention
• Around half of cancers could be prevented
by applying the knowledge we have;
• The majority of cancers have a lifestyle or
environmental cause, so the potential for
prevention is much higher
Vineis P and Wild CP (2014) The Lancet, 383: 549-557
IARC Monographs Volume 100
Major cancer risk factors globally
Risk Factor
Comments
Tobacco
Implement WHO Framework Convention on Tobacco
Control; taxation; bans on advertising; regulations on
smoking in public places; counter the introduction into
low and middle-income countries
Infections
HBV and HPV vaccination; H. pylori eradication (?);
Avoid contaminated injections; treatment of HBV and
HCV chronic carriers
Alcohol
Avoid harmful use of alcohol; increase awareness;
taxation and regulation
Physical inactivity,
overweight and obesity
Increase physical activity and improve weight control;
major area where research is needed
Major cancer risk factors globally
Risk Factor
Comments
Radiation
Avoid excessive sun exposure and indoor tanning;
avoid excessive use in medical diagnosis, including
in children; awareness and remediation of indoor
radon levels
Environmental carcinogens
Naturally occurring (arsenic, aflatoxins); air
pollution: regulatory and other control measures
Occupations
Occupational health; counter risks of “exporting”
at-risk occupational exposures to low and middleincome countries
Reproductive factors and
hormones
Allied to earlier age at menarche, later age at first
live birth; fewer children; shorter duration of
breast feeding
Regional variation in cancer risk factors:
infection related cancers
Opportunities for early detection and
treatment
• Breast cancer*: population-based screening;
mammography, clinical breast examination;
breast awareness
• Cervical cancer: cytology; HPV DNA testing;
visual inspection with acetic acid; c
• Colorectal cancer: population-based screening;
FOBT, sigmoidoscopy, colonoscopy
• Oral cancer: in high incidence regions (e.g. east Asia)
*IARC Handbook on Cancer Prevention vol. 15
Nov 2014; supported by INCa, France
Prevention works but takes time
– lung and cervix
Lung, men
Cervix uteri
Prevention works but takes time
– HPV vaccination
Van de Velde et al., J. Natl. Cancer Inst., 104: 1712-22
Global cancer control: an interdisciplinary
approach to prevention
• The scale of the cancer problem
• Implementing what we know
• Addressing what we don’t know
Cancers where aetiology is (largely)
unknown
Organ sites
Prostate
Estimated annual no. Percent global
new cases worldwide cancer burden
1,100,000
7.9
Lymphoma and
Leukemia
Kidney
850,000
6.0
340,000
2.4
Pancreas
340,000
2.4
Thyroid
300,000
2.1
Brain
260,000
1.8
1,400,000
9.7
Colorectal
Two-way Translational Cancer Research
Basic Science
Population
Causes and
Prevention
Risk factors
Patient
Personalized
treatment
Specific molecular
alterations
Prognosis
Laboratory Methodologies
genomics, transcriptomics, epigenomics, proteomics, metabolomics
Wild CP (2012) Int. J. Epidemiol, 41: 24-32
Wild CP et al., (2013) Env. Molec. Mutagen.54: 480-499
Temporal application of exposure biomarkers in
cancer epidemiology
Exposure
Peri-natal Adolescence
Childhood
Birth cohort
Timing of
exposure
measurement
Disease
Adult
Adult cohort
Case-control
study
Carcinogen metabolites Mutation spectra
DNA/protein adducts
Antibodies
Cytogenetic alterations
Laboratory science in population
studies – five areas of promise
Improved exposure assessment
Contributing to biological plausibility
Stratifying risks by tumour sub-group
Evaluating interventions
Hazard and risk assessment
Importance of environmental and
lifestyle exposure assessment
• Most common chronic diseases have an
environmental or lifestyle aetiology
• Currently exposure measurement is problematic
in many areas, leading to misclassification
• Value of prospective cohort studies (e.g. UK
Biobank) are predicated on the availability of
accurate exposure assessment
• The requirement for an “exposome” to
complement the genome (see Wild CP (2005) CEBP14:
1847-1850; Wild CP (2012) Int. J. Epi, 41: 24-32)
Technological advances applicable to
epidemiology
Biomarkers (omics) –
general or targeted
Transcriptomics, Proteomics,
Metabolomics, Epigenomics,
Adductomics, Lipidomics
Sensor technologies
(including mobile phones)
Environmental pollutants, physical
activity, stress, circadian rhythms,
location (global positioning systems
(GPS))
Imaging (including
mobile phones, video
cameras)
Diet, environment, social interactions
Electronic diaries, palm Behaviour and experiences
(ecological momentary assessment),
top computers
stress, diet, physical activity
Exposure – clues from transcriptomics
A: Probe sets comparing smokers and nonsmokers:
Top right: higher expression in smokers; Top left:
lower expression in smokers
A >1; down-regulated in
B: Up-regulated in smokers
smokers <1 compared to nonsmokers
C: Expressed above average in red, below in blue;
each row is one of 375 smoking-responsive genes
Tilley et al., PLoS ONE 6: July 2011
Exposure – clues from methylomics
Methylation of specific
gene promoter regions by:
Tumour grade
Risk factor
Hernandez Vargas et al., PLoS One 2010
Hy d ro x y p h e n y l a c e ti c _ a c i d _ s u l fa te _ (9 0 7 0 )
Va n i l l o y l g l y c i n e _ (7 7 9 5 )
Ph e n a c e ty l g l y c i n e _ (5 1 0 )
g a l l i c _ a c i d _ (8 1 6 4 )
Di h y d ro x y b e n z o i c a c i d _ (7 1 0 3 )
(+)-Ca te c h i n _ (6 0 7 2 )
g e n ti s i c _ a c i d _ s u l fa te _ (4 3 3 5 )
h o m o v a n i l l i c _ a c i d _ s u l fa te _ (8 8 3 )
Hy d ro x y p ro l i n e _ (1 5 7 )
3 -Hy d ro x y -3 -(3 -m e th o x y -4 -h y d ro x y p h e n y l )p ro p i o n i c a c i d _ g l u c u ro n i d e _ (5 7 2 2 )
Di h y d ro re s v e ra tro l _ g l u c u ro n i d e _ (2 6 4 4 )
3 -O-M e th y l c a te c h i n _ _ s u l fa te _ (2 4 5 3 )
3 -Hy d ro x y b e n z o i c a c i d _ (6 6 6 5 )
2 -Hy d ro x y h i p p u ri c _ a c i d _ (6 6 1 4 )
Ga l l i c _ a c i d _ e th y l _ e s te r_ g l u c u ro n i d e /3 _ 4 -O-Di m e th y l g a l l i c _ a c i d _ g l u c u ro n i d e _ (5 2 7 7 )
L -g l y c y l -L -h y d ro x y p ro l i n e _ (4 6 2 )
Na ri n g e n i n _ (1 3 1 2 )/(AFM U [M +FA-H]/c a te c h i n [M -H2 O-H])
L -g l y c y l -L -h y d ro x y p ro l i n e _ (4 6 1 )
m -Co u m a ri c _ a c i d _ s u l fa te _ (1 0 1 2 )
4 -Hy d ro x y h i p p u ri c _ a c i d _ (6 6 1 2 )
(+)-Ca te c h i n _ s u l fa te _ (7 6 9 1 )
(-)-Ep i c a te c h i n _ s u l fa te _ (4 7 4 8 )
4 -O-M e th y l c a te c h i n _ _ s u l fa te _ (2 4 5 2 )
Ep i c a te c h i n 7 -O-g l u c u ro n i d e _ _ s u l fa te _ (3 4 2 0 )
3 ,5 -Di h y d ro x y b e n z o i c a c i d _ (2 4 5 )
4 -O-m e th y l g a l l i c _ a c i d _ s u l fa te _ (7 5 1 1 )
4 -O-m e th y l g a l l i c _ a c i d _ (4 1 4 )
g a l l i c _ a c i d _ (6 5 3 5 )
3 -Hy d ro x y p h e n y l v a l e ri c _ a c i d _ g l u c u ro n i d e _ (2 3 4 5 )
5 -(3 _ 4 _ 5 -tri h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ s u l fa te _ (4 3 8 7 )
5 -(3 _ 5 -d i h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ 3 -O-g l u c u ro n i d e _ (4 4 9 4 )
4 -O-M e th y l e p i g a l l o c a te c h i n 3 -O-g a l l a te _ (4 9 4 4 )
4 -Hy d ro x y -(3 _ 4 -d i h y d ro x y p h e n y l )v a l e ri c _ a c i d _ (8 2 1 )
Ep i c a te c h i n 3 -O-g l u c u ro n i d e _ (3 0 5 3 )
Pro to c a te c h u i c a l d e h y d e _ (5 4 5 3 )
s i n a p i c _ a c i d _ s u l fa te _ (1 6 6 8 )
Ho m o v a n i l l i c a c i d /Di h y d ro c a ffe i c a c i d /3 -Hy d ro x y -3 -(3 -h y d ro x y p h e n y l )p ro p i o n i c a c i d _ (4 0 3 )
Na ri n g e n i n _ (8 0 3 3 )
Na ri n g e n i n 4 -O-g l u c u ro n i d e _ (2 9 5 1 )
(-)-Ep i g a l l o c a te c h i n _ g l u c u ro n i d e _ (5 0 2 0 )
Va n i l l o y l g l y c i n e _ (6 7 9 3 )
u n k n o wn _ (v a n i l l o y l g l y c i n e _ s u l fa te )_ (8 8 2 9 )
Pro l y l h y d ro x y p ro l i n e _ (8 4 2 )
d i h y d ro x y b e n z o i c _ a c i d _ s u l fa te (6 3 1 8 )
He s p e re ti n _ 3 -s u l fa te _ (2 4 3 4 )
He s p e re ti n _ 3 -g l u c u ro n i d e _ (3 1 1 7 )
2 -Hy d ro x y p h e n y l a c e ti c _ a c i d _ s u l fa te _ (8 8 4 )
o -Co u m a ri c _ a c i d _ s u l fa te _ (5 2 3 2 )
4 -O-M e th y l e p i g a l l o c a te c h i n 3 -O-g a l l a te _ (3 0 9 5 )
Gl y c y l p ro l y l h y d ro x y p ro l i n e _ (1 4 6 6 )
2 -Hy d ro x y b e n z o i c a c i d _ (6 3 0 8 )
(-)-Ep i g a l l o c a te c h i n _ s u l fa te _ (5 0 9 1 )
(-)-Ep i g a l l o c a te c h i n _ 3 -O-g l u c u ro n i d e _ (3 1 4 1 )
Va n i l l o y l g l y c i n e _ g l u c u ro n i d e _ (5 8 9 3 )
3 -Hy d ro x y -3 -(3 -m e th o x y -4 -h y d ro x y p h e n y l )p ro p i o n i c a c i d _ (6 7 8 )
5 -p -Co u m a ro y l q u i n i c a c i d /5 -(3 _ 5 -d i h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ 3 -O-g l u c u ro n i d e _ (2 4 5 4 )
L -a l p h a -g l u ta m y l -L -h y d ro x y p ro l i n e _ (1 1 7 8 )
Pro to c a te c h u i c _ a c i d _ s u l fa te _ (9 0 7 )
3 -c a ffe o y l q u i n i c _ a c i d _ (3 9 6 7 )/Di h y d ro fe ru l i c a c i d 4 -O-g l u c u ro n i d e [M -H2 O-H]
4 -Hy d ro x y b e n z o i c a c i d _ (8 2 6 7 )
5 -(3 _ 4 _ 5 -tri h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ g l u c u ro n i d e _ (5 0 2 1 )
Co u m a ri c _ a c i d _ s u l fa te _ (1 0 1 3 )
Ph e n a c e ty l g l y c i n e _ (5 0 9 )
5 -(3 -M e th o x y -4 -h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ 4 -O-g l u c u ro n i d e _ (2 5 8 6 )
Va n i l l i c a c i d /3 ,4 -Di h y d ro x y p h e n y l a c e ti c a c i d /4 -Hy d ro x y m a n d e l i c a c i d _ (3 2 3 )
Re s v e ra tro l _ 3 -O-g l u c u ro n i d e _ (2 6 2 9 )
Re s v e ra tro l _ 3 -O-g l u c u ro n i d e _ (8 2 7 0 )
Pro l y l h y d ro x y p ro l i n e _ (3 9 2 7 )
Hy d ro x y p ro l i n e _ (1 5 8 )
Va n i l l o y l g l y c i n e _ g l u c u ro n i d e _ (2 6 0 4 )
3 -O-M e th y l -(-)-e p i c a te c h i n _ 3 -O-g a l l a te _ s u l fa te _ (6 2 1 8 )
4 -e th y l b e n z o i c _ a c i d _ g l u c u ro n i d e _ (5 8 2 3 )/ty ro s o l _ g l u c u ro n i d e
(-)-Ep i g a l l o c a te c h i n _ g l u c u ro n i d e _ (5 0 2 0 )
m e th y l g a l l i c _ a c i d _ (4 1 2 )/(h y d ro x y b e n z o i c _ a c i d [M +FA-H])
u n k n o wn _ d i h y d ro x y b e n z o i c _ a c i d _ s u l fa te _ (8 4 5 0 )
(-)-Ep i g a l l o c a te c h i n 3 -O-g a l l a te _ (3 0 0 9 )
g a l l i c _ a c i d _ (3 3 7 )
L -a l p h a -g l u ta m y l -L -h y d ro x y p ro l i n e _ (5 4 9 2 )
Ca ffe i c _ a c i d _ 3 -O-g l u c u ro n i d e _ (8 1 2 9 )
Va n i l l i c a c i d /3 ,4 -Di h y d ro x y p h e n y l a c e ti c a c i d /4 -Hy d ro x y m a n d e l i c a c i d _ (3 2 4 )
e _ (2 6 1 7 )/((3 -(4 -h y d ro x y -3 ,5 -d i m e th o x y p h e n y l )-p ro p i o n i c a c i d )/c a ffe o y l q u i n i c _ a c i d [M +FA-H]
Ph l o re ti n _ 2 -O-g l u c u ro n i d e _ (2 9 6 2 )
4 -Hy d ro x y -(3 _ 4 -d i h y d ro x y p h e n y l )v a l e ri c _ a c i d _ (5 6 1 0 )
3 -Hy d ro x y h i p p u ri c _ a c i d _ (4 7 8 8 )
Di h y d ro i s o fe ru l i c _ a c i d _ 3 -O-g l u c u ro n i d e _ (5 0 5 9 )
Ph l o ri n (a g l y c o n e p h l o ro g l u c i n o l )(6 1 8 3 )
3 -O-m e th y l g a l l i c _ a c i d _ s u l fa te _ (8 1 8 3 )
3 -Hy d ro x y -3 -(3 -m e th o x y -4 -h y d ro x y p h e n y l )p ro p i o n i c a c i d _ (6 7 5 )
Ep i c a te c h i n 7 -O-g l u c u ro n i d e _ (4 9 4 5 )
5 -Fe ru l o y l q u i n i c _ a c i d _ s u l fa te _ (4 9 2 3 )
Na ri n g e n i n _ (1 3 0 9 )/(AFM U [M +FA-H]/c a te c h i n [M -H2 O-H])
Hy d ro x y p ro l i n e _ (1 5 6 )
3 ,4 -Di h y d ro x y p h e n y l l a c ti c a c i d m e th y l e s te r_ (6 7 6 )
p -Co u m a ri c _ a c i d _ s u l fa te _ (1 0 1 1 )
Fe ru l i c _ a c i d _ 4 -s u l fa te _ (7 2 3 6 )
4 -Hy d ro x y p h e n y l a c e ti c _ a c i d _ s u l fa te _ (8 8 2 )
5 -c a ffe o y l q u i n i c _ a c i d _ s u l fa te _ (2 8 6 2 )
3 -Hy d ro x y p h e n y l a c e ti c _ a c i d _ s u l fa te _ (4 5 3 1 )
4 -Fe ru l o y l q u i n i c _ a c i d _ (5 3 8 1 )
c a ffe i c a c i d e th y l e s te r_ s u l fa te _ (1 5 0 4 )
5 -c a ffe o y l q u i n i c _ a c i d _ g l u c u ro n i d e _ (3 3 5 6 )
4 -c a ffe o y l q u i n i c _
c i d _ (4 4 5 1 )
5 -c a ffe o y l q u i n i c _ a c i d _ (4 1 9 5 )
3 -Ph e n y l p ro p i o n i c _ a c i d _ g l u c u ro n i d e _ (1 8 8 2 )
Ca te c h o l _ g l u c u ro n i d e _ (1 4 7 3 )
5 -Fe ru l o y l q u i n i c _ a c i d _ (2 3 2 1 )
Ca ffe i c _ a c i d _ 3 -s u l fa te _ (4 7 7 0 )
a ro y l q u i n i c a c i d [M +FA-H]/5 -(3 _ 5 -d i h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ 3 -O-g l u c u ro n i d e _ (4 5 1 1 )
a ro y l q u i n i c a c i d [M +FA-H]/5 -(3 _ 5 -d i h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ 3 -O-g l u c u ro n i d e _ (4 5 1 1 )
3 -O-m e th y l g a l l i c _ a c i d _ (4 1 5 )
Ca ffe i c _ a c i d _ 4 -s u l fa te _ (4 2 0 6 )
3 -M e th o x y -4 -h y d ro x y p h e n y l l a c ti c a c i d _ (6 7 9 )
Ca te c h o l _ (9 7 4 8 )
(-)-Ep i g a l l o c a te c h i n _ g l u c u ro n i d e _ (5 0 2 0 )
Fe ru l i c _ a c i d _ 3 -s u l fa te _ (1 3 4 0 )
3 -M e th o x y -4 -h y d ro x y p h e n y l v a l e ro l a c to n e _ 4 -O-s u l fa te _ (1 6 5 3 )
5 -(3 _ 4 _ -d i h y d ro x y p h e n y l )-v a l e ro l a c to n e _ s u l fa te _ (1 4 9 7 )
4 -Hy d ro x y -(3 _ 4 -d i h y d ro x y p h e n y l )v a l e ri c _ a c i d _ _ g l u c u ro n i d e _ (2 6 1 5 )
3 -M e th o x y -4 -h y d ro x y p h e n y l v a l e ro l a c to n e _ 4 -O-s u l fa te _ (8 0 5 0 )
4 -Hy d ro x y -(3 _ 4 -d i h y d ro x y p h e n y l )v a l e ri c _ a c i d _ _ s u l fa te _ (1 6 8 9 )
3 -Fe ru l o y l q u i n i c _ a c i d _ (5 0 9 2 )
5 -Hy d ro x y p h e n y l -g -v a l e ro l a c to n e _ _ s u l fa te _ (1 3 0 5 )
i n i c a c i d [M +Ha c -H]/5 -(3 -M e th o x y -4 -h y d ro x y p h e n y l )-g -v a l e ro l a c to n e _ 4 -O-g l u c u ro n i d e _ (5 4 4 2 )
Exposure - clues from metabolomics
Urinary polyphenols in
high and low consumers
within the EPIC study
Coffee_24DR
Coffee_FFQ
Red.wine_24DR
Red.wine_FFQ
Citrus.fruits_24DR
Citrus.fruits_FFQ
Apple.and.pear_24DR
Apple.and.pear_FFQ
Tea_24DR
Tea_FFQ
Chocolate..candy.bars..paste..confetti_24DR
Chocolate..candy.bars..paste..confetti_FFQ
Edmands W, Scalbert A
IARC, unpublished
Laboratory science in population
studies – what is promised?
Improved exposure assessment
Contributing to biological plausibility
Stratifying risks by tumour sub-group
Evaluating interventions
Hazard and risk assessment
Kinetics of N2-ethylidene-DNA adducts in the
oral cavity after drinking alcohol
• Subjects consumed
approx. 27 (d1), 39
(d2) or 51 (d3) g
ethanol; provided oral
mouthwash for DNA
extraction
• Dose response with
peak adduct after 4
hours; up to 100-fold
above baseline
• Considerable interindividual variation
Balbo S et al. Cancer Epidemiol Biomarkers Prev
2012; 21:601-608
©2012 by American Association for Cancer Research
Laboratory science in population
studies – what is promised?
Improved exposure assessment
Contributing to biological plausibility
Stratifying risks by tumour sub-group
Evaluating interventions
Hazard and risk assessment
Genomic and transcriptomic architecture of
breast tumours
• Analysis of acquired somatic copy number
aberrations and gene expression in 2,000 tumours
• Identified novel molecular sub-groups of breast
cancers with distinct clinical outcomes
• Subgroup-specific gene networks associated with
aberration hotspots
• A basis for stratified medicine (beyond Herceptin)
• But any implications for breast cancer aetiology?
Curtis et al., Nature 2012
Molecular subtypes of premenopausal breast
cancer in Latin American Women
• Standardized protocol for clinical,
pathological information and biological
specimens
• Identification of specific endogenous
(genetics and genomics) and
exogenous factors (biological
modifications, behavioral, dietary and
cultural factors) with specific subtypes
of premenopausal BC, identified
based on molecular and pathological
phenotypes
• Provide advanced training,
development of the BC research
community in Latin America, and
influence the public health agenda
regarding the management of BC
IARC PI: Dr Isabelle Romieu, Section of
Nutrition and Metabolism, IARC
Laboratory science in population
studies – what is promised?
Improved exposure assessment
Contributing to biological plausibility
Stratifying risks by tumour sub-group
Evaluating interventions
Hazard and risk assessment
Aflatoxins and human health
Widespread exposure
through contamination of
staple foods (cereals and
nuts):
•
•
•
•
Aflatoxicosis
Liver cancer
Growth impairment
Immune modulation?
Exposure to aflatoxin associated with
impaired growth
AF-alb (pg/mg)
80
Z >0
Z 0 to-2
Z -2 to -3
Z <=-3
60
40
20
0
Height for Age
Weight for Age
Growth Status (Z score)
Mean height increase (cm)
Longitudinal study of aflatoxin exposure
and child growth in Benin
6
5
4
3
2
1
0
Lower
Mid-lower
Mid-upper
Upper
Quartile of AF-alb adducts over 8 months
200 children, aged 16-37 months followed over 8 months
Adjusted for age, height, weaning status, mothers SES and
village
Biomarkers and intervention studies –
aflatoxin in subsistence farms in Guinea
20 Villages (10 intervention, 10 control), 30 subjects per village
Sept/Oct
Dec/Jan
Intermediate
Survey 1
Survey 1
Feb/Mar
Intermediate
Survey 2
Survey 2
Blood sample collection
Survey 3
Groundnut sample collection
Mean levels of AF-alb are reduced in
individuals following intervention
24
mean AF-alb (pg/mg)
intervention
control
20
16
12
8
4
0
1
2
3
survey points
Turner et al., (2005) The Lancet, 365, 1950-1956
percent non-detectable AF-alb
Intervention increases the number of
individuals with non-detectable blood AF-alb
40%
intervention
control
30%
20%
10%
0%
1
2
3
survey points
Turner et al., (2005) The Lancet, 365, 1950-1956
Implementation or operational
cancer research
- a neglected area
The Thailand Colorectal Cancer Screening (CRC) Pilot Demonstration Project
in Lampang Province
Goals
• Evaluate the acceptability, feasibility,
organization, implementation, monitoring
and evaluation of colorectal cancer
screening in the general population in
Thailand by integrating the programme into
the existing public health services
BURMA
LAOS PDR
Lampang
Province
THAILAND
Bangkok
• Inform and guide the eventual scaling up of
CRC screening to cover the entire country
CAMBODIA
In collaboration with the:
VIETNAM
Gulf of
Thailand
National Cancer Institute Thailand
Andaman
Sea
Map showing Lampang Province, Thailand
The Thailand Colorectal Cancer Screening (CRC)
Pilot Demonstration Project in Lampang Province (2011-2012)
Invited to participate
(50 to 65 years)
n = 127,301
Completed faecal
occult blood testing
n = 80,012 (63%)
Participated
n = 80,012 (63%)
iFOBT negative
n = 79,139
iFOBT positive
n = 873 (1.1%)
Colonoscopy
n = 627 (72%)
Adenoma
n = 187
(Advanced adenoma (n = 75))
Colorectal cancer
n = 23
Stage I = 2
Stage II = 12
Stage III = 7
Unknown = 2
Khuhaprema et al, BMJ Open 2014;4:e003671
Gambia Hepatitis Intervention Study –
randomized trial of HBV vaccine
• Evaluation of the HBV vaccine to prevent liver
disease and liver cancer
• Begun in mid-1980s including ~120,000
children – expected results in next 5-10 years
• Identification of cases through the Gambian
National Cancer Registry
•Collaboration between IARC, MRC UK and
The Gambian Government
Impact of routine EPI on chronic
HBV infection in The Gambia
Age
HBsAg-
HBsAg+
Percentage
Total
1.0-4.9
1,918
3
0.2
1,921
5.0-9.9
1,585
6
0.4
1,591
10.0-14.9
815
10
1.2
825
15.0-18.5
271
5
1.8
276
Total
4,589
24
0.5
4,613
Peto TJ, Mendy M., Lowe Y., Webb EL., Whittle HC
and Hall AJ (2014) BMC Infectious Diseases 14: 7
Conclusions
• The challenge of a rising cancer burden must be
met by an integrated approach of prevention,
early detection and treatment
• Recent advances in the molecular (epi)genetics of
cancer and related tools offer exciting interdisciplinary approaches to cancer prevention
• Implementation research into how prevention
measures may best be integrated into health
services settings is crucial
We have a duty of care to the patients of
today and to the populations of tomorrow

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