Cancer
Epidemiology and Prevention
Outline
Descriptive epidemiology
Risk factors and prevention
Cause of cancer
Manami Inoue, M.D., PhD.
Graduate School of Medicine, The University of Tokyo
Center for Public Health Sciences, National Cancer Center
Cancer screening
Data source (http://www-dep.iarc.fr/)
Cancer Incidence in Five Continents
Cancer Statistics
DESCRIPTIVE EPIDEMIOLOGY
Year 1965, 1970, 1975, 1980, 1985, 1990, 1995, 2000, 2005
Publish every 5 years
Incidence
Population based cancer registry
Quality control
THE GLOBOCAN PROJECT
The latest version: GLOBOCAN 2012
Incidence, mortality, prevalence
At national level, for all countries of the world.
Cancer Incidence in the world 2012
Cancer incidence in selected countries (ASR, GLOBOCAN 2012)
Men
0
100
Women
200
300
400
500
385.3
France (metropolitan)
100
200
300
400
328.8
Denmark
Australia
373.9
USA
368.7
297.4
Norway
Korea, Republic of
Belgium
364.8
293.6
Slovenia
358.2
Hungary
356.1
Denmark
354.3
347.0
USA
Czech Republic
345.9
Ireland
343.3
Korea, Republic of
340.0
260.4
Japan
231.6
Brazil
The Netherlands
289.6
Belgium
288.9
Ireland
278.9
Australia
278.6
Canada
277.4
Norway
277.1
France (metropolitan)
276.7
218.8
Japan
China
211.2
China
92.4
186.8
Brazil
Singapore
India
198.7
Singapore
India
185.7
139.9
97.4
500
Data source
Cancer Incidence and Mortality in Japan
Mortality data
Trends in Crude Mortality Rate for Leading Causes of Death
500
Vital Statistics Japan (Ministry of Health, Labour and Welfare)
Database file available for 1958-2014
Cancer Incidence data
Database file available for 1975-2011
Monitoring of Cancer Incidence in Japan (MCIJ) Project (Japan Cancer
Surveillance Research Group)
National Cancer Registry (mandatory reporting) starts from January 1,
2016.
400
Per 100,000
200
Cancer
1981
300
Tuberculosis
Stroke
Heart Disease
100
Pneumonia
2015
2010
2005
2000
1995
1990
1985
1980
1975
1970
1965
1960
1955
Both data sources are available from Cancer Registry and Statistics. Cancer
Information Service, National Cancer Center, Japan.
(http://ganjoho.jp/public/index.html)
1950
(Vital Statistics of Japan)
10
60
Colon
Ovary
Rectum
Stomachconstant decrease
LungHighest after 1993
LiverPeaked around 1995
Increase in colon cancer and prostate cancer (popular in western population)
Women
Decline in stomach and Uterus cancer
Increase in lung, colon and breast cancer (popular in western population)
Liver cancer
Gastric cancer
Those who infected before/around World War II become cancer onset age
Prevalence of Helicobacter pylori infection decrease by birth-cohort
In general
Westernization of lifestyle and disease structure
Aging
CRC
30
20
Rectum
Liver
10
2010
Uterus
Lung
Colon
Ovary
Age-standardized mortality rate (by world population)
US men Peak
Age-Standardized Mortality Rate
Rapid spread of smoking habit after World War II
Peak 10 years behind Western populations
Lower risk of smoking habit compared with Western population
40
Time trend of lung cancer mortality
Lung cancer
Stomach
50
Men
Stomach: Top, constant decrease
High ranked: lung and prostate cancer (popular in western population)
Liver and colon cancer: plateau
Women
Breast: Top
Stomach cancer: constant decrease
Epidemiological background of cancer in Japan
60
0
2005
0
2000
Colon
Liver
Ovary
1960
1965
1970
1975
1980
1985
1990
1995
2000
2005
2010
Lung
CRC
Uterus
Rectum
1995
Stomach
Rectum
Breast
20
1990
1960
1965
1970
1975
1980
1985
1990
1995
2000
2005
2010
Colon
Liver
1985
Liver
40
1980
Uterus
Prostate
Breast
CRC
10
Men
CRC
Lung
Rectum
Prostate
Stomach
80
2010
Stomach
Colon
Breast
70
100
2005
CRC
80
120
2000
100
Liver
Cancer
Incidence
in Japan
Cancer mortality
Women
90
1995
Per 100000
Cancer incidence
Women
Per 100000
1990
Lung
140
1985
Stomach
Cancer incidence
Men
Per 100000
1980
Cancer mortality
Men
1975
100
1975
Per 100000
60
50
Japan men Peak
40
30
20
10
0
1950
1952
1954
1956
1958
1960
1962
1964
1966
1968
1970
1972
1974
1976
1978
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
2012
Cancer
mortality
in Japan
(vital staitstics)
H. pylori
Declining trends in prevalence of Helicobacter pylori
infection by birth-year in a Japanese population
Trends in smoking by birth cohorts born
between 1900 and 1977 in Japan
Prevalence (%)
100
90
80
70
60
% 50
40
30
20
10
0
1900
1910
1920
1930
1940
1950
1960
1970
1980
1990
2000
2010
Birth Year
Data source: Asaka M Gastroenterol 1992; 102:760-766. Akamatsu T et al. J Gastroenterol 2011; 46: 13531360. Ueda J et al. Helicobacter. 2014;19(2):105-10. Tamura T et al. Nagoya J Med Sci. 2012;74(1-2):63-70.
Hirayama Y et al. J Gastroenterol Hepatol 2014; 29 (suppl 4): 16-19. Okuda M, et al. Helicobacter.
2015;20(2):133-8. Watanabe M et al. Cancer Sci. 2015;106(12):1738-43.
Marugame T. Prev Med, Volume 42, Issue 2, 2006, 120127
Probability of becoming cancer (%)
Cumulative risk of cancer in Japan (2012)
70
Both sexes
60
Men
60
Women
52
50
Evidence-based Cancer Prevention
RISK FACTORS AND PREVENTION
30
19
20
10
0
1 1 2
2 2 3
4 3 5
6 5 8
-39
-44
-49
-54
9 8
10
-59
141414
-64
22
26
18
-69
34
31
49
42
42
40
39
33
27
22
-74
-79
-84
85+
Age (years)
Center for Cancer Control and Information Services, National Cancer Center, Japan
Is cancer preventable?
Why is cancer increasing?
Pesticide?
Electromagnetic fields?
Radiation?
Diesel fumes?
Food additives?
Genetic?
Environmental hormone?
400,000
Dioxin?
Number of cancer
Deaths in Japan
350,000
300,000
UV?
250,000
200,000
150,000
100,000
2010
2005
2000
1995
1990
1985
1980
1975
1970
1965
1960
1955
1950
1945
1940
1935
1930
1925
2014
Is cancer preventable?
Is cancer preventable?
Cancer incidence
Men
Per 100000
1920
1910
1915
50,000
140
Cancer Incidence among Migrants
Age-standardized incidence rate of Japanese population in various
geographic areas
Per 100000
120
Cancer incidence
Women
Per 100000
Breast
80
CRC
Lung
60
60
CRC
40
Colon
20
Rectum
(Age-standardized incidence rate by Japanese model population in 1985)
32
25 28
12
10
22
8 8
11
56
47
42
36
34
30
20
Women
46
15
5 7
19
24
18 19
18
10
7 8
0
Stomach
Colon
2010
2005
1990
1985
1980
1975
2010
2005
2000
1995
1990
1985
1980
1975
Liver
Ovary
2000
Rectum
Uterus
Lung
60
Men
40
Liver
20
General population in Brazil (Sao Paulo)
69
70
50
Stomach
1995
Colon
Jpn in Brazil (Sao Paulo)
86
60
Prostate
40
Jpn (Miyagi)
80
Stomach
80
Jpn in US (Hawaii)
88
90
100
100
US whites (Hawaii)
100
Standardized by World Population
Prostate
Stomach
Colon
Breast
Tsugane S et al, Cancer Causes Control 1990; 1:189-193.
Cancer Incidence in Five Continents Vol 4
Is cancer preventable?
Cancer is Preventable!
Agreement of cancer among twins
Concordance (%) among Monozygotic twins
What causes cancer?
100%
80%
60%
40%
20%
15
0%
Colorectum
(Male)
Colorectum
(Female)
16
20
Breast
Prostate
Concordance (%) among Dizygotic twins
100%
80%
60%
40%
20%
6
10
Colorectum
(Male)
Colorectum
(Female)
Breast
0%
Causes of cancer
Prostate
Ahlbom A et al. JNCI 1997;89:287-93
(WHO/IARC: World Cancer Report , 2003)
10 recommendations
WCRF/AICR2007
1.
BODY FATNESS: Be as lean as possible within the normal range of body weight
2.
PHYSICAL ACTIVITY: Be physically active as part of everyday life
3.
FOODS AND DRINKS THAT PROMOTE WEIGHT GAIN: Limit consumption of
energy-dense foods, Avoid sugary drinks
4.
PLANT FOODS: Eat mostly foods of plant origin
5.
ANIMAL FOODS: Limit intake of red meat and avoid processed meat
6.
ALCOHOLIC DRINKS: Limit alcoholic drinks
7.
PRESERVATION, PROCESSING, PREPARATION: Limit consumption of salt, Avoid
moldy cereals (grains) or pulses (legumes)
8.
DIETARY SUPPLEMENTS: Aim to meet nutritional needs through diet alone
9.
BREASTFEEDING (Special Recommendation): Mothers to breastfeed; children to
be breastfed
10. CANCER SURVIVORS (Special Recommendation): Follow the recommendations
for cancer prevention
Factor
1. Tobacco Smoking
2. Diet, Nutrition, and Physical Inactivity
5. Reproductive Factors and Hormones
1) Sex hormones
1) Alcohol drinking
2) OC use and HRT
2) Low fruit and vegetable intake
3) Phytoestrogen (isoflavones, lignans)
3) High salt and salt-preserved food intake
4) Processed meat and red meat
5) Physical inactivity
6) Obesity
3. Chronic infections (virus, bacteria, parasites)
4) IGF-1
6. Other factors
1) Medicinal Drugs
2) Radiation
7. Genetic sysceptibility
4. Occupational and Environmental Exposures
1) Occupation
2) Outdoor and indoor pollutions
The Second Expert Report (2007)
Food, Nutrition, Physical Activity, and the Prevention
of Cancer: a Global Perspective
30
Currently offered as Continuous Update Project (CUP)
http://epi.ncc.go.jp/en/can_prev/index.html
1.00
1.26
1.53
1.37
0.60
Bladder
3+ cups/d
Pancreas
1-2 cups/d
Women
None
0.27
1-4 d/w
0.41
0.80 0.70
Endometrium
1.70
p trend=0.042
p trend=0.007
1.30 1.30
0.61
0.55
None
1-4 d/w
0.38
3+ cups/d
0.90
0.43
1-2 cups/d
0.89
1.00 0.97
2 d/w
0.89
1.00 1.03
3-4 d/w
0.77
1.00
1+ cup/d
1.00
0.44
0.55
Liver
p trend=0.04
0.79 0.74
1.00 1.00
3+ cups/d
0.74 0.76
Colon
(Invasive)
1.00
p trend=0.04
p trend<0.001
1.00
Bladder
3+ cups/d
1.23
3-4 d/w
HR
2
1.07
1-2 cups/d
1.26
Pancreas
3-4 d/w
1.00
Liver
1-2 cups/d
Evidence
from single
population
Men
Colon
(Invasive)
Rarely
Result from single population/single study
Systematic review
Meta-analysis
Pooled analysis
HR
1-2 d/w
Evaluation of Evidence
Example: Coffee and risk of cancer JPHC Study
Rarely
1-2 d/w
Check your hepatitis virus infection status and, if infected, follow the advice of
board certified physician. Check your Helicobacter pylori infection status.
5+ cups/d
3-4 cups/d
BMI21-27
21-25
5+ cups/d
Maintain an appropriate weight during adulthood.
Middle-aged men should keep their BMI (body mass index) between 21 and 27,
and women between 21 and 25.
3-4 cups/d
3-4 d/w
1601
60
1-2 cups/d
Be active in daily life.
(ex. 60 min/day of walking, etc., 1/week of athletic activities with sweating)
3-4 d/w
1-2 cups/d
Dont take very hot food or beverages.
Never
Ensure sufficient intake of fruit and vegetables.
1-2 d/w
18.07.0
1
Never
Keep the consumption of salt-preserved foods and added salt to a minimum.
keep salt intake at less than 8g/day for men and 7g/day for women and
consume foods with a salt content no more than once a week.
1-2 d/w
Eat a balanced diet.
3+ cups/d
Epidemiological study targeting Human
RCT
Cohort Study
Case-Control Study
Experimental Study
Animal Experiment, in vivo
In vitro experiment
Experience, opinion from authorities
1-2 cups/d
123g
3+ cups/d
Drink in moderation.
In any case no more than 23 g ethanol/day. Dont force yourself to drink if you
do not usually or cannot drink.
1-2 cups/d
Never
<1 cup/d
Do not smoke cigarettes.
Avoid passive smoking.
Never
Cancer prevention guideline for Japanese -Currently Recommended
Precautions for Cancer Prevention Applicable to Japanese
1
Priority Ranking of Evidence
<1 cup/d
Current Evidence-based Cancer Prevention
Recommendations for Japanese
(Lee KJ, Int J Cancer 2007; Inoue M, J Natl Cancer Inst, 2005; Luo J, Eur J Cancer Prev 2007; Kurahashi N, Cancer Sci 2009; Shimazu T, Int J Cancer 2009)
BMI and cancer risk
- meta-analysis of prospective observational studies Summary risk estimates by cancer sites in women
141 articles (1966-2007)
282137 incident cases
Systematic reviews
and meta-analysis:
Green-yellow
vegetables and
stomach cancer;
cohort and casecontrol studies
Renehan AG, et al. Lancet 2008;371:569-78.
BMI and Risk
of Death
(Non-smokers)
3.0
2.5
2.0
1.5
Asian Population (Asia Cohort Consortium) 1.1 million
2.43*
2.15* 1.72*
1.54*
Japanese men
1.51* 1.56*
1.23*
1.24*
1.0
BMI27.5
East Asia12%
South Asia8%
BMI20
East Asia20%
South Asia42%
1.02
1.00
1.00
1.07
1.00
0.97
0.5
1.11*
1.27*
1.01
0.94
East Asia
0.86
South Asia
0.0
Zheng W et al. New Engl J Med 2011;364:719-29
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Western population 1.46million
1.37
1.47
BMI27.5
Men34%
Women29%
BMI20
Men1.4%
Women
1.01
1.00
1.00
1.06
1.14
1.00
1.00
1.09
Western men
1.34
1.21
1.19
Men
1.44
2.93
2.06
2.51
1.88
The association
between alcohol
drinking and
colorectal cancer or
colon cancer appears
to be stronger in
Japanese populations
than in Western
populations.
1.44
Women
Berrington de Gonzalez A et al. New Engl J Med 2010;363:2211-9
Mizoue T, et al. Am J Epidemiol; 2008;167:1397-1406.
Cohort Consortium
Aim
POOLED ANALYSIS & COHORT
CONSORTIA
Efficient and effective utilization of existing cohorts
More precise/valid estimates with larger statistical
power.
Common exposures and common outcomes
Size
Country specific (Japan, US etc.)
Region (Europe, Asia, Nordic etc.)
Global (World BMI Consortium)
http://epi.ncc.go.jp/en/can_prev/index.html
Japan Cohort Consortium
The Asia Cohort Consortium
Since 2004
by Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan (since 2003)
[Mission]
Quantify risk of modifiable factors on cancer in Japanese.
Aimandscope
Final goal: Suggest methods involving lifestyle modification where definite effects can
be expected for decreasing the incidence of cancer in Japanese.
Cohort
JPHC Study Cohort I
Age
40-59
Baseline
1990
JPHC Study Cohort II
40-69
1993- 1994
78,825
JACC Study
40-79
1988-1990
110,585
MIYAGI Cohort
40-64
1990
47,605
OHSAKI health insuarance Cohort
40-79
1994
54,996
3-pref cohort MIYAGI
40-98
1984
31,345
3-pref cohort AICHI
40-103
1985
33,529
3-pref cohort OHSAKA
40-97
1983-85
35,755
TAKAYAMA Study
35-
1992
31, 552
Lifespan Study LSS
(Atomic bon survivors in Hiroshima/Nagasaki)
34-102
46-104
1978
1991
33,792
Total
Population size
61,595
Executivecommittee
Chairs:Daehee Kang(Korea),JohnPotter(US/NZ),
PaoloBoffetta (US),WeiZheng(US/China),Keun YoungYoo (Korea),Manami
Inoue(Japan),HabibAhsan(US/Bangladesh),Kee SengChia(Singapore)
TheACCCoordinatingCenter(Tokyosince2014)
n520,000
Serveasaplatform forcrosscohortcollaborativeprojectsandcombined
analysis.
Actasanincubatorfornewcohorts.
CohostedbyTheUniv.Tokyo(CoordinatingCenter)&NCC(DataCenter)
Manami Inoue(UT/NCC)PI,Eiko Saito(UT,NCC)Projectcoordinator
29 Participating Cohorts
A consortium of 29 cohort studies in 10 countries in
Asia. (1.7 million)
More than 150 researchers across Asia and the world
Cohort
Linxian General Population Trial
CHEFS Study
Shanghai Cohort Study
Shanghai Mens Health Study
Shanghai Womens Health Study
HEALS
Mumbai Cohort Study
Korean National Cancer Center Cohort
Korean Multi-Center Cancer Cohort Study
The Health Examinees Study
Seoul Male Cancer Cohort
Miyagi Cohort
3 Prefecture Miyagi
Ohsaki National Health Insurance Cohort
Ibaraki Prefectural Health Study
JPHC Study I, II
JACC Study
3 Prefecture Aichi
Takayama Study
Life Span Study Cohort
Taiwan Biobank
Community-based Cancer Screening Project
CVD Risk Factor two-Township Study
Malaysian Cohort Study
CLUSTer Cohort
Singapore Chinese Health Study
Singapore Consortium of Cohort Studies
Golestan Cohort Study
Total
Subjects
29,584
154,791
18,244
61,501
74,942
11,746
148,173
41,105
16,013
175,000
14,272
47,605
31,345
52,029
91,847
140,420
109,778
33,529
31,552
86,611
15,000
23,820
5,160
106,527
16,580
63,257
22,000
50,045
1,670,000
Cancer Epidemiology Consortia
Meeting
Year
Place
2004
Seoul, Korea
2005
Seattle, US
2005
Seoul, Korea
2006
2006
Singapore, Singapore
2007
LA, US
2007
Kuala Lumpur, Malaysia
2008
San Diego, US
2008
Beijing, China
10
2009
Denver, US
Washington DC, US
11
2009
NCC, Tokyo, Japan
12
2010
Washington DC
13
2010
Seoul, Korea
14
2011
Orando, US
15
2011
Dhaka, Bangradesh
16
2012
Taipei, Taiwan
17
2013
NCI, Bethesda, US
18
2013
UT, Tokyo, Japan
19
2014
Shanghai, China
Activity
Meeting: Annual (2016 Singapore)
Working group by research topic
Data analysis by remote access
(without transferring data from data center)
20
2015
UT, Tokyo, Japan
21
2016
Singapore, Singapore
22
2017
Tokyo (Omiya), Japan (IEA satellite)
Key Publication
1. Am J Epidemiol (2015) prostate cancer mortality
2. PLoS Medicine (2014) Total and cause-specific mortality
3. BMJ (2013) cardiovascular disease.
4. Am J Clin Nutr (2013) Meat intake
5. Eur J Cancer Prev (2013) pancreas cancer
6. Ann Oncol (2012) cancer of the small intestine
7. PLoS One (2011) diabetes.
8. N Engl J Med (2011) Body mass index and risk of death
Via Secured Network
Remote Access
Remote Access
Remote Access
Data Center (NCC, Tokyo)
Cancer Epidemiology Consortia
NCI Division of Cancer Control & Population Sciences
Epidemiology and Genomics Research Program
(NCI EGRP-supported)
NCI Division of Cancer Control & Population Sciences
Epidemiology and Genomics Research Program
(NCI EGRP-supported)
NCI
Consortia Alphabetized
AfricanAmerican Breast Cancer Consortium
Genetics and Epi of CRC Consortium (GECCO)
2008
Latin American Cancer Epi Conso (LACE)
Consortia by Cancer Category (# studies (#Genome consort))
2008
2008
AfricanCaribbean Cancer Consortium (AC3)
2006
Modifiers of BRCA1/2 (CIMBA)
2005
LEGACY: Breast Cancer Family Registry
2011
Bladder Cancer
African coloRectal cancer GrOup (ARGO)
2013
Epi of Endometrial Cancer Consortium (E2C2)
2006
LiFraumeni Exploration Conso (LiFE)
2010
Asia Cohort Consortium
2004
Germline Mutant Alleles Conso (ENIGMA)
2009
Lynch Synd Screen Network (LSSN)
2011
Asian Barrett's Consortium
2008
Genes, Environment and Melanoma (GEM)
1999
Melanoma Genetics Conso (GenoMEL)
1997
Asian Breast Cancer Consortium (ABCC)
2008
Genetic (GAMEON) Initiative
2010
African Prostate Cancer (MADCaP)
2007
2008
Genetic Epidemiology of Lung Cancer (GELCC)
1999
Ovarian Cancer Association Conso (OCAC)
2005
Brain Cancer
Liver
3(1)
Lung Cancer
1
2(1)
Breast Cancer
12(5)
Lymphoma
Asian Colorectal Cancer Consortium (ACCC)
Brain Tumor Epidemiology Consortium (BTEC)
2003
GLIOGENE
2007
Ovarian Cancer Cohort Consortium (OC3)
2009
Childhood Cancers
Ovarian Cancer
6(3)
Breast and Prostate Cancer (BPC3)
2003
HCC Epidemiology Consortium (HCCEC)
2013
Ovarian Cancer African Ancest (OCWAA)
2013
Breast Cancer (BCERP) Puberty Study
IMPACT
5(2)
Pancreatic Cancer
3(1)
2005
Pacific Ovarian Cancer Res Conso (POCRC)
Colorectal Cancer
2003
1999
Breast (BCAC)
2005
Int Barrett's and EAC Consortium (BEACON)
2005
Pancreatic Cancer CaseControl (PANC4)
2008
Breast (BC2OS)
2007
Int Childhood Cancer Cohort Consortium (I4C)
2005
Pancreatic Cancer Cohort Consortium
2006
Breast Cancer Family Registry (BCFR)
1995
Inherited Renal Malignancies (IConFIRM)
2013
Pancreatic Ca Genetic Epi (PACGENE)
2002
Cancer Genetics Network (CGN)
1998
Int Consortium of Bladder Cancer (ICBC)
2005
Pediatric Brain Tumor Consortium (PBTC)
1999
Clin Cancer Genetics (CCGCRN)
2014
Int Cons on Prostate Cancer Genetics (ICPCG)
1996
BRCA1/2 (PROSEModifiers Studies)
Childhood Leukemia Int. Consortium (CLIC)
2006
Int Head and Neck Cancer Epi Cons (INHANCE)
2004
Prostate Cancer Genome (PRACTICAL)
2007
CLL Research Consortium (CRC)
2006
International Lung Cancer Consortium (ILCCO)
2004
Prostate Cancer Transatlantic (CaPTC)
2005
NCI Cohort Consortium
2000
Int Lymphoma Epi Consortium (InterLymph)
2001
Radiogenomics Consortium (RGC)
2009
Colon Cancer Family Registry (CCFR)
1997
Int Multiple Myeloma Consortium (IMMC)
2007
Testicular Cancer Consortium (TECAC)
2012
Oncologic Emergencies Res Netwk (CONCERN)
2015
Keratinocyte Carcinoma Consortium (KeraCon)
2014
Women, Radiation Exposure (WECARE)
2002
Contralateral Breast Cancer (CCBC)
2011
Endometrial Cancer
Aesophageal Cancer
Prostate Cancer
Skin Cancers
Head and Neck Cancer
Testicular Cancer
Kidney Cancer
1(1)
Leukaemia
Multiple Cancers
6(3)
3(2)
1(1)
10(4)
http://epi.grants.cancer.gov/Consortia/
NCI
http://epi.grants.cancer.gov/Consortia/
IARC Monograph on the evaluation
of Carcinogenic Risks to Humans
Type of information used to identify carcinogens
IARC
IARC MONOGRAPH ON THE EVALUATION
OF CARCINOGENIC RISKS TO HUMANS
Epidemiological studies on cancer
in humans
(Scientific evidence of carcinogenicity
in humans)
Experimental studies on cancer
in laboratory animals
(Scientific evidence of carcinogenicity
in animals)
Studies of how cancer develops in
response to the agent
(Scientific evidence on cancer
mechanisms)
http://monographs.iarc.fr/
http://monographs.iarc.fr/
IARC Monograph on the evaluation
of Carcinogenic Risks to Humans
Cancer in
humans
Cancer in
experimental animals
Sufficient evidence
Limited evidence
Inadequate evidence
ESLC
Sufficient evidence
Limited evidence
Inadequate evidence
ESLC
*ESLC: Evidence suggesting lack of carcinogenicity
Voting
IARC Monograph on the evaluation of Carcinogenic Risks to Humans
Mechanistic and other
relevant data
Identify established and
other likely mechanistic
events to qualify the
mechanistic data
Strong
Moderate
Weak
Evidence in experimental animals
Sufficient
Evidence Sufficient
in
humans Limited
Inadequate
Overall Evaluation
Group 1
Carcinogenic to humans
Group 2A
Probably carcinogenic to humans
Limited
Inadequate
Group 2A
(probably
carcinogenic)
Group 2B (possibly carcinogenic)
Group 3 (not classifiable)
Group 2B
(possibly
carcinogenic)
ESLC
Group 2B
Possibly carcinogenic to humans
Group 3
Unclassifiable as to carcinogenicity in humans
Group 4
Probably not carcinogenic to humans
http://monographs.iarc.fr/
ESLC
Group 1 (carcinogenic to humans)
Group 1
Group 4
Overall Evaluation
Group 1
Carcinogenic to humans
Group 2A
Probably carcinogenic to humans
Group 2B
Possibly carcinogenic to humans
Group 3
Unclassifiable as to carcinogenicity in humans
Group 4
Probably not carcinogenic to humans
IARC Monograph on the evaluation of Carcinogenic Risks to Humans
IARC Monographs evaluate drinking coffee, mat, and very
hot beverages
Last evaluation (1991) Monograph vol. 51
Coffee was classified as possibly carcinogenic to humans
based on limited evidence of an association with cancer of
the urinary bladder from case-control studies and
inadequate evidence of carcinogenicity in experimental
animals.
Re-evaluation (2016) Monograph vol. 116
Overall coffee drinking was evaluated as unclassifiable as to
its carcinogenicity to humans (Group 3).
Lyon, France, 15 June 2016 An international Working Group of 23 scientists convened by the International Agency
for Research on Cancer (IARC), the cancer agency of the World Health Organization (WHO), has evaluated the
carcinogenicity of drinking coffee, mat, and very hot beverages.
A summary of the final evaluations is published today in The Lancet Oncology, and the detailed assessments will be
published as Volume 116 of the IARC Monographs.
The Working Group found no conclusive evidence for a carcinogenic
effect of drinking coffee. However, the experts did find that drinking very
hot beverages probably causes cancer of the oesophagus in humans. No
conclusive evidence was found for drinking mat at temperatures that are
not very hot.
www.thelancet.com/oncologyPublishedonlineJune15,2016http://dx.doi.org/10.1016/S14702045(16)30239X
IARC Monograph on the evaluation of Carcinogenic Risks to Humans
IARC Monograph on the evaluation of Carcinogenic Risks to Humans
IARC Monographs evaluate drinking coffee, mat, and very hot beverages
IARC Monographs evaluate drinking coffee, mat, and very hot
beverages (Vol. 116)
Very hot beverages
Drinking very hot beverages* was classified as probably carcinogenic to
humans (Group 2A).
*at about 70 C
Mat
Drinking mat at temperatures that are not very hot was not classifiable
as to its carcinogenicity to humans (Group 3).
(monograph 51Group2A)
Coffee
Drinking coffee was not classifiable as to its carcinogenicity to humans
(Group 3).
The large body of evidence currently available led to the re-evaluation of the carcinogenicity of coffee
drinking, previously classified as possibly carcinogenic to humans (Group 2B) by IARC in 1991.
After thoroughly reviewing more than 1000 studies in humans and animals, the Working Group found that
there was inadequate evidence for the carcinogenicity of coffee drinking overall.
Many epidemiological studies showed that coffee drinking had no carcinogenic
effects for cancers of the pancreas, female breast, and prostate, and reduced
risks were seen for cancers of the liver and uterine endometrium.
For more than 20 other cancers, the evidence was inconclusive.
Coffee
Drinking coffee was not classifiable as to its carcinogenicity to humans
(Group 3).
(monograph 51Group2B)
www.thelancet.com/oncologyPublishedonlineJune15,2016http://dx.doi.org/10.1016/S14702045(16)30239X
www.thelancet.com/oncologyPublishedonlineJune15,2016http://dx.doi.org/10.1016/S14702045(16)30239X
IARC Monograph on the evaluation of Carcinogenic Risks to Humans
IARC Monographs evaluate drinking coffee, mat, and very hot beverages
In assessing the accumulated epidemiological evidence, the current Working
Group gave the greatest weight to
well-conducted prospective cohort and population-based case-control studies
that controlled adequately for important potential confounders, including tobacco and
alcohol consumption.
Bladder cancer
There was not consistent evidence of an association with drinking coffee, or of an
exposure-response gradient from 10 cohort studies and several population-based casecontrol studies in Europe, the USA, and Japan.
10
In several studies, relative risks were increased in men, but were null or decreased in
women, consistent with residual confounding from smoking or occupational exposures
among men.
residual confounding
www.thelancet.com/oncologyPublishedonlineJune15,2016http://dx.doi.org/10.1016/S14702045(16)30239X
ATTRIBUTABLE CAUSE OF CANCER
IARC Monograph on the evaluation of Carcinogenic Risks to Humans
IARC Monographs evaluate drinking coffee, mat, and very hot beverages
Example of study with poor quality (Hospital-based case-control study)
Pancreatic
cancer
MacMahon et al. (1981)
367 cases (216 male, 151 female) under 80 years of age identified in 11
hospitals in Boston and RI.
643 hospital controls
(Diseases other than G-I, 254; cancers other than G-I, 157; G-I diseases other
than cancer, 117; G-I tract cancers, 115)
Multivariate OR (adjusted for age, sex, and smoking)
Non-drinkers OR=1.0 (Ref)
1-2 cups/day: OR=1.8 (95%CI, 1.0-3.0)
3+ cups/day: OR=2.7 (95%CI, 1.6-4.7) (P-trend= 0.001)
Prestige Bias
Famous epidemiologists authored, published in prestigious journal (NEJM)
prevented from denying the association between coffee and pancreatic cancer
for long period.
NEJM
MacMahon B, Yen S, Trichopoulos A, Warren K, Nardi G (1981a). Coffee and cancer of the pancreas (Letter to the Editor). N Engl J Med.
304(11):6056.
MacMahon B, Yen S, Trichopoulos D, Warren K, Nardi G (1981b). Coffee and cancer of the pancreas. N Engl J Med. 304(11):6303.
ATTRIBUTABLE CAUSE OF CANCER
The Cause of Cancer in the US
Burden?
Factors
Avoidability of cancer deaths
RISK FACTORS
all contribute to
RR: large or small
Prevalence: large or small
Association with cancers
Rare or common?
Number of incidences / deaths large?
Many cancers or one specific cancers?
CANCER STATISTICS
Burden
Association
0.0001%
Rare cancer
One cancer
Small
50%
Common cancer
Many cancers
Large
70%
Common cancer
One cancer
Middle
Alcohol, 3
Reproductive
Perinatal factors, 3
factors/growth, 5
Total cancer
??
%
20
Passive smoking
Passive smoking
1.9
1.5
0.8
0.5
Fruit intake
0.7
0.7
Vegetables intake
0.7
0.7
Physical inactivity
0.3
0.2
20
Alcohol drinking
Incidence
Mortality
40
5.0
6.2
1.2
1.6
17.5
19.4
Infection
22.8
23.2
9
8.6
Alcohol drinking
body mass index
Tobacco smoking
0.2
0.4
%
0
2.5
2.5
60
Tobacco
53.3
56.9
Diet
35
Food additives
<1
Reproductive and sexual behavior
Occupation
Pollution
Industrial products
<1
Medicines and medical procedures
Geophysical factors
Infection
10?
unknown
61
Japan
2005
Korea
2009
France
2000
3.9
29.7
5.0
20.9
2.3
27.0
6.1
23.0
15.6
15.8
10.1
2.4
5.9
0.3
9.0
2.5
3.0
0.5
10.8
4.5
4.6
3.3
3.0
Overweight/obesity
0.08
1.5
0.8
1.6
1.5
2.2
1.4
3.3
4.1
6.9
2.5
4.5
Insufficient PA
0.5
0.3
0.3
0.6
0.1
1.4
0.5
4.2
0.4
1.7
0.5
2.9
Infections
3.7
28.8
21.8
22.8
17.5
24.5
15.4
2.6
4.4
2.5
3.7
2.4
Repro
1.0
1.3
1.9
Exogenous hormones
0.06
0.4
0.8
2.2
1.1
2.4
1.7
Salt intake
1.2
1.2
0.7
1.6
1.1
Insufficient fruit
13.3
9.2
0.7
0.8
Fruit intake
0.8
0.8
Insufficient vegetable
4.0
2.6
0.7
0.4
Vegetables intake
0.4
0.4
Salt
1.9
1.2
Physical inactivity
0.6
0.4
Insufficient fiber
Red/processed meat
Exogenous hormone use
0.4
0.2
Pollution
2.8
1.6
Radiation
UV
Insufficient breastfeeding
All above
(Inoue M et al. Ann Oncol. 2012 May;23(5):1362-9)
Australia
2010
30.0
body mass index
27.8
29.9
UK
2010
Alcohol
Occupation
All above
Adult diet/obesity,
30
Sedentary
lifestyle], 5
China
2005
Women
60
29.7
34.4
Infection
Salt intake
40
PAF % (Incidence)
Attributable cause of cancer in Japan, 2005
Incidence and mortality
Men
30
Alcohol
Harvard Center for Cancer Prevention:
Harvard Report on Cancer Prevention,
Volume 1: Causes of Human Cancer,
Cancer Causes Control 1996 ;7:S3-S59.
Family history of
cancer, 5
Occupational
factors, 5
Tobacco
Tobacco, 30
virus/other
biologic agents, 5
60
Prescription
drug/medical
pullution, 2
procedures, 1
Ionizing/ultraviole
Salt/other food
t radiation, 2
additives/contami
nants, 1
Socioeconomic
status, 3
.. Burden
1.5
Tobacco smoking
30
Doll R, Peto R. The causes of cancer: quantitative
estimates of avoidable risks of cancer in the United States
today. J Natl Cancer Inst. 1981;66(6):1191-308.
35
By tobacco smoking (without tabacco smoke)
Absolute
Prevalence
All risk factors
By diet (improving diet)
Harvard Report1996) Environmental
Relative
RR
% of all
cancer
deaths
Doll & Peto (1981)
ALL OF THE ABOVE
0.5
1.5
1.2
0.3
0.2
6.1
3.4
0.9
0.2
1.4
1.7
2.3
2.1
3.5
1.9
2.7
1.6
0.1
0.2
2.5
0.3
4.9
2.4
1.7
2.0
1.5
2.8
53.3
27.8
45.7
25.6
3.5
3.6
7.1
5.0
45.3
40.1
32.8
30.6
Attributable cause of cancer comparison by country
The number of deaths attributable to risk factors in Japan, 2007
China
Japan
Korea
France
UK
Australia
China
Japan
Korea
France
UK
Australia
10
China
Japan
Korea
France
UK
Australia
20
China
Japan
Korea
France
UK
Australia
30
China
Japan
Korea
France
UK
Australia
Men
0
Smoking
Alcohol
Obesity
Physical inactivity
infection
LDL
Women
BMI
Alcohol
Obesity
Physical inactivity
T1
0
Smoking
France
UK
Australia
China
Japan
Korea
France
UK
Australia
China
Japan
Korea
France
UK
Australia
10
China
Japan
Korea
France
UK
Australia
20
China
Japan
Korea
France
UK
Australia
30
China
Japan
Korea
infection
20
40
60
80
100
Ikeda N, et al, Lancet 2011;378(9796):1094-105.
Purpose of cancer screening
CANCER SCREENING
120
Death(x1000)
200520052009200020102010
Reduction in the cancer mortality rate as a result
of early detection.
Not just detecting as many cancers as possible.
Organized screening and opportunistic screening
Screening
method
Organized screening:
Organized screening and opportunistic screening
Organized Screening
Reduce the overall mortality rate of the
subject group
Reduce the individuals risk of death
Preventive measures carried out as a
public medical service
Medical service provided as an option
by medical institutions, screening
agencies, etc.
All members of a group
(residents of a specific age group, etc.)
Not defined
Screening fee
Public funds used
Individual covers the full cost
Benefits and
Harms
Maximization of benefits for the group by
The balance of benefits and harm is
giving consideration to a balance in
determined at an individual level
benefits and harm using limited resources
Purpose
Conducted for the purpose of reducing the mortality
rate of an entire group, and carried out as an public
preventive measures.
Select screening with established effectiveness.
Overview
Target
Opportunistic screening
Screenings other than organized screening.
Individual can choose.
Preventive benefits from insurer
Opportunistic Screening
Cancer screening rate (%) in Japan
Current organized cancer screening in Japan
Site
start
Method
Stomach
1982
Interview+Stomach X-ray/gastroscopy
50+
Biannual
Colorectum
1992
Interview+Fecal occult blood test
(Immunoassay)
40+
Annual
Interview,+Chest X-ray+sputum cytology
(smokers)
40+
Men 2010
100
Men 2013
Women 2010
Women 2013
90
80
70
60
Lung
Cervix
1987
1982
Annual
50
40
Interview+Inspection, Cytology/pelvic
examination
20+
Interview+Mammography
40+
Biannual
30
47.5
45.8
36.6
33.8
28.3
37.4
26.4
23
41.4
34.5
28.1
23.9
32.7
28.7
34.2
30.6
20
10
Breast
1987
Biannual
Stomach
Lung
Colorectum
Crevix
Breast
Comprehensive Survey of Living Conditions 2013, by Ministry of Health, Labour and Welfare, Japan
Cancer Screening rate (%)
Breast and Cervical cancer
Cancer
screenin
100
g rate
US
80
US
UK
UK
60
40
Japan
Japan
20
EPIDEMIOLOGICAL DATA FOR
EVALUATING HEALTH POLICY
Breast cancer screening
Cervical cancer screening
Japna: 19
US: CDC,BRFSS(Behavioral risk factor surveillance system 2008)
UK: NHS Cancer Screening ProgramAnnual report (2009)
Oh CM, et al. Cancer Res Treat. 2015 Jul;47(3):362-9.
Elevated incidence of Thyroid cancer in Korea
Korean National Cancer Registry Database
Thyroid cancer in Korea is the highest in the world.
Men
Incidence
Mortality
Cholangiocarcinoma among workers in the printing industry
A cluster of 11 cases of CC was observed in small Japanses printing firm. (2013)
Examined if this also happened in four Nordic countries (NOCCA data base)
(
Women
Incidence
Mortality
Nordic Occupational Cancer Study (Finland, Iceland, Norway, Sweden), Age 30-64 ys
Men
SIR
HCC
Intrahepatic CC
Cohort by linking
Occupation information from census
National cancer registry data
Extrahepatic CC
5
3.54
4
3
Theincreasedincidenceofthyroid
cancerislargelyaresultofthe
periodeffect,stronglysuggestthe
roleofthyroidscreening.
Association between number
of ultra-sonographs and
thyroid cancer incidence in
Korea 2000-2011.
2.34
1.35
2.01
1.13 1.18
2.38
2.22
1.09
3.91
2.15
1.37 1.41
1.19
1.17
1.37
Men
Printers and related workers: 74949
Followed over 45 year period
HCC: 142
Intrahepatic CC: 21
Extrahepatic CC: 43
1.48
1
0
All
Typographers
Printers
Lithographers Bookbinders
Other
SIR of intrahepatic CC especially
elevated for Printers and
lithographers.
Vlaanderen J et al. Occup Environ Med 2013;70:828-830.
