This presentation is dedicated to my women friends

• Some who died of cancer such as Francesca Capeletto or 2 of the 4 nominees for France for the 1000 women for the Peace Nobel Prize 2005, Dr Solange Fernex and Christina Pezenas de Montcel

• Others who are bravely fighting against metastatic breast cancer, such as Dr Annie Hubert

Cancer and globalization:A European perspective with a focus

on women’s health

Annie J. Sasco, MD, DrPHTeam leader, Epidemiology for Cancer Prevention

Inserm, U 593Victor Segalen Bordeaux University, France

Visiting Professor, University of Sao Paulo, Brazil

This presentation solely reflects the point of view of the author and cannot be taken as official views of the Inserm, the University or any other institutions

XXI st century

• A century of globalization• For commercial products and life-

style• For disease occurrence (cancer,

reproductive outcomes, etc..)• For action

Cancer: Evolutionary perspective• Not just a disease of the old age in

western populations• An ancient phenomenom (dinosaurs,

mummies) which has always been part of (pluricellular) life

• Existing in all species (humans, animals)

• In all populations of the world (with different frequencies)

• Increasing over time

World cancer burden in 2002

10.9 million new cancer cases- 5.1 in women- 5.8 in men

6.7 million cancer deaths- 2.9 in women- 3.8 in men

ParkinParkin et al., 2005et al., 2005

Geography of cancer

after correction for different population sizes and age-structures

→age-standardized (world population) rates

enabling us to compare populations

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 man-years

Globocan 2000, 2001

*ASR : age-standardized (world) incidence rate, expressed as number of new cases per 100 000 woman-years

Breast cancer

1 cancer out of 10 in the world

Concerns almost exclusively women

Sasco, 2004Sasco, 2004

Incidence of breast cancer : ASR* (world) (all ages) Korea

18,612,7

20,920.0

0

20

40

60

80

100

Busan Daegu Kangwha Seoul

*ASR : age-standardized incidence rate expressed in number of new cases per 100 000 woman-years

Parkin et al, 2002

Incidence of breast cancer : ASR* (world) (all ages) Japan

36,6 33,1 29,823,6

28,328.0

0

20

40

60

80

100

Hiroshima Miyagi Nagasaki Osaka Saga Yamagata

*ASR : age-standardized incidence rate expressed in number of new cases per 100 000 woman-years

Parkin et al, 2002

Incidence of breast cancer : ASR* (world) (all ages) China

24,6

36,2

9,1

27,2 31,324,7

18,110.0

0

20

40

60

80

100

Beijing HongKong

Jiashan Qidongcountry

Shanghai Taiwan Tianjin Wuhan

*ASR : age-standardized incidence rate expressed in number of new cases per 100 000 woman-years

Parkin et al, 2002

How can we explain these differences ?

Life styleGenetics

Environment

How do we evaluate the relative importance of these influences ?

The study of migrant populations

Breast cancer incidence rate by age in various groups of population

from Waterhouse et al., 1982

Sasco, 1989

San Francisco, WhiteSan Francisco, ChineseLos Angeles, ChineseChinese, Shanghai (P.R.C.)

Temporal epidemiology

- age- time-trends

Breast cancer rates by age - Singapore

Rate (per 100,000)

0

50

100

150

200

0-14 15-44 45-54 55-64 65+

IncidenceMortality

Age (years)

Expressed in number of new cases or deaths per 100 000 woman-yearsGlobocan 2000, 2001

Trends in world cancer burden

3,2 3,9 4,3 5,3

3,13,8 3,8

4,7

0

2

4

6

8

10

12

1980 1985 1990 2000

womenmen

6.37.6 8.1

10.0

Million

Total number of annual estimated new casesTotal number of annual estimated new cases

based on the mostbased on the most 1616 1818 2525 2424

common cancerscommon cancers

Parkin Parkin et al, 1988et al, 1988 19931993 19991999 20012001

Time-trends in cancerWorld breast cancer burden

471063324100298000224200

579285

471500422000347900

0

300000

600000

900000

1200000

1980 1985 1990 2000

industrialized

other

572100720000

795600

Total number of annual estimated new Total number of annual estimated new casescases Sasco, 2003

adapted from Parkin et al 1988, 1993, 1999 and Parkin 2001

1050348

What are the global trends in cancer ?

• In terms of burden of disease : Clear increases for most cancers at most places due to :– population increases– aging of the population– true increases of the disease

• In terms of age-standardized rates :Contrasting pictures depending on :– mortality / incidence– geography

Mortality of breast cancer Mortality of breast cancer -- TimeTime--trendstrendsWorldWorld

19501950 19551955 19601960 19651965 19701970 19751975 19801980 19851985 19901990 19951995

JapanJapan

USAUSA

FranceFrance

NetherlandsNetherlands

ItalyItaly

SwedenSweden

UKUK

Incidence - Breast cancer - Women

0

20

40

60

80

100

1955 1965 1970 1975 1980 1985 1990 1995

USA, ConnecticutUSA, Connecticut

Japan, MiyagiJapan, Miyagi

UK, BirminghamUK, Birmingham

France, BasFrance, Bas--RhinRhin

Canada, AlbertaCanada, Alberta

DenmarkDenmark

Sasco, 2004

Age-standardized (world population) incidence rates, expressed in number of new cases per 100,000 woman-years

based on Cancer Incidence in Five Continents, volumes I (1966) to VIII (2002)

Incidence of breast cancer –Time-trends - Asia

0

10

20

30

40

50

1955 1965 1970 1975 1980 1985 1990 1995

Japan, MyagiJapan, Myagi

India, BombayIndia, Bombay--MumbaiMumbai

HongHong--KongKong

China, ShanghaiChina, Shanghai

Sasco , 2004

based on Cancer Incidence in Five Continents, volumes I (1966) to VIII (2002)

Age-standardized (world population) incidence rates, expressed in number of new cases per 100,000 woman-years

What are the global trends in cancer ?• In terms of incidence rates :

– some almost universal decreases (stomach cancer)

– some decreases for some cancers in countries previously having high rates

ex : - male lung cancer and some other tobacco/alcohol related cancers in Northern America and Europe

- some other cancers (plateau for breast cancer in the USA or Canada)

– increases for most cancers in many countries- increases in the less developped countries (Africa, China,

India, ...)- increases still occuring in parts of the Western world

(Central European countries) and for specific cancer types (tobacco-related cancers but also hormono-dependant cancers)

Controversy surrounding increases in cancer rates

• How much is due to ?– improvement in therapy and impact on mortality

• clear role for testicular cancer in young men• role in survival from childhood cancer

– earlier diagnosis• true for most cancers with some impact on mortality• unlikely to affect incidence rates to any notable extent

– screening• undeniable role for prostate cancer in the USA• some role for breast cancer

– real increases• My own contention is that most of the

increases are real

Etiologic epidemiology: the search for the causes of cancer

• Genetics less than 10% of all cancersa role for genetic polymorphisms and epigeneticphenomena

• Life-stylesmoking, alcohol drinking, diet, physical exercise, sunexposure, sexual and reproductive life, use of legal andillegal drugs

• Environment

Other identified causes of cancer

• Many recognized carcinogenschemicalphysical agentsbiological

• Present in occupational and environmental settings

The IARC Monographs programme on the evaluation of carcinogenic risks to humans

Classification

Group Number1 : Carcinogenic to humans 1082A : Probably carcinogenic to humans 642B : Possibly carcinogenic to humans 2403 : Not classifiable as to carcinogenicity

to humans 4874 : Probably not carcinogenic to humans 1

Total evaluated 900

How much of cancer is due to the presence of carcinogens in

the environment?The answer will depend on:

• the cancer considered• the definition of the environment• the person answering the question

from 2 to 80%

A very difficult question

• Difficulty in identifying precise compoundsof interest (and their metabolites)

• Difficulty in assessing low dose effects

• Difficulty in estimating cumulativeexposures

• Huge difficulty in assessing potential interactions between many low dose agents

Three approaches to primary cancer Three approaches to primary cancer preventionprevention

Genetic interventionGenetic intervention

Modulation ofModulation ofcarcinogenic carcinogenic mechanismsmechanisms

GeneGene

EnvironmentEnvironmentCancerCancer

Avoidance of risk factorsAvoidance of risk factors

Sasco, 1995Sasco, 1995

Avoidance of risk factors

• Recognition of risk factors

• Levels of control

individualcollective

European Code Against Cancer (third version)Many aspects of general health can be improved, and many cancer deaths prevented, if we adopt healthier lifestyles:

1. Do not smoke: if you smoke, stop doing so. If you fail to stop, do not smoke in the presence of non-smokers.

2. Avoid obesity.3. Undertake some brisk, physical activity every day.4. Increase your daily intake and variety of vegetables and fruits: eat at

least five servings daily. Limit your intake of foods containing fats from animal sources.

5. If you drink alcohol, whether beer, wine or spirits, moderate your consumption to two drinks per day if you are a man or one drink per day if you are a woman.

6. Care must be taken to avoid excessive sun exposure. It is specifically important to protect children and adolescents. For individuals who have a tendency to burn in the sun active protective measures must be taken throughout life.

Boyle et al, 2003Boyle et al, 2003

What about exposures which are beyond the level of control of the individual?

examples : - Air pollution and cancer- Use of growth promoters in animal production- Pesticide residues in food- Exposure to radiations

The precautionary principle should, whenever possible, be enacted to prevent unnecessary exposures in particular at specific periods of vulnerability (fœtal life,childhood, ...) with a triple objective:

- protect all- protect the most susceptible- social justice

European Code Against Cancer (third version)

7. Apply strictly regulations aimed at preventing any exposure to known cancer-causing substances. Follow all health and safety instructions on substances which may cause cancer. Follow advice of National Radiation Protection Offices.

Boyle et al, 2003

But :- What about carcinogens which are not regulated?- Which rules should apply to low dose exposures?- Is there room for the precautionary principle?

How much did we need to act ?John Snow and the cholera epidemic in London

Knowledge:- maps of cases in London- map of water supply

Action:- Snow removed the handle of the pump

in absence of absolute proofin the name of precautionary principle

How much do we now need to act?

• evidence of carcinogenicity• evidence of toxicity• balance of benefits/harms to the person

exposed

For exposures which can be controlledby the individual, correct information ofthe person exposed (labelling) and freedomto decide ?

The European REACH directive

Register, Evaluate and Authorize ChemicalsA screening effort to try to prove inocuity of products

before putting them on the market rather than later demonstrating their dangerProblematic choice of which products to evaluate (quantity)Far from being sufficient but a step in the right direction

The need to reform the international trade

• The role of the World Trade Organisation in health related mattersMy own experience: the use of growth promoters inanimal productionCountries cannot defend the health of their populationsResisting the entry to dangerous products is not an unfairbarrier to free tradeRegulations should be uniform all over the world

Not a conclusion: The way to the future!• Women have long demonstrated they are

survivors, much more resistant than men, and yet never getting their fair share

• Women care about the future because many of them had a future, independant being growing inside of them when they were pregnant and they know the responsability of bringing a child to the world

• They are the only ones capable of changing the world, making it a better, cleaner, fairer place to live

• We owe to our daughters to start NOW!