Translation of the document
“Enquête Agrican – Agriculture & Cancer”
November 2014
Cover page .................................................................................................................................. 3
Page 0 (Foreword) ....................................................................................................................... 3
Page 1 (content) ......................................................................................................................... 4
Page 2 – (photos) ......................................................................................................................... 4
Page 3 - Preamble - The agricultural world with regard to cancer ........................................ 4
Page 4 – Cancer: First mortality cause in France before cardiovascular diseases .............. 5
A difference between incidence and mortality ......................................................................5
Page 5 – What is a cancer register?........................................................................................... 6
What is a cancer register? ............................................................................................................7
There are two coexisting types of cancer registers..................................................................7
Data collated by the registers .....................................................................................................7
The objective of the data collection ..........................................................................................7
Departments participating in the study .....................................................................................8
Page 6 – The job: risk factor for cancer? ................................................................................... 8
What is an occupational disease? .............................................................................................8
Who can ask for acknowledgement of an occupational disease? ....................................8
Page 7 – Cerfa document ........................................................................................................... 9
Page 8 – Recognition of a professional disease ....................................................................... 9
Assumption of occupational origin .............................................................................................9
Complementary system ................................................................................................................9
Page 9 - Services that people with a recognised occupational disease are entitled to ... 10
Page 10 – Limits of the studies conducted until now in agricultural environment .............. 10
Limits linked to the lack of knowledge on the development of cancer ............................11
Limits of studies conducted in agricultural environment ......................................................11
Page 11 – Routes of progress in the knowledge on the link between agriculture and
cancer......................................................................................................................................... 11
In France: the Agrican cohort....................................................................................................11
In the US: agricultural health study ............................................................................................12
Page 13 – The Agrican Cohort. The farming world and its risk factors.................................. 12
Page 14 – The AGRICAN cohort – reminders.............................................................................. 12
Thank you for your participation................................................................................................13
The stages of the cohort .............................................................................................................13
Page 15 – Characteristics of the participants ......................................................................... 14
Characteristics of the participants ............................................................................................14
Page 16 – Health of cohort participants compared to the health of the general French
population .................................................................................................................................. 15
Are the death causes similar to the ones of the general public? .......................................15
Mortality by “important” causes................................................................................................15
Page 17 – Mortality by cancer ................................................................................................. 16
Limits of the comparison of death causes ...............................................................................17
Page 18 – Is the agricultural population more often affected by certain cancers than the
general population? .................................................................................................................. 18
Page 19 – are these results confirmed by other studies? ......................................................19
Page 20 – skin cancer is more frequent in the farming environment ................................... 20
Monitoring and screening ..........................................................................................................22
Page 22 – Respiratory diseases, cancerous or not ................................................................. 23
Identification of risk factors in the cohort ................................................................................ 23
Page 23 – Agricultural activities linked to broncho-pulmonary cancers ............................ 23
Which exposures could decrease the risk of broncho-pulmonary cancers? ...................24
Page 24 – Which agricultural exposures could increase the risk of developing bronchopulmonary cancer? ................................................................................................................... 25
Page 25 – Which agricultural exposures could increase the risk of developing chronic
bronchitis? .................................................................................................................................. 26
Agricultural activities linked to the risk of developing asthma .............................................26
Page 26 – perspectives 2015-2016 ........................................................................................... 27
The pesticides................................................................................................................................27
Page 27 – financing of projects in agricultural environment, conducted by the cancer &
preventions team ....................................................................................................................... 28
The other studies ...........................................................................................................................28
The financials in our projects ......................................................................................................28
Page 28 - Glossary ..................................................................................................................... 29
Page 29 – Organisation and functioning of the AGRICAN cohort ........................................... 30
The steering committee ..............................................................................................................30
The members of the scientific council ......................................................................................30
Your data will remain strictly confidential ................................................................................30
2
Cover page
Agrican Investigation
Agriculture & cancer
November 2014
Page 0 (Foreword)
Dear Member of the AGRICAN study,
Almost 10 years ago you accepted to participate the AGRICAN cohort study.
Therefore in the name of the entire research team we would like to thank you to have
answered our questions already once and we thank you for having accepted this
new questionnaire…
I hope that the information that we shared with you in July 2011 and the ones
presented in this second bulletin will be of interest to you and useful to your health.
The AGRICAN cohort is one of the most important one in the world to investigate health
in agriculture, and one of the only ones to consider active as well as retired farmers,
employees and operators, considers women and men, people from the cooperative
sector, agricultural services, wood industry, forestry, and many more … Also, the
information provided is unique and particularly important for public health.
One part of the bulletin (pages 16 -21) describes the health of cohort members in
comparison to the general French population and sheds light on particularities. The
other part (pages 22-25) presents the first analyses that we have conducted to
understand the factors influencing participants health.
We checked disease by disease to try to understand “professional working
environment” factors acting over time that could explain the exceedences observed
in the agricultural environment: history of crops and livestock, tasks carried out,
pesticides used, and other nuisances present in the agricultural environment… Also
we share with you the results obtained to date concerning lung cancer, asthma and
chronic bronchitis.
Year after year, the AGRICAN study provides more results, new knowledge on diseases
in the agricultural environment. This is why your long-time commitment is particularly
precious.
Thanks to you research can progress and provide routes for a better prevention of
risks to health in the agricultural environment.
Thank you in advance for the time that you dedicate to complete this new
questionnaire: it will provide us with complementary information that are very useful
to our research.
For the Agrican team:
Pierre Lebailly, coordinator of the AGRICAN study
3
Agrican team within the cancer & preventions unit
Stéphanie Perrier, database manager
Céline Meyer, secretary
Valérie Tribouillard, input operator
Séverine Tual, researcher
Catherine Gaultier, secretary
Clémentine Lemarchand, PhD student
Noémie Levêque-Morlais, database manager
Yannick Lecluse, technician-investigator
Anne-Sophie Lacauve, Research assistant
Elodie Niez, Research assistant
Romain Pons, PhD student
Pierre Lebailly, researcher, coordinator
Maryline Niez, input operator, webmaster
Bénédicte Clin-Godard,researcher
Mathilde Boulanger, PhD student
Page 1 (content)
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Cancers are the 1st cause of mortality in France on top of cardiovascular diseases
Your profession, risk factor for cancer?
The limits of the studies conducted until now in the agricultural environment
Tracks for progress with regard to knowledge of links between farming and cancers
The Agrican cohort – The farming world and risk factors
Reminders
Comparison of participants health of the cohort with the one of the French population
Skin cancers are the most frequent in the farming environment
Respiratory diseases: identification of risks within the cohort
Perspectives 2015-2013
Financing of projects in agricultural environment conducted by the cancer &
prevention team
Glossary
Page 2 – (photos)
Page 3 - Preamble - The agricultural world with regard to cancer
It is nowadays admitted that farm operators in industrialized countries have generally
a better life expectancy than the general population.
They have indeed a better health, in most cases they smoke less than the general
population.
4
The AGRICAN data reveal more frequent smoking amongst agricultural employees
than farm managers. However, the gap is getting smaller between younger farmers 1
and the general population (see AGRICAN information bulletin n°1).
Over time, the life expectancy of farmers could therefore get closer to the one of the
general population.
Studies conducted in other countries have shown that certain cancers are more
frequent in the farming community. These are blood cancers such as leukaemia,
lymphoma, … skin cancers, prostate cancer. It is not yet known which factors could
cause such an increased frequency.
Page 4 – Cancer: First mortality cause in France before cardiovascular diseases
A difference between incidence and mortality
The development of cancers over the last 30 years in France stands out by a
significant increase in the incidence 2 and a considerable decrease of the risk of
death.
The decrease of the mortality through cancer can be explained partly through the
more efficient treatments, but also through a decrease of the number of certain
cancers.
The incidence increase is partly linked to the improved means of screening, allowing
the identification of cancers at a very early stage.
There are thus more cases of cancer, but they are less lethal.
Graph entitled: Evolution of the incidence and mortality per cancer in France in
women and men between 1980 and 2011 (FRANCIM data). FRANCIM (FRANce
Cancer Incidence Mortality): association law 1901 grouping French cancer registers.
1 Women and men working on a farming business regardless of their status (leader, non-
employee, partner collaborator (rem . “ conjoint”), or permanent or temporary employees)
2 the incidence of a disease is the number of new patients during a given period
5
Table entitled: Period of creation of general registers and covered population
Page 5 – What is a cancer register?
Almost 150,000 persons die every year in France from cancer
Almost 355,000 new cancer cases in France
Almost 30% of deaths of the Agrican cohort are linked to cancers
6
What is a cancer register?
The registers are in charge to systematically register the content of an “event”, which
is most often a disease, in a specific geographical zone (a department, in most
cases). First French registers have been created since 1975. In 1986, the creation of
the National Committee of Registers (CNR) provided for the inclusion of the registers
into a national policy of public health and research.
There are two coexisting types of cancer registers
The general register registers all cancer cases on their territory, without being specific
on the type of cancer. To date, there are 17 general registers on the entire French
territory (metropolitian and overseas) that cover approximately 15 million people.
These represent about 23% of the French population.
The specialized registers only register certain specific cancer types. There are 10
specialized departmental or multi-departmental registers and 2 national registers for
cancer in children.
Data collated by the registers
For each new patient active data retrieval is conducted with the medical dossier. The
collected data concern the patient’s identity, age, gender, history of cancer and all
elements of the (cancer) diagnosis (symptoms, exact description of tumour etc.)
Graph title: Geographical distribution of the cancer registers
The objective of the data collection
The data collected in the registers allow for a very close monitoring of cancers, as
well as a quality research in terms of clinical epidemiological data on cancer causes.
The same applies to the AGRICAN study.
7
Departments participating in the study
When the AGRICAN study was set up, only the departments that had a register in 2005
have been selected. The objective was to study the incidence of cancers within the
cohort, without having to interview every person that participated in the study.
Page 6 – The job: risk factor for cancer?
The causes of cancer in the French population as well as in the farming community
are not all understood. Amongst the known causes explaining partly certain cancers,
one could cite certain habits such as smoking, food or alcohol, as well as genetic
predisposition, environmental and occupational exposure.
With the exception of certain cancers for which the role of certain environmental and
occupational exposures is well known (e.g. asbestos and mesothelioma, exposure to
pesticides containing Arsenic and bronchopulmonary cancer), the effect of
occupational exposure remains poorly understood and is often under-estimated.
However, France developed a system of social protection that allows for the
recognition of an occupational cause in the case of selected pathologies.
What is an occupational disease?
A disease is recognized as “occupational” if it responds to one of the 3 proposals,
which are listed in the social security code:
-1. A disease listed in the table of occupational diseases is contracted under the
conditions listed in this table
-2. A disease that does not fulfil one or several conditions listed in the abovementioned table, but which is recognised as “of occupational origin” by the Regional
Committee for Recognition of Professional Diseases (“Comité Régional de
Reconnaissance des Maladies Professionelles CRRMP”).
-3. A disease that caused death or a permanent inability of the victim to at least 25%
that does not fulfil one single condition of the above mentioned table, but which is
recognised as being of occupational origin (CRRMP).
Who can ask for acknowledgement of an occupational disease?
Every person suffering from a disease (employee or non-employee), or any entitled
person in case of death can request the acknowledgement with his/her physician.
This request will then be forwarded to the social security organism of the victim.
To be receivable, every “occupational disease” request must be submitted with the
Cerfa document “Declaration of occupational disease” (“Déclaration de maladie
professionelle”). This document can be downloaded from the MSA within 2 years
after the issuing of the first medical certificate hinting at a possible link between the
disease and occupational exposure.
This declaration must be accompanied by the initial medical certificate describing
the nature of the disease, in particular the symptoms listed in the table of professional
8
diseases and noted as well as the likely development and indicating a possible link
between the pathology and the professional activity of the victim.
Page 7 – Cerfa document
Depicts the second page of the CERFA document . downloadable here.
Page 8 – Recognition of a professional disease
When the dossier is accepted, the social security agency will forward the request
under the administrative and medical obligations and informs the employer and work
inspector. The social security agency decides to acknowledge (or not) the
occupational cause of the disease and notifies the victim (which can be an
employer) and the employer within an initial delay of 3 months. This timeframe can
be extended to 6 months in case of an investigation or a complementary medical
examination.
Assumption of occupational origin
Any disease is systematically presumed of occupational nature if it responds to either
the medical, professional and administrative conditions listed in the table of
occupational diseases of the rural code for workers (employees and managers), the
agricultural regime (67 tables) or the social security code for employees within the
general regime (112 tables). The victim must not bring the evidence that there is a
causal link between its work and its disease.
Example: A person has handled arsenic for more than 10 years during work and
declares having developed lung cancer (disease recognised in the table as n°10) in
less than 40 years after his/her last exposure to arsenic. This cancer will systematically
be recognised as of occupational because all conditions in the table are fulfilled.
Complementary system
When one or more conditions of the occupational disease table are not fulfilled, it is
the CRRMP, (consisting of medical experts) that will draw the direct causal link
between the professional disease and the work.
There are two categories of diseases:
1 – Diseases listed in a table of occupational diseases for which one or several
conditions (Management deadline, duration of exposure, restrictive list of tasks) are
not fulfilled
2 – Diseases not listed in a table of occupational diseases but which are caused by
the victim’s professional activity and which did cause its death or permanent partial
invalidity (“Incapacité Permanente Partielle - IPP) of at least 25%.
Extract of table n°10 of the agricultural scheme (arsenic)
Designation of the disease:
Primary bronchial cancer
Management deadline:
exposure
40 years, provided that there were 10 years of
Indicative list of basic tasks that may cause the disease
9
- Any handling or use of arsenic or its mineral components, in particular in vineyard
treatment (anticryptogamic treatment)
- Handling of wood treated with products based on arsenic of its components
To date there are very little occupational disease tables that link cancer to an
agricultural exposure. This situation can partly be explained by the fact that it is
impossible to conclude with certainty on the effects of certain occupational
exposures. The lack of data on certain cancers or certain exposures is another
element.
Page 9 - Services that people with a recognised occupational disease are entitled to
In case of sick leave, medical care and daily allowances for the victim are taken in
charge.
In case of a permanent partial incapacity the victim gets compensation, either as a
unique compensation sum or as a regular pension, under the reserve of a possible reevaluation of the inability level. The compensation amounts depends on the level of
inability once the health state is at a stable level.
In case of death as a consequence of an occupational disease, the funeral costs are
reimbursed and the pension can be allocated to the persons being entitled to
receive them.
Page 10 – Limits of the studies conducted until now in agricultural environment
Why after more than 30 years of research, the risk of cancer in the agricultural
environment is not yet entirely understood and the role of occupational risk factors still
contested?
10
Limits linked to the lack of knowledge on the development of cancer
- The mechanisms of how a healthy cell develops into a cancerous cell are still poorly
understood
- The necessary time for cancer to develop in an organ is poorly understood and it
can be very long. Also, many dozens of years can pass between exposure to a risk
factor and the diagnostic of cancer can go by.
- There may be periods in life, where a person is more vulnerable to certain exposures
(childhood, puberty, menopause,…) and where these, even when moderated, can
have an effect on health.
Limits of studies conducted in agricultural environment
- Few studies of important size have been conducted. Hence, rare cancers in humans
(e.g. breast cancer in men) or in specific agricultural populations are not
investigated.
- The definition of occupational exposures has often been restricted to distinguish
agricultural workers from non-agricultural workers, without taking into account the
specificities of crop farming and animal husbandry, as well as related tasks;
- There were no precisions in the studies on pesticides used, even if there were more
than 1000 different molecules (around 300 today) with very variable toxicity;
- When studies concerned specific pesticides, farmers were often asked which
molecules they had used since the beginning of their career; remembering and
citing things like this by heart is complex and source of errors;
- Epidemiological studies conducted to date have only rarely considered women;
- Most of the studies have been conducted in North America and focused mainly on
insecticides and herbicides. Within the French context different molecules have been
used, in particular in case of herbicides and fungicides, to fight for instance plant
diseases on vineyards, cereals and orchards.
Page 11 – Routes of progress in the knowledge on the link between agriculture and cancer
To continue to make progress on this subject, it is necessary to conduct
epidemiological studies that are basically of two types: case studies and cohort
studies, both providing complementary data.
In France: the Agrican cohort
Cohort studies, such as the AGRICAN study set up in 2005 present many advantages.
They allow the examination of several diseases at once: more than 40 cancer types
and other diseases such as respiratory diseases, neurodegenerative diseases .... As
people can be interviewed more than once these studies also allow the tracking of
how exposures change.
Finally, cohort studies allow a targeted follow-up of people exposed to suspected risk
factors: those working in a farming environment rather than the general population.
11
In the US: agricultural health study
The AGRICAN study is not the only cohort study in the world being conducted in a
farming environment.
One other big agricultural cohort has been set up 20 years ago in two states of the
USA: Iowa and North Carolina. It is called “Agricultural Health Study”. This study
concerns the health of 52395 farm managers using pesticides in Iowa and North
Carolina (basically men) and 4916 professional operators (“applicateurs
professionels”) in Iowa. These people have been included in 1993 when they got their
licence to apply pesticides. This permit is comparable to the French Certiphyto but is
mandatory in the US since almost 30 years. The health of 32437 spouses of farm
managers is also monitored.
The outcome of the results of the Agricultural Health Study can be viewed at:
www.aghealth.nih.gov
Page 13 – The Agrican Cohort. The farming world and its risk factors
The first analysis of AGRICAN compared the health status of cohort members with the
one of the general population (mortality and cancer incidence). AGRICAN allowed for
the examination of an important diversity of cancers but also some sub-types (e.g.
blood cancer).
However, this comparison does not consider the differences in prevalences 3 of
established risk factors, such as smoking, which is less found in the farming
environment compared to the general public.
This analysis may therefore mask the effect of protective or risk exposures for certain
diseases. The conducted analysis compared the AGRICAN participants by taking into
account the risk factors established for the pathology at stake (age and smoking, for
instance).
It focused, to date, on agricultural activities related to the occurrence of bronchopulmonary cancer and two non-cancer respiratory diseases : chronic bronchitis and
asthma. Other cancer types are currently studied: prostate cancer, breast cancer,
bladder cancer and blood cancers.
Page 14 – The AGRICAN cohort – reminders
Between 2005 and 2007 you have received a questionnaire through your agricultural
health insurance organisation (“Mutualité Sociale Agricole” - MSA). This questionnaire
was sent to all members older than 18 years that year; that had paid their
membership fee since at least 3 years with the Mutualité Sociale Agricole and that
lived in one of the 11 departments covered by a general and/or special cancer
register. You belong to the 180000 participants that have accepted to complete and
send back this questionnaire.
3
Prevalence: status of health or of an exposure (here: smoking) of a population at a given time
12
Thank you for your participation
Your participation allowed us to produce the first results and to gain knowledge on:
- Your professional history
- Your farming activities (5 types of breeding and 13 types of crops) and the tasks that
you carry out (animal husbandry, milking, use of insecticides on animals, harvesting of
certain crops, use of pesticides on certain crops…)
- The equipment used to apply pesticides
- Your health (respiratory diseases, cardiovascular diseases, neurodegenerative
diseases etc.)
- Your life habits (smoking, food)
- Possible pregnancies, breastfeeding, … if you are a woman.
The stages of the cohort
After having received back your questionnaires, data have been entered into a
database (AGRICAN database). The health status of participants has been monitored
indirectly, by cross-checking the AGRICAN database with the cancer registers to
identify cancers that would have emerged in members since their inclusion in the
cohort; the CépiDC (the epidemiological centre for medical death causes) was used
to identify deceased people and the cause of their death within that period. These
data have allowed conducting some first analysis of the cohort.
The study goes now on with the distribution of the follow-up questionnaire, enclosed
within this second information bulletin.
Basic objective of the AGRICAN cohort: study the role of agricultural exposures with
regard to risk of cancer.
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Page 15 – Characteristics of the participants
Characteristics of the participants
There is a quite good balance between women and men, around 50% are retired
and an important majority of people work or have been working on a farm.
Activity sectors of participants:
88% from farms, (breeding and/or crops), 61% non-employees, 39 % farm employees,
12% “others”. “Others” are employees and non-employees working in the
cooperative sector, forestry, landscaping, tertiary sector etc.
Have participated in the AGRICAN study
Were retired
46% women
54 % men
45% men
55% women
Average age of the
participants
Average number of
years of subscription
at
MSA
for
all
participants
Average number of years of subscription at
MSA for all active participants
64 years
28 years
20 years
14
Page 16 – Health of cohort participants compared to the health of the general French
population
Are the death causes similar to the ones of the general public?
The collection of data on the entire French territory and the CépiDC’s encoding of
death causes allowed us to identify these.
We have one more year of additional follow-up data on mortality compared to
results presented in our first bulletin sent in 2011. The results are very similar, confirming
the longer life expectancy of the cohort members compared to the general
population.
Mortality by “important” causes
Cardiovascular diseases: the main cause of death within the AGRICAN cohort
30% of deaths in men
35 % of deaths in women
All causes taken together, men in the cohort had a 29% lower mortality rate than the
general population. In women, the mortality was 28% lower. These results confirm
findings in the last bulletin. This sub-mortality was observed for the majority of death
causes (see the detail in the table below).
Comparison of death causes in the AGRICAN cohort and the general population in
concerned departments, at equal age on a period from 2005-2010.
Death causes
men
women
Number of
deaths
Excess/deficit
(%)
Number of
deaths
Excess/deficit
(%)
Tumours
2971
-30
1585
-24
Endocrine diseases (diabetes,
…)
272
-33
256
-30
Digestive system (stomac
ulcer, cirrhosis,…
357
-35
208
-41
Mental affections (alcoholism,
depression, …)
151
-55
159
-54
Nervous system (Alzheimer
disease, Parkinson, …)
390
-38
382
-39
Circulatory system (heart
stroke infarction,
cerebrovascular accident …-
2706
-28
2279
-23
Respiratory system (flu,
pneumonia,….)
566
-38
356
-36
Urinary – genital system (renal
deficiency,…)
157
-36
93
-43
Skin affections (dermatosis,
hives…)
27
No
difference
25
-40
15
with general
population
Bone-artculation
(arthiritis, arthrosis,…)
system
66
No
difference
with general
population
59
-32
Infectious
diseases
and
parasitosis (tuberculosis, aids,
…
174
-26
107
-39
External
causes(accidents,
suicide, …)
584
-21
334
-25
Other death causes
665
No
difference
with general
population
800
No
difference
with general
population
All death causes
9086
-29
6643
-28
Page 17 – Mortality by cancer
The mortality rate by cancer is lower in the AGRICAN cohort than in the general
population
-31% of death in men
-24% of death in women
The risk of mortality through cancer is weaker in participants of the AGRICAN cohort
than in the general population, but the risk for breast cancer in men is increased by
37%. This result however is rather weak because of the low number of men with this
diagnosis.
Concerning other cancers not listed in the table, no significant differences have
been found between farmers and the general population.
Comparison of death caused by cancer in the AGRICAN cohort and the general population in
the concerned departments, at same age, between 2005-2010
men
Type of cancer
women
Number of
deaths
Excess/deficit
(%)
Number of
deaths
Excess/deficit
(%)
Cancers of the upper
respiratory-digestive system
(lips, mouth and pharynx)
63
-42
9
-51
Respiratory cancers (larynx,
trachea, bronchus, lung)
455
-49
101
-41
85
-40
19
No
Digestive cancers
Oesophagus
16
difference
with general
population
Liver and intrahepatic bile
pathways
211
-27
44
-36
Stomac
123
-17
59
No
difference
with general
population
Pancreas
153
-23
132
No
difference
with general
population
Colon
241
-28
172
-19
Rectum and anus
105
No
difference
with general
population
37
-44
Breast
14
No
difference
with general
population
230
-29
Prostate
429
-18
Bladder
105
-39
21
-48
Myelomes, leucemia,
lymphoma, …
312
-11
191
No
difference
with general
population
Other cancers
546
No
difference
with general
population
472
No
difference
with general
population
All cancers (malign tumours)
2842
-30
1487
-24
Cancers of the bladder and
reproduction organs
Blood cancers
Limits of the comparison of death causes
The differences of mortality between the general population and the members of
AGRICAN can reflect the differences of incidence4 , of screening or of exposure to risk
factors (or protection factors) present in the environment or in a professional
4
incidence of a disease is the number of new patients during a given period
17
environment. Differences can also be due to differences in prognostic (chances of
healing) after the diagnosis (the access to treatments and their efficacy).
The AGRICAN cohort has the objective to study the role of agricultural exposures.
Beyond mortality, it is important to also compare the incidence of diseases in the
AGRICAN cohort and the general population. Such an analysis can not only be
conducted on cancer pathologies as there are no registers in France for most of noncancer diseases such as respiratory diseases, Parkinson’s disease, or Alzheimer
disease.
Page 18 – Is the agricultural population more often affected by certain cancers than the
general population?
Persons in the AGRICAN cohort that were diagnosed with cancer are identified thanks
to the cancer registers. The occurrence of various cancer types within the cohort
have therefore been compared to the general population in the concerned
departments.
Cancers are more frequent in agricultural environment for the period 2005-2009.
Amongst the 43 cancer types, two appear to be more frequent in the agricultural
population than in the general population.
Skin melanoma in women:
+26 %
Multiple myeloma in men:
+26%
At this point in time of the follow-up, other cancers, such as blood and lip cancer
appear also to be more frequent, but these results remain to be confirmed:
Hodgkin lymphoma:
+19% for men and +38% in women
Certain types of non-Hodgkin lymphoma :
+3% to +32 % in women5
+6% to +22% in men6
Lip cancer
+49 % in men
Cancers that are less frequent in agricultural environments
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Lung cancers, mouth and pharynx cancers for both genders
Breast and rectum cancer in women
Colon cancer, bladder and liver cancer, pancreas and oesophagus cancer,
mesothelioma cancer and larynx cancer in men
Incidence of cancers in the AGRICAN population compared to general population
according to gender and at same age during the period 2005-2009 (number of
cases)
5
depending on type of lymphoma
6
depending on type of lymphoma
18
Page 19 – are these results confirmed by other studies?
Results of the American cohort
The American cohort confirms the lower incidence of cancers in agricultural workers
compared to the general public. This result is explained by:
- Less cancers linked to tobacco in a population with a small number of smokers (50%
less than expected)
However, the farmers in this cohort were more often affected by prostate cancer
(19% more than expected), blood cancers (for example: 20% more myeloma than
expected) and lip cancer (30% more than expected).
Women handling pesticides had a doubled risk of getting ovary cancer.
Many epidemiological studies concerning the risk of cancer in an agricultural
environment have been conducted worldwide during these last 30 years: North
America (US and Canada), Scandinavian countries, Italy. But to date, very little
studies have been conducted in the French farming community.
Results of studies conducted in other countries
As in AGRICAN, numerous studies have identified an increased risk for


skin melanoma
certain blood cancers (multiple myeloma, lymphoma, …)
lip cancer
On the contrary to the current AGRICAN results, other studies had identified excesses of
certain cancers:
19
-
prostate cancer
stomac cancer
nervous system cancer
Finally, a smaller incidence is confirmed for
-
cancers linked to smoking (lung, oesophagus, bladder)
cancers liked to food and/or physical activity (liver and colon)
breast cancer in women
Summary of international knowledge on cancers and farming
- Less frequent cancers in
farming environment
? poorly known cancers in
farming environment
+ more frequent cancers in
farming environment
Strongly linked to smoking:
- lung, bronchs, trachea
- oesophagus
- bladder
- pancreas
linked to food and/or
physical activity
- colon
- liver
Little or not linked to smoking
) breast (women and men)
kidney, rectum, testicles
ovary, cervix
connective tissue
Little or not linked to smoking
- blood: leucemia, myeloma
- ganglions: lymphoma..
- prostate
- brain
- skin
- lips
- stomach
Page 20 – skin cancer is more frequent in the farming environment
About 80,000 new skin cancers per year in France
70% of skin melanoma is caused by exposure to UV light
Types of skin cancer
Skin cancers are amongst the most frequent cancers. They are also among those
cancers that have most increased in frequency over the last 50 years.
Farmers and agricultural employees, strongly exposed to UVs, have more skin cancer
than the rest of the population.
The skin melanoma
More aggressive but less frequent, the number of skin melanoma has increased 5
times between 1980 and 2012. An early diagnosis allows the reduction of mortality
linked to this type of cancer.
Carcinoma
More frequent but less dangerous, it develops mostly on the uncovered parts of the
body (head and neck) after the age of 50.
Basic risk factors
Exposure to sun
The risk of contracting skin cancer is closely linked to exposure to sunlight
20
UVA and UVB light cause cancer, but their effect is not the same.
* UVA (most of UVlight) are responsible for immediate tanning and have a slight
potential to cause sunburn. They penetrate the deeper layers of the skin and can
cause premature aging of the skin.
* UVB are responsible for the skin tan that appears after several days after exposure
and cause sunburns. They are blocked by the epidermis and do not reach deeper
levels of the skin.
As farmers are often outside, they are regularly exposed to UV light, often without
protection.
At equal exposure to sun a person will have a different risk to develop skin cancer,
depending on the skin’s phototype (type of skin, number of beauty spots, personal or
family history of melanoma…)
Professional exposure
The use of pesticides containing arsenic in agriculture and viticulture (prohibited in
vineyards since 2001) and the use of PAHs are also risk factors. These occupational
exposures can also create synergies with exposure to UVs and the phototype and
cause skin cancer.
Characteristics
Reaction to sun
Recommendations in terms of
protection
Very white skin
Develops systematically sun
burns
No exposure, if possible
Blond or red hair
Blue or green eyes
Does not tan, gets red
Beauty spots
Clear skin
Frequent sunburns
Blond, dark blond or red hair
Does not tan easily or very
slowly
Blue to brown eyes
Remain in the shadow as
much as possible, don’t try to
get a suntan, never expose
skin to sun between 12 and
1600.
In the sun, maximum
protection: clothes, hat,
sunglasses, sun cream 50+
Sometimes freckles
Intermediate skin
Occasionally sunburns
Dark blond to brown hair
Tans gradually
Progressive and careful
exposure to sun
Avoid exposure between 12
and 1600
Brown hair
Brown skin
Sunburns are exceptional
Brown or black hair
Tans easily
Brown or black eyes
When exposed, high
protection recommended:
clothes, hat, sunglasses, sun
cream PF 30-50, or average
protection 15-25
Dark brown skin
Rare sunburns
Progressive exposure
Black hair
Tans easily
Avoid sun between 12 and
1600
Black eyes
Detect beauty spots with the ABCDE rule
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Wondering whether there is an effect of other pesticides is legitimate because the
main route of agricultural pesticides getting into the organisms is through the skin.
Getting checked regularly to detect melanoma and carcinoma in an early
stage
As for many cancers an early diagnosis helps to improve treatment: the chances of
healing increases and decreases the likelihood of keeping scares from various
treatments.
Protection
At times during the day where the sunlight is the most intense clothes are the most
efficient protection: hats, T-shirts with long sleeves, trousers … Not to forget to protect
your eyes with sunglasses!
The type of skin allows the categorisation of individuals according to the reaction of
their skin in case of exposure to sun
Monitoring and screening
Everybody can potentially develop a melanoma at every age. Regular selfmonitoring and participation in organized screenings are highly recommended.
Self-monitoring
How to make the difference between a simple beauty spot and a malignant
melanoma
- identify moles/nevus that are different from others
- being vigilant with regard to changes in shape, colour etc. (a new brown spot
appearing on your skin- the most frequent case) or a mole/nevus that changes
shape rapidly should alert you.
- Identify suspicious marks
Monitor regularly your marks with the ABCDE rule and see your physician without any
delay if you note changes.
Identify suspicious moles with the ABCDE rule
A
B
C
D
E
Screening
Asymetry
Borders
Color
Diameter
Evolution
Auto-screening
and annual
check by
dermatologist
Organised screening
To identify skin cancer at the earliest stage possible, the National Syndicate of
dermatologists and venereologists organizes every year together with the ministry for
22
health and the national institute for cancer (INCa) one entire day for free of charge
screenings. These usually take place in May every year.
Cancer info 0810 810 821
Page 22 – Respiratory diseases, cancerous or not
Identification of risk factors in the cohort
Even if there are other occupational exposures in the agricultural environment (dusts,
hydrocarbons, animal viruses…) the exposure to pesticides represents often the most
studied factor within epidemiological investigations.
Why is it important to investigate on the role of pesticides on health?
1 – Pesticides are almost all designed to have a toxic effect on a living organism
(plant, insect or a disease or a fungus). They are potentially dangerous products,
whose toxicity can’t be neglected, even if it changes from one product to the other.
2 – They are widely used in agriculture, particularly since the end of WWII. France
remains the most important farming country but also the country in Europe that uses
most pesticides.
Development of number of pesticide molecules authorized in France on 4 major
crops (source matrice PESTIMAT)
Wheat/barley
Viticulre
Maize
Apples
Number of active substance s authorised in France since 2000
152 on vineyards
150 on apples
128 on
wheat/barley
84 on maize
3 – Some pesticides persist for a long time in the environment and can accumulate in
our body (Organochlorine insecticides such as lindane or triazine herbicides such as
atrazine). To know more, deeper investigations are necessary on:
- The toxicity of molecules before being put on the market. The quality of the
authorisation dossier that is necessary for the marketing of the product is critical.
- On the populations that used these
products at a given time in their life,
regardless whether they are still active
today or retired.
Page 23 – Agricultural activities linked to
broncho-pulmonary cancers
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In the AGRICAN study almost 500 participants have contracted broncho-pulmonary
cancer, of which 82% were men.
Men: 90% were smokers
Women: 35% were women
AGRICAN confirms current studies, showing that there is a 20-fold risk of developing
broncho-pulmonary cancer in current smokers and in people smoking since more
than 40 years.
The risk factors of lung cancer in non-smoking women are not well understood
(passive smoking?) and the risks linked to their occupational exposures have been
little studied.
Which exposures could decrease the risk of broncho-pulmonary cancers?
Cattle and horse breeders
At same age and same smoking habits cattle and horse breeders having worked for
several decades in these stables have a twofold lower risk of developing bronchopulmonary cancer than other farmers, regardless of the size of the herd. A similar risk
reduction (2 times lower risk) was also suggested for sheep and milk goat breeders. It
remains a fragile conclusion though given the small number of diagnosis in these
breeders. The analysis did not reveal a risk decrease within pork or chicken breeders.
Breeding activities could well protect from lung cancer because they could expose
farmers to certain substances, for instance endotoxins. (Remark: the original French
sentence is: “Ces activités d’élevage pourraient protéger du cancer du poumon
puisqu’elles peuvent exposer les agriculteurs à certaines substances, notamment les
endotoxines”.
Decreased risks of the same order have also been found in other professional sectors
heavily exposed to these substances (dusts of cotton and micro-organisms in the
textile industry).
These AGRICAN data are in line with the rare studies conducted in other countries that
already suggested a decreased risk for these cancers in certain breedings. Thanks to
your participation, the AGRICAN cohort has allowed - for the first time - to provide
complementary and more solid data from a more complete questionnaire (kind of
breeding, number of work span necessary to reduce the risk etc.) than those
provided by existing studies on the possible protection effect of breeding activities
with regard to cancer . To date, all scientific data taken together could not yet come
up with a solid explanation of the protecting role of these substances against lung
cancer. These substances of microbial origin (in particular endotoxins) could however
increase the risk of respiratory diseases other than cancer (bronchial affection,
decreased respiratory function, toxic syndrome of organic dusts), as suggested by
AGRICAN for chronic bronchitis.
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Page 24 – Which agricultural exposures could increase the risk of developing bronchopulmonary cancer?
Fodder pea cultures
At same age and smoking habits the analysis showed that there is a two-fold higher
risk of contracting this cancer for those having worked more than 20 years in fodder
pea cultures, compared to other farmers. The harvest of fodder pea is linked to a 1,6
times higher risk. Another task that seems to increase the risk of developing this type
of cancer is tree trimming in orchards. However, to date we do not know which
exposures exactly (dusts, exposure to treated crops,…) could pose a risk on these
cultures (fodder pea and fruit tree growing).
Is exposure to pesticides linked to lung cancer?
The current analysis has not revealed an increased risk of developing lung cancer in
pesticide users, including in those being exposed for a longer time. We have however
not yet studied the effect of particular chemical families, nor specific molecules. This
analysis will therefore be refined over the coming months and years.
Agricultural activities linked to chronic bronchitis
This respiratory pathology is defined by coughing with expectoration during at least 3
months per year and since minimum 2 years.
In Agrican, about 8% of participants have declared suffering from chronic bronchitis
The main risk is smoking
- for men: 60% were smokers
- for women: 10% were smokers
Compared to non-smokers, the risk to develop this disease is multiplied by 2,5 in
current smokers and times 3 in smokers smoking since more than 40 years. The factors
explaining the development of chronic bronchitis in non-smokers are not all
understood. Passive smoking could be one of these factors, but also an occupational
cause, such as for lung cancer.
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Page 25 – Which agricultural exposures could increase the risk of developing chronic
bronchitis?
Cattle breeding
This risk would be increased in cattle breeders having worked more than 20 years on
less than 20 cattle. These workers had a 1,5 times risk of developing this pathology.
This exceedences could be caused by the exposure to micro-organisms present in
the cattle stables. They could be of bacterial of fungal origin. The work on small herds
could reflect traditional farms (typically smaller buildings than more recent farms). The
AGRICAN results are in line with other epidemiological studies conducted on this
pathology in France (studies coordinated by Pr Jean-Charles Daphin in the Doubs
department) or more generally in European studies.
Potato cultures
The analysis have also stressed an increased risk in potato producers, in particular
those having worked on these crops since more than 20 years and on more than 20
ha (3-fold risk). The exposure to pesticides on this crop would multiply by 1,6 the risk of
developing this disease. These results would need to be confirmed because this
professional sector has been little studied. One single study is indeed not sufficient to
conclude on “risk” exposures.
Pesticide poisonings
The AGRICAN participants that have responded that they have already been
poisoned with pesticides have a 1,6 –fold risk to develop chronic bronchitis.
Agricultural activities linked to the risk of developing asthma
In AGRICAN, around 8% of the participants have declared suffering from asthma.
Which agricultural exposures could increase the risk of developing allergic asthma?
26
Pesticides
The use of pesticides during professional life in viticulture, fruit tree growing or on
meadows would increase the risk of developing allergic cancer by 1,3-1,6.
Pesticide poisoning
Agrican participants that declared having been poisoned by pesticides had a 2-fold
risk of developing allergic asthma.
Horse breeding
The risk was multiplied by 1,4 in horse breeders.
Certain crops
Increased risks have been found for sugar beet crops (1,5-fold risk) and greenhouses
(1,7- fold)
Page 26 – perspectives 2015-2016
1 – We will finalize the first phase of exposure monitoring based on the follow-up
questionnaire that you just received.
2 – We will study (as for lung cancer) risk factors (but also potential protection factors)
for cancers linked to farming professions (prostate cancer, breast cancer, bladder
cancer and blood cancer)
3 – For all cancers we will study the use of particular pesticides (chemical families and
molecules that are particularly often used now or in the past in France- related to
cancers.
The pesticides
We will select pesticides that are the most used in French farming and also those for
which an American study shows currently an increased risk.
This American study is restricted to about 50 molecules, chosen mostly because of
their predominant current or past use in concerned states. Most of these molecules
had been authorized in France. 18 of them are still authorized today.
Pesticides studied in the American study:
Herbicides
Insecticides
Fungicides
Fumigants
Alachlor
Aldicarb
Benomyl
Aluminium phosphide
Atrazine
Aldrin
Captan*
Ethylen dibromide
Butylate
Carbofuran
Chlorothalonil*
CCl14/CS2
Chlorimuron ethyl
Carbaryl
Maneb/Mancozeb*
Methyl bromide*
Cyanazin
Chlordane
Metalaxyl*
Dicamba*
Chlorpyrifos*
Zirame*
2,4-D*
Coumaphos
EPTC
Dichlorvos*
27
Glyphosate*
Diazinon*
Imazethepyr
Dieldrin
Metolachlor
DDT
Metribuzin*
Heptachlor
Paraquat
Lindane
Pendimethalin*
Malathion*
Paraffin oil*
Parathion
2,4,5 T
Permethrin
2,4,5 TP
Phorate
trifluraline
Terbufos
Toxaphen
Trichlorfon
* still authorised in France
Page 27 – financing of projects in agricultural environment, conducted by the cancer &
preventions team
Our research team conducts various health research projects in the agricultural
environment, an important part of our budget is used to conduct AGRICAN.
The other studies
On the exposure to pesticides, in order to determine who is exposed and at to level:
1 - During application on crops but also in breedings (exoparasite treatments) and
during contacts with treated crops (PESTEXPO study: measures in the field on working
gear for farmers);
2 - To establish the link between the use of pesticides on a specific crop and the
likelihood of use of a specific pesticides (PESTMAT study).
On the impact of farming activities on the early effect biomarkers
Other epidemiological studies (type: case-study) (for instance on brain cancers)
The financials in our projects
Between 2005 (creation of the AGRICAN cohort) and 2014, our sponsors were:
- (25% of our work): the State through ONEMA, ANSES and INCA
- (25%) various associations of which the Anti-Cancer ligue
- the MSA (about a fifth of the sum)
- (about a third: other public finances, such as Univerisity of Caen, local collectives) or
private (Centre against Cancer F Baclesse and UIPP)
For each financial, be it private or public, the established convention with our unit
includes that the financial is informed on our scientific conduct of the launched
28
project, but that it also has no right to look at the obtained results and claim property
rights.
Page 28 - Glossary
Farmers
Within AGRICAN, farmers include non-employees (managers, co-managers etc.) but
also employees if they work on farming businesses
Case-studies
Epidemiological study based on the questioning of patients and healthy people to
study the effect of certain exposures
CEPIDC
Centre of Epidemiology on medical causes of death (Centre d’Epidemiologie sur les
causes médicales de décès)
Cohort
Group of people whose health state and their exposures are followed over time
CRRMP
Regional committee of the recognition of professional diseases (Comité Régional des
Maladies Professionelles)
Epidemiology
Epidemiology is the study of factors influencing health and population diseases
Francim CRNce Cancer Incidence Mortalité
Association law 1901 grouping French cancer registers
Incidence
The incidence of a disease is the number of new patients during a given time
29
Prevalence
In epidemiology the prevalence is the measure of the frequency of the health of a
population at a given moment (e.g. the prevalence of chronic bronchitis-) but also
the proportion of concerned people by the exposure (e.g. prevalence of smoking)
Page 29 – Organisation and functioning of the AGRICAN cohort
The steering committee
The AGRICAN cohort has a steering committee comprising members of the research
team Cancers & Preventions at Caen” and members of the Laboratory Professional
health at Bordeaux , the local and central funds of the MSA and the cancer registers
FRANCIM. This committee meets at least twice per year since 2004.
The members of the scientific council
The way to proceed of the AGRICAN cohort is based on the opinion of an international
scientific council composed of 8 members:
Laura Beane-Freeman
Coordination of the AHS cohort in the USA
Aaron Blair
National Cancer Institute in the USA
Françoise Clavel
INSERM, coordination of the E4N cohort
Jacqueline Godet
President of the Ligue Contre le Cancer
Serge Hercberg
University of Paris 13, coordinator of the Nutrinet study
Nicole Le Moual
INSERM, team “professional and domestic risks in respiratory epidemiology”
Kurt Straif
Center International de Recherche sur le Cancer
Paule Vasseur
University of Metz, environment toxicologist
Your data will remain strictly confidential
Anonymity
The AGRICAN investigation has been approved by the Consultative committee for
processing data related to health (CCTIRS) and the National Committee on
informatics and freedom (CNIL).
30
We remind you that the collected data are processed in a strictly anonymous way.
The responses to questions are strictly confidential. They are used in grouped statistics
that do not allow the identification of people.
The researchers, as the researchers conducting the analysis, have signed for
professional secrecy. There is no possibility for a third party to establish the link
between responses and the identity of a person.
In line with the law “informatics and freedom” you can exert your right to access and
correct your data with Dr Pierre Lebailly, coordinator of the study. You can contact
him on:
Centre François Baclesse
Avenud Général Harris
14076 CAEN Cedex 05
31