Cancer in offspring of parents engaged in agricultural activities in Norway: incidence and risk factors in the farm environment.
ABSTRACT In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952-1991 to parents identified as farm holders in agricultural censuses in Norway in 1969-1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965-1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89-5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63-6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity.
- SourceAvailable from: infomed.sld.cu
Article: MEDIOAMBIENTE Y CÁNCER[Show abstract] [Hide abstract]
ABSTRACT: RESUMEN Se exponen brevemente algunos factores medioambientales capaces de convertirse en elementos cancerígenos para el hombre, entre ellos el tabaco, el alcohol y ciertos tipos de alimentos, así como también determinados tóxicos industriales y el estrés como mecanismo psi-cológico, que pueden modificar la vigilancia inmunológica y favore-cer la aparición y desarrollo acelerado del cáncer, al actuar sobre los linfocitos y las interleucinas. Estos aspectos deben servir para ga-rantizar una eficiente promoción de salud, encaminada a prevenir tan terrible enfermedad. Palabras clave: CARCINÓGENOS AMBIENTALES; PROMOTORES DE TUMOR; ONCÓGENOS; VIGILANCIA INMUNOLÓGICA; SUSTANCIAS NOCIVAS. =================== INTRODUCCIÓN El cáncer es un padecimiento tan temido como antiguo, 1 que continúa siendo hoy, en los albores del siglo XXI, una incógnita para el hombre. La ciencia ha dedicado innumerables esfuerzos para esclarecer la verdadera gé-nesis de este proceso, y aunque a través de los años se ha avanzado en su estudio, no ha sido con la rapidez y dinámica que pre-cisa. El primer intento para explicar las cau-sas de la enfermedad se sustentó en la gran incidencia de cáncer de pulmón en fumado-res, así como en la asociación de la neopla-sia maligna de vejiga con componentes de las pinturas; es decir, se insistió funda-mentalmente en los factores externos como desencadenantes de la afección. 2, 3 Con el proceso de la genética se co-menzó a ampliar el horizonte investigativo y se descubrió la existencia de oncogenes en el genoma de células tumorales, por lo cual se pensó lógicamente: "el enemigo está dentro de uno mismo", y durante mu-cho tiempo el hombre se sintió aún más temeroso, pues cualquiera podía hallarse marcado irremediablemente por sus propios genes para padecer el mal. 2, 4 Afortunadamente ya se conoce mucho más sobre los agentes que condicionan la aparición del cáncer, aunque todavía no al-canza la expectativa deseada: el problema estriba en la combinación de factores del medio externo, que influyen sobre los on-cogenes y alteran la secuencia de creci-miento y desarrollo de las células. 3 -6 Con este descubrimiento, el hombre ha empezado a ganar la batalla contra el cán-cer (la influencia de la polución, los pro-ductos enlatados y el estrés, entre otros, pueden ser perfectamente controlados) y su conocimiento ayudará a evitar uno de los peores sufrimientos del ser humano. En este trabajo nos propusimos mencio-nar algunos elementos carcinogénicos pre-viamente conocidos y otros de más reciente hallazgo, con el fin de hacer un modesto aporte a la lucha mundial contra esta do-lencia.
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ABSTRACT: The contribution of occupational exposures to rare cancers, which represent 22% of all cancers diagnosed annually in Europe, remains insufficiently considered. We conducted a comprehensive review of occupational risk factors in 67 rare cancers (annual incidence <6/100,000). An examination of relevant articles in PubMed (1960–2012) and the International Agency for Research on Cancer (IARC) monographs revealed that 26 cancer sites, such as mesothelioma, nasal, larynx, liver, ovarian cancer, bone sarcoma, and hematopoietic malignancies were consistently linked to occupational factors. Main exposures included asbestos, wood dust, metals/metalloids, formaldehyde, benzene, vinyl chloride, and radiation. There was inconsistent evidence regarding 22 rare malignancies. We did not identify relevant data for 19 rare cancers. Despite limitations of published evidence, our review provides useful information that can facilitate the identification of work-related factors that contribute to rare cancers. International collaborations, development of improved exposure assessment methods, and molecular approaches can improve future studies.Critical reviews in oncology/hematology 01/2013; · 5.27 Impact Factor
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ABSTRACT: Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle-related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non-coding RNAs are viable mechanistic candidates for a non-genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health-related effects in future generations.BioEssays 01/2014; · 4.84 Impact Factor
Znt. J. Cancer: 65,39-50 (1996)
0 1996 Wiley-Liss, Inc.
CANCER IN OFFSPRING OF PARENTS
ACTIVITIES IN NORWAY: INCIDENCE
Publication of the International Union Against Cancer
Publication de I’Union Internationale Contre le Cancer
ENGAGED IN AGRICULTURAL
AND RISK FACTORS IN THE
‘National Institute of Occupational Health, Oslo; 2Cancer Registry of Norway, Oslo; 3Medical Birth Registry o f Norway,
University o f Bergen, Bergen; 4Statistics Noway, Kongsvinger; and SNowegian Crop Research Institute, Plant Protection Centre, As, Noway,
Lorentz M. IRGENS3, Anne S. BYE4 and Leif sUNDHEIM5
In this study of cancer in offspring we demonstrate that
factors linked to horticulture and use of pesticides are associ-
ated with cancer at an early age, whereas factors in animal
husbandry, in particular poultry farming, are associated with
cancers in later childhood and young adulthood. Incident cancer
was investigated in offspring born in 1952- I99 I to parents
identified as farm holders in agricultural censuses in Norway in
1969- 1989. In the follow-up of 323,292 offspring for 5.7 million
person-years, 1,275 incident cancers were identified in the
Cancer Registry for 1965-199 I. The standardized incidence for
all cancers was equal to the total rural population of Norway,
but cohort subjects had an excess incidence of nervous-system
tumours and testicular cancers in certain regions and strata of
time that could imply that specific risk factors were of impor-
tance. Classification of exposure indicators was based on infor-
mation given at the agricultural censuses. Risk factors were
found for brain tumours, in particular non-astrocytic neuroepi-
thelial tumours: for all ages, pig farming tripled the risk [rate
ratio (RR), 3. I I ; 95% confidence interval (Cl), I .89-5.I3];
indicators of pesticide use had an independent effect of the
same magnitude in a dose-response fashion, strongest in chil-
dren aged 0 to 14 years (RR, 3.37; 95% CI, l .63-6.94). Horticul-
ture and pesticide indicators were associated with all cancers at
ages 0 to 4 years, Wilms’ tumour, non-Hodgkin’s lymphoma, eye
cancer and neuroblastoma. Chicken farming was associated
with some common cancers of adolescence, and was strongest
for osteosarcoma and mixed cellular type of Hodgkin’s disease.
The main problem in this large cohort study is the crude
exposure indicators available; the resulting misclassification is
likely to bias any true association towards unity.
o 1996 Wiley-Liss, Inc.
Reviews on childhood cancer (e.g., Savitz and Chen, 1990)
have not firmly established parental occupational exposures as
causal factors. In studies of parental occupation in which all
sites in childhood have been the end-points (Zack et al., 1980;
Sanders et al., 1981; Hemminki et al., 1985; Olsen et al., 1991),
the risk estimates for children of farmers or agricultural
workers have not deviated much from the null.
Nevertheless, in several case-control studies brain tumours
in childhood have been associated with parental farming
(West, 1988; Wilkins and Koutras, 1988; Wilkins and Sinks,
1990; Kuijten et al., 1992; Bunin et al., 1994), and environmen-
tal risk factors in farming are considered to be of particular
interest (Kuijten and Bunin, 1993). Both contact with animals
and exposure to pesticides have been suspected as risk factors.
Parental exposure to pesticides has been associated with brain
tumours in several studies (West, 1988; Sinks, 1985; Davis et
al., 1993; Bunin et at., 1994), and Leis and Savitz (1995) found
an association with the use of pest strips in the home. Gold et
al. (1979) found increased odds ratios for contact with sick pets
and use of insecticides in the home, but the results were not
confirmed in a later study (Howe et al., 1989). In another study,
contact of either the mother (McCredie et al., 1994a) or the
child (McCredie et al., 1994b) with animals was not associated
with brain tumours.
Apart from an increased odds ratio for acute leukaemia seen
among the children of mothers in agricultural work in Shang-
hai (Shu et al., 1988), there have been few indications that
parental occupation as a farmer poses a risk for leukaemias
(Van Steensel-Moll et al., 1985; Lowengart et al., 1987).
Parental exposure to pesticides has also been associated with
increased occurrence of leukaemia, mainly acute (Lowengart
et al., 1987; Laval and Tuyns, 1988; Shu et al., 1988; Buckley et
al., 1989; Buckley, 1992; Leiss and Savitz, 1995). Immunologic
and infectious mechanisms have been hypothesized for child-
hood leukaemias, and the analogy to malignancies seen in
adult farmers is of interest: immunologic mechanisms trig-
gered by pesticides or animal antigens are suspected to be
important for the development of leukaemias among adult
farmers, oncogenic zoonotic viruses being among the sus-
pected agents (Blair et al., 1992).
Reports concerning an association between testicular cancer
and agricultural exposures are conflicting (Blair et al., 1992).
Testicular cancer is suspected to be related to high foetal levels
of free oestrogen, and organochlorine pesticides and other
oestrogenic compounds have been suggested as causative
agents (Sharpe and Skakkebxk, 1993).
Pesticide use in the home has also been associated with
childhood lymphoma and soft-tissue sarcoma (Leiss and Savitz,
1995). The implication of phenoxy-acid herbicides as a cause of
soft-tissue sarcomas and lymphomas in adults (Blair et al.,
1992) is also of interest, since these malignancies are relatively
common in childhood and adolescence.
To investigate cancer incidence and reproductive outcomes
in the offspring, we established through linkage between
several registers a national cohort of families in Nonvegian
agriculture. Our hypotheses comprised an excess of sarcoma,
leukaemia, lymphoma, testicular cancer, and particularly ner-
On the basis of earlier reports, a number of hypotheses were
formulated about indicators of exposure and specific groups of
malignancies: exposure to animals or pesticides and brain
tumours (Gold et al., 1979; West, 1988; Wilkins and Koutras,
1988; Wilkins and Sinks, 1990; Kuijten et al., 1992; Bunin et al.,
1994); exposure to animals (in particular dairy cows and
chickens) or pesticides and acute leukaemia (Lowengart et al.,
1987; Laval and Tuyns, 1988; Shu et al., 1988; Buckley et al.,
1989; Buckley, 1992; Leiss and Savitz, 1995); exposure to
pesticides (in particular organochlorine pesticides commonly
used in horticulture) and testicular cancer (Sharpe and Skak-
kebaek, 1993); exposure to pesticides (in particular herbicides
in forestry and grain farming) and soft-tissue sarcoma and
lymphomas (Blair et al., 1992; Leks and Savitz, 1995).
In general, the potential causative agents were considered to
act either during the pre-conceptual period through the
father’s maturing germ cells, during pregnancy via the mother,
or directly in early infancy. If pesticides applied seasonally
6To whom correspondence and reprint requests should be sent, at
National Institute of Occupational Health, P.O.B. 8149 Dep, N-0033
Oslo, Norway. Fax: i 4 7 22 603276.
Received: June 14,1995 and in revised form August 29,1995.
cause cancer by acting on the father's maturing germ cells, an
uneven distribution by month of birth would be anticipated for
the malignancy in question. In particular, we suspected that a
paternally mediated effect of pesticides applied during spring
and early summer (as in grain farming and in orchards in
Norway) would be strongest for children born during spring.
MATERIAL AND METHODS
Statistics Norway have held national agricultural censuses
resulting in computerized information files in 1969, 1979, and
1989, and horticultural censuses in 1974 and 1985. The criteria
for participation have changed slightly over time. The 1969
census included all farms comprising an agricultural area of at
least 0.5 hectare (ha); the 1979 and 1989 censuses combined
agriculture and forestry and included both farm holdings with
a productive forest area of 2.5 ha or more and farms smaller
than 0.5 ha which met certain criteria with regard to livestock
size, area of greenhouses, fields for vegetables or berries, and
number of fruit trees. The inclusion criteria for the horticul-
tural censuses covered area of greenhouses, field-grown veg-
etables or berries, or number of fruit trees. Participation in the
agricultural and horticultural censuses was mandatory, and is
considered to be complete, since governmental subsidies to
farm holdings were conditional on this information.
All personal farm owners at any of the censuses who were
born after 1924 were identified by the personal identity
number assigned to all residents of Norway. Subtraction of
duplicates (5.1 percent; owners of more than one farm at a
single census) yielded 149,254 farm holders (125,873 males,
23,381 females). Individuals owning more than one farm were
assigned to the place of residence.
After linkage of the file of farm owners with the Central
Population Register 334,135 offspring born in 1940-1992 were
identified. The Central Population Register was established in
October 1964 and is based on information from all residents of
Norway at the time of the 1960 population census and on
continuous updating since 1964 (Brunborg and Kravdal, 1986).
Linkage of parents and children is possible because each
record in this register includes both personal identification
numbers. Parental identification was included prospectively at
birth for children born after October 1964; for children born
earlier, parental identification was included in retrospect at
the population census in November 1970. This was complete
only for children born after 1951. Records of children born
before October 1964 and who died before the 1970 census do
not include the parental identification number (Brunborg and
The present study included all 323,359 offspring born
between 1952 and 1991 who were followed up for incident
cancer in the Cancer Registry of Norway. Children born
between 1952 and 1964 were followed up from 1971, as earlier
start of follow-up would have led to a negative bias due to lack
of identification of children who died before the 1970 popula-
tion census. Children born after 1964 were followed up from
birth. All children were followed up through 1991, or until
death or emigration. Linkage with the Cancer Registry was
complete, and only 67 children who either died or emigrated
before the start of follow-up in 1971 did not contribute
person-time. In total, 102,055 children born between 1952 and
1964 and 221,237 children born between 1965 and 1991 were
followed up for 5,696,606 person-years (Table I).
Information about the farm holding given at one or several
agricultural censuses was assigned to the records of all mem-
bers of the holder's family. Since 83% of the population came
TARLE I - UISI'KIBUTION OF ('IIARACrEKISI'ICS AMOK(; OFFSPRING
(n = 323.292; j,hY6.606 PERSON-YEARS) BORli I S IYS?-IYYl TO PARESTS I S
AGRI('IJI.TlJRAI. WOKK ACCORDING TO TIIF: UOKWEGIAU
AGKICULICRAL. CENSUSES I S IOOY-lY8Y
Year of birth
Census closest to birth date
Potatoes ( 2 0.1 hectare)
No farming activity3
Pesticide spraying equipmentS
Main income from farm holding
Either parent working 2500 hr annual on farm
Father working outside farm holding
Mother workiig outside farm holdiig
Either parent with agricultural education
'On the farm at the census closest to the year of birth. Children
from farms with several activities at the census contributed
person-time in all those activities.-21nformation only in 1969, 1979
and 1989 censuses (0.3% mis~ing).-~Children from holdings with
no animal farming, horticultural activity or grain farming at the
census closest to the year of birth.-41nformation only in 1969
census (24.9% mis~ing).-~Information only in 1979 census (7.1%
CANCER IN OFFSPRING OF FARMERS
from family holdings, information from the same farm holding
was included even in censuses held before the child’s parent
took over. This resulted in 1969 census information for more
than 75% of the children. Information from the 1979 and 1989
censuses was available for more than 90%, while information
from the horticultural censuses in 1974 and 1985 was available
only for a few percent (Table I). The information included:
location (municipality) of the farm holding and whether it was
the residence of the holder; farming area and area used for
cultivation of potatoes, different types of grain, field veg-
etables, greenhouses, and forestry; number and species of
livestock; number and species of fruit trees and berries grown;
horses, tractors, source of water (1979), use of silage, and use
of fertilizers (1979, 1989); amount of money spent on pesti-
cides in the preceding year (1969), and pesticide spraying
equipment on the farm (1979); time spent on agricultural work
on the farm and work outside the farm for both parents;
fraction of total family income from the farm; agricultural
education of holder or spouse; year of conveyance of the farm
holding (1979,1989); and whether a family farm (1979).
The exposure indicators and their distributions are given in
Table I. The main types of farming in Norway are animal
husbandry, horticulture, and grain farming. More than one
type of farming was commoner on the holding early in the
study period, and specialized production and monoculture
became more prevalent in the later periods. Norwegian farms
were mostly small and operated by the family members.
Usually, 3 generations lived on the holding, and the children
(mostly sons) took over when the parents were too old to
operate the farm. The distribution of other explanatory vari-
ables in Table I indicates that a large proportion of the
holdings were part-time enterprises, and part-time employ-
ment outside the holding was more commonly reported in the
later censuses. The criteria for participation in the agricultural
censuses are loose, and only 58% of the offspring came from
holdings where either parent worked for at least 500 hr
annually, which is the standard criterion for a farmer in
population censuses given by Statistics Norway (Central Bu-
reau of Statistics, 1975). This sub-set of the cohort is termed
For the majority of holdings, information was available from
all 3 agricultural censuses. We considered census information
for the pre-conception period, during pregnancy and in infancy
most relevant in this study of early cancers and, therefore,
defined the census closest in time to the child’s birth as the
index census, but indicators of pesticide use, water source, and
fertilizers were included when available, even for non-index
censuses. The index census of the oldest children took place
during their adolescence or even in adulthood. For those born
between 1952 and 1964, the age at the time of the index census
was over 10 for 50% and over 20 for 10%. For 81% of children
born between 1965 and 1991, the gap between birth and the
index census was 5 years or less.
Most of the exposure indicators were quantified in catego-
ries, but they were analysed as dichotomies (present/absent),
on the assumption that contact and exposures are as likely to
be high for small-scale activities where work practices are more
manual. Money spent on pesticides in 1968 was categorized in
4 groups: none; NOK 1-99; NOK 100-499; and NOK 500 or
more. Sub-types of horticulture (except field vegetables) were
uncommon, so orchards and greenhouse cultivation were
combined (7% of offspring exposed).
The outcome classification was based on the information on
cancer site and morphology in the Cancer Registry of Norway.
Case reporting to the Registry has been mandatory since 1952.
Brain neoplasms and acute leukaemias were each grouped in
order to ensure robust categories; neuroepithelial brain tu-
mours were categorized according to Kleihues et al. (1993) as
astrocytomas and non-astrocytic neuroepithelial tumours; acute
leukaemias were grouped as lymphocytic, myelocytic and other
types. Hodgkin’s disease was divided into nodular sclerosis and
the mixed cellular type.
The analyses were performed with the “Epicure” statistical
software program (Preston et al., 1993). Two analytical meth-
ods were applied: indirect standardization (observed over
expected cases) with an external reference population; and
Poisson regression modelling with reference groups within the
Cancer morbidity was investigated by comparing the ob-
served and expected numbers of cases. The expected numbers
of cases were estimated from the person-year experience in
different strata, and the 5-year age- and gender-specific rural
rates in Norway for each year from 1965 through 1991. The
rural population comprises residents outside towns, which was
57% of the total population in 1980. Gender-specific standard-
ized incidence ratios (SIR) were calculated for all cancers and
for cancers at specific sites for the study population; sub-set
analyses were performed for offspring with a parent who
fulfilled the occupational criterion for a farmer. Strata of age
intervals, period of follow-up, year of birth, and geographical
regions were also investigated. Ninety-five percent confidence
intervals (CI) were computed under the assumption of a
Poisson distribution of the observed cancers under the null
The associations between exposure indicators and specific
cancers were assessed in Poisson regression. The main mea-
sure of association was the ratio of incidence rates (rate ratio,
RR) between subjects with the exposure indicator in question
and subjects without the exposure indicator. RR estimates
were adjusted for age and calendar year, or birth year and
calendar year. Other exposure indicators and explanatory
variables were included in the models if they altered the RR
estimates by more than 15%. We calculated 95% CI, and those
that did not include unity were considered statistically signifi-
cant. For the pesticide purchase indicator, we performed a test
of trend for the association between expenditure level and
cancer whenever the number of cases were sufficient.
The relevance of the information obtained from the index
census was judged on the basis of a prion’ criteria in order to
identify offspring who were most likely to have spent the first
years of their life on a farm. Information was considered
“relevant” if either parent was the farm holder at the time of
the index census and lived on the farm. Information was also
considered “relevant” if the farm holder was closely related to
the parents and was living at the farm, and either parent took
over the farm at a later census. According to this definition,
information was “relevant” for 70% of the study subjects. In
the analyses of cancer risk at age 0 to 4 years and in analyses of
infant tumours (Wilms’ tumour, eye cancer, hepatic cancer,
neuroblastoma), information was considered “relevant” only if
the gap between birth and index census was 5 years or less, in
addition to the other criteria. An increased stronger exposure-
outcome association for this sub-set or the sub-set of offspring
of parents who fulfilled the occupational criterion for a farmer
strengthened the assumption of a true association.
A total of 1,275 incident cases of cancer was identified in the
follow-up. The distribution for selected sites are provided in
Table 11. Brain tumours (ICD-7 193.0) counted 182 cases, of
TABLE I1 - STANDARDIZED INCIDENCE RATIOS FOR ALL CANCERS AND CANCERS AT SELECTED SITES
AMONG OFFSPRING BORN 1952-1991 TO PARENTS IN AGRICULTURAL WORK, ACCORDING TO THE
NORWEGIAN AGRICULTURAL CENSUSES 1969-1989, AND AMONG OFFSPRING OF A PARENT WHO
FIJLFILLED THE STANDARD OCCUPATIONAL CRITERION FOR A FARMER
(WORKING 2500 HR ANNUALLY ON A HOLDING)
Cancer site (ICD 7)
Total study population’ Farmers’ offspring2
SIR 95%CI 95%CI
A 1 1 sites (140-209)
Cervix uteri (171)
Nervous system (193)
Endocrine glands (195)
Connective tissue (197)
Hodgkin’s disease (201)
Non-Hodgkin’s lymphoma (200,202)
Unspecified and other sites
In = 323,292; 5,696,606 person-years.-*n = 188,680; 3,323,876 person-years.
which 76 were classified as astrocytomas and 65 as non-
astrocytic neuroepithelial tumours. Nearly all leukaemias were
acute: 92 lymphocytic, 36 myelocytic, and 35 of other types.
Cases of nodular sclerosis numbered 37 and of the mixed
cellular type of Hodgkin’s disease, 34. There were 29 cases of
osteosarcomas, 27 neuroblastomas, and 17 Wi1ms’-tumour
The SIR for cancer at all sites was close to that expected,
and no site-specific SIR deviated significantly from unity
(Table 11). Few breast cancers and cervical cancers were
reported in comparison with the numbers expected. Among
the major sites, non-significant elevations of the SIR were
found for testicular cancer, bone cancer, and Hodgkin’s
disease. For nervous-system tumours, the SIR was 106 (9.5%
The 188,680 offspring of farmers (either parent worked at
least 500 hr annually on a farm) had 739 incident cancer cases
and a SIR close to unity (Table 11). This sub-group had SIR
that deviated more markedly from unity for several sites: SIR
were elevated for testicular cancer, nervous-system tumours,
Hodgkin’s disease, bone cancer and ovarian cancer, but
significantly only for testicular cancer.
Table I11 provides results for all cancers by gender in strata
relating to time and geographical location of the farm. The
SIR was decreased for females and slightly increased for
males. This gender difference was due mainly to increased SIR
for males in the 5- to 14-year age group; the SIR estimates for
females were decreased for all ages except 0 to 4 years,
strongest during attained age of 15 to 19 years. No specific SIR
trends were apparent in different periods of follow-up; a
moderate increase of borderline significance was found for
males during 1985-1991. Moderate increases in the SIR for
both genders were found for offspring born during 1980-1991:
the SIR for boys and girls combined was 119 (95% CI, 96-148).
The SIR differences for all sites in males and females in
adulthood were due to some sex-specific sites (testicular
cancer, breast cancer, cervical cancer). The gender difference
of SIR in childhood was due to several sites, mainly nervous-
system tumours, bone cancer and leukaemia (data not shown).
The space-time variations in SIR were investigated for
specific major sites. Some of the deviations in Table 111 were
due to clustering of nervous-system tumours and testicular
cancer. Thus, during follow-up 1985-1991, 115 nervous-system
tumours were diagnosed (SIR, 128; 95% CI, 106-154). In this
period, 45 cases were diagnosed in the 0- to 14-year age group
(SIR, 149; 95% CI, 108-199), of those, 13 cases came from a
farm holding in the southern region (SIR, 256; 95% CI,
136-438). The testicular-cancer-incidence excess was confined
to the western region, particularly at age 15 and older and for
boys born between 1952 and 1969 (50 observed cases; SIR, 167;
95% CI, 125-218). Forty of those cases were observed among
farmers’ sons (either parent working at least 500 hr annually
on the farm); the SIR was 216 (95% CI, 156-290). Similar
clusters in leukaemias or lymphomas were not apparent.
The incidence of cancer at all sites during the first years of
life was associated with horticulture and pesticide indicators,
whereas cancer later in life was related to contact with animals,
in particular chickens (Table IV). For ages 0 to 4 years (total
201 cancer cases; 1,045,535 person-years), offspring on farms
with orchards or greenhouses had a nearly doubled RR; the
association with pesticide purchase showed a dose-response
relationship for different levels of expenditure, but the test for
trend was not significant ( p = 0.12). For ages 5 to 19 years
(total 403 cancer cases; 3,133,341 person-years) increased RR
were found for exposure to chicken farming.
Brain tumours were the commonest neoplasm (Table V). A
RR of 1.59 for brain tumour was found in association with pig
farming, while the increases were more moderate and non-
significant for chicken farming, grain farming, horticulture and
pesticide purchase. The increases were restricted mainly to the
group of non-astrocytic neuroepithelial tumours, especially for
pig farming, pesticide purchase and chicken farming; for
pesticide purchase the RR increased for increasing expendi-
ture levels (test for trend, p = 0.0002). When all exposure
indicators were included simultaneously in a model, the effects
of grain farming and horticulture on the risk for non-astrocytic
neuroepithelial tumours were dependent on pesticide pur-
chase, whereas pig farming (RR, 2.48; 95% CI, 1.37-4.50) and
CANCER IN OFFSPRING OF FARMERS
TABLE Ill - GENDER-SPECIFIC STANDARDIZED INCIDENCE RATIOS FOR ALL CANCERS FOR SPECIFIED
REGIONS AND TIME PARAMETERS AMONG OFFSPRING BORN 1952-1991 TO PARENTS IN AGRICULTURAL
WORK ACCORDING TO THE NORWEGIAN AGRICULTURAL CENSUSES 1969-1989
Males (n = 166,291;
Females (n = 157,001;
Attained age (years)
Period of follow-up
684 104 97-112 591 91 84-99
Year of birth
Location of farm
exnosed cases in stratum
Person-years Crude Adjusted
0 4 years
Orchards or greenhouses
Horticulture and pesticide pur-
Orchards or greenhouses and pes-
Orchards or greenhouses
251,042 1.44 1.38
3,802,182 1.01 0.98
1,117,300 1.18 1.11
151,068 1.19 1.19
54,293 1.55 1.55
1.771.374 1.04 1.08
'Sub'ects born 1952-1964 followed up from 1971; subjects born in 1965-1991 followed up from
birth.-JAdjusted for year of birth and calendar ~ear.-~Restricted to subjects covered in the 1969
census (total n = 243,659; 4,280,456 person-years).QReference: subjects from holdings with no
horticulture or pesticide p~rchase.-~Reference: subjects from holdings with no orchards, green-
houses, or pesticide purchase.
pesticide purchase (RR, 2.11; 95% CI, 1.19-3.75) were indepen-
dent risk factors. The independent effect of chicken farming
was more moderate (RR, 1.77; 95% CI, 0.99-3.17).
The rates for non-astrocytic neuroepithelial tumours were
high in all age groups for those exposed to pig farming or
pesticide purchase. The association with pig farming was
evenly distributed in all age groups, whereas the association
with pesticide purchase was strongest for children under 15
years of age. For pesticide purchase, offspring aged 0 to 14
years had 41 brain tumour cases (adjusted RR, 1.71; 95% CI,
1.11-2.63) and 22 cases of non-astrocytic neuroepithelial
tumours (adjusted RR, 3.37; 95% CI, 1.63-6.94). Pesticide
purchase was positively associated with non-astrocytic tumours
in all categories of period of follow-up and year of birth.
However, the association was slightly stronger for children
born between 1980 and 1991, and during follow-up 1985-1991
(data not shown).
The risk increase for non-astrocytic neuroepithelial tumours
in association with pesticide purchase was not restricted to
specific types of farming, but particularly high incidence was
KKI\1 bNSFN I I I [
I ABLE V - RR FOR BRAIN TUMOURS, 1965-1Q91‘ FOR EXPOSURE INDICATORS LINKED TO ANIMAL
HUSBANDRY AND PESTICIDE USE IN OFFSPRING BORN 1952-1991 (n = 323,292) TO PARENTS IN
AORICULTIJRAL WORK ACCORDING TO THE NORWEGIAN AGRICULTURAL CEYSUSES 1969-19S9
informe t ion2
Person-years Crude Adjusted
Pig farming Non-astro-
cytic new Chicken
1,117,300 2 10
1.29 0.95-1.77 49 1.28
1.54 0.89-2.65 17
‘Sub ects born 1952-1964 followed up from 1971; Subjects born 1Y65-1991 followed up from
birth.- J See “Material and Methods” for definition; adjusted for year of birth and calendar
census (n = 243,659; 4,280,456 person-years).- Y GIioma not otherwise specified, choroid plexus
ycar.-?Adjusted for year of birth and calendar ~ar.-~Restricted to subjects covered in the 1969
papilloma, ependymoma, oligodendroglioma, rnedulloblastoma, ganglioglioma, and neuroblas-
found among offspring aged 0 to 4 years on farms with pesticide
purchase and grain farming combined (6 exposed cases; 3.8 per
100,000 pcrson-years; RR, 8.01; 95%) CI, 1.62-39.7).
The associations with pig farming and chicken farming, and
pesticide indicators were also investigated for medulloblas-
toma which was classified in the non-astrocytic neuroepithelial
group. Eight out of a total of 15 mcdulloblastoma cascs were
exposed to pigs, and the adjusted RR was even higher than for
the wholc non-astrocytic neurocpithelial group (RR, 4.92;
95%) CI, 1.72-14.1). Chicken farming was also strongly associ-
ated with medulloblastoma (7 exposed cases; adjusted RR,
3.91; 95% CI, 1.45-10.5). For pesticide purchase, the RR estimate
was doubled, ie., weaker than for the total non-astrocytic group.
Tablc V also includcs RK estirnatcs for thc sub-set of
offspring with relevant information lrom the index census.
Compared with the total cohort, the estimates for non-
astrocytic neuroepithelial tumours were slightly increased in
association with both pig farming and pcsticidc purchasc; the
estimate for association with pesticide purchase was increased
in this sub-set even for the age group 0 to 14 years (RR, 4.02;
95% CI, 1.78-9.08).
Offspring of a parent who worked at least 500 hr annually on
the farm also showcd stronger associations than the total
cohort bctwcen non-astrocytic ncurocpithelial tumours and
exposure to pig farming (RR, 3.YY; Y5% C1, 2.06-7.73) or
pesticide purchase (RR, 4.76; 95% CI, 1.92-11.8).
Thc distribution of month of birth among offspring with
brain tumours in association with pcsticide purchasc was also
investigated. Among children aged 0 to 14 years, with the
pesticide purchase indicator, 50% of the non-astrocytic neuro-
epithelial tumours (11 out of 22) and astrocytomas (6 out of
12) were born between April and June. Using children without
the pesticide purchase indicator as reference, the RR estimate
of non-astrocytic tumours for cxposcd childrcn born bctwecn
April and June w;js 6.15 (95% C1, 2.66-14.2) and only 2.30
(95% C1, 1.00-5.30) for exposed children born between July
The RR cslimatcs lor an association betwccn indicators of
exposure to pesticides as well as contact with animals on the
one hand and acute lymphocytic or myelocytic leukaemia on
the other were close to unity (Table VI). For acute leukaemias
there was no trend in the rates for increasing pesticide
expenditure (test for trend, p = 0.37). An increased RR of
bordcrline significance was Ibund for other acute leukaemias
in association with animal husbandry; the RR was close to
unity for pesticide purchase. The RR for other acute leukae-
mias were increased in association with all animals species, but
were unexpectedly strongest for pig farming. Chicken farming
and dairy farming were associated only moderately with other
acute leukaemias. For most exposures to animals, analyses of
the “relevant” information sub-group produced lower RR
cstimates, except for pig farming. Analyscs for the sub-group
of offspring to a parent who workcd more than 500 hr annually
on the holding also produced point estimates closer to unity
(for pig farming, RR, 1.78; 95% CI, 0.83-3.81).
Other associatioris in a priori hypotheses
There was no association between testicular cancer and
exposure to pesticides (Table VII) or the level of pesticide
expenditurc (test for trend, p = 0.40). An increased risk was
found for Hndgkin’s disease in association with lbrcstry, but
after adjustment for year of birth and calendar year the
estimate was not significant. The associations between grain
farming and soft-tissue sarcomas or lymphomas were all close
to unity. The RR for non-Hodgkin’s lymphoma in association
with pesticide purchase was 1.67, with a dose-response relation-
ship for different levels of expenditure (test for trend,p = 0.04).
This association was largely restricted to horticulture, if
pcsticide purchase was reported. Analysis restricted to the
sub-sct with “relevant” inlormation yielded an evcn higher risk
estimate for the latter association (10 exposed cases; adjusted
CANCFR IN OFFSPRING OF FARMERS
__ ~ _ _
1,117,300 1 .64
0.9 5-5.5 1
'Sub'ects born 1952-1964 followed up from 1971; subjects born 1965-1991 followed up from
birth.- 1 Adjusted for year of birth and calendar year.-%ee "Material and Methods" for definition,
adjusted for year of birth and calendar year.tRestricted to subjects covered in the 1969 census
243,659; 4,280,456 person-years).
BRAIS TL'MOUKS ASD LLLKAEMIAS). ANT) EXPOSC'RE INDICATOKS IN OFFSPRING BORN IK 1952-1991
Ir = 323.?Wr 1'0 PAREUIS IN A(;RICULTURAL WORKA('C0KDING TO 1HE NOKW€GIAS A(IRICU1TURAL
CENSUSES IK 1969-1989 RESULTS OF POISSON REGRESSION ANALYSIS
. I PK'KIORI SUSPtCTFI) ASSOCIATIO\S UFTWEES CAN( ER DIAGNOSED IN I W i 1031, (LXCLI'I
e k w d cases
Person-years Crude Adjusted
Testicular cancer Pesticide purchase3
Soft-tissue sarcoma Grain farming
Horticulture and pes-
'Sub'ects born 1952-1964 followed up from 1971; subjects born 1965-1991 followed up from
birtdAdjusted for year of birth and calendar ~ear.-~Restricted to males covered in the 1969
census (n = 125,571; 2,202,325 per~on-years).-~Restricted to subjects covered in the 1969, 1979 or
1989 censuses (n = 322,270; 5,678,035 per~on-years).-~Restricted to subjects covered in the 1979
census (n = 300,555; 5,292,372 person-years).-6Restricted to subjects covered in the 1969 census
(n = 243,659; 4,280,456 persori-years).
Associations not included in the a priori hypotheses
The associations between horticulture or exposure to pesti-
tides and cancer at an early age, and bet~~een
and cancer at later ages were also reflected in other specific
groups of neoplasms (Table VIII).
Some of the associations between indicators of pesticide use
in horticulture and the comnioncr malignancies in infancy
were strong. Although there were few exposed cases, signifi-
cantly increased RR were found between exposure to orchards
or greenhouses and Wilms' tumour, especially when use of
pesticide spraying equipment was reported. Field vegetable
TABLE VIII - POSITIVE ASSOCIATIONS NOT SUSPECTED A PRIORI BETWEEN CANCER AND EXPOSURE INDICATORS FOR OFFSPRING BORN 1952-1991
(n = 323,292) TO PARENTS IN AGRICULTURAL WORK ACCORDING TO THE NORWEGIAN AGRICULTURAL CENSUSES 1969-1989:
RESULTS OF POISSON REGRESSION ANALYSIS
(age 0-4 years)
mixed cellular tvue
‘See “Material and Methods” for definition, adjusted for year of birth and calendar year.-2Adjusted for year of birth and calendar
~ear.-~Restricted to subjects covered in the 1969 census (n = 243,659; 4,280,456 per~on-years).-~Restricted to subjects covered in the
1979 census (n = 300,555; 5,292,372 person-years).-SReference: subjects from holdings with no orchards, greenhouses, or pesticide
purchase.-6Reference: subjects from holdings with no field vegetables or pesticide purchase.
Person-years Crude Adjusted
in stratum RR
Orchards or greenhouses
Pesticide spraying equipment4
Orchards or greenhouses and pesticide
Field vegetables and pesticide p~rchase~.~ 4
farming was a risk factor both for eye cancer and for neuroblas-
toma at young age. However, only 2 of the 4 exposed
eye-cancer cases were retinoblastomas.
A positive association was found between chicken farming
and osteosarcoma, whereas an increased RR of borderline
significance was seen for Hodgkin’s disease; the latter associa-
tion was confined to the mixed cellular type (Table VIII).
The associations reported in Table VIII were stronger when
the analyses were restricted to the sub-set of children with
“relevant” information from the index census. The exception
was the association between chicken farming and osteosar-
coma, but the slightly decreased RR was still significant.
Analysis of the association for the sub-set of the cohort with a
parent who worked at least 500 hr annually on the farm yielded
a RR of 4.15 (95% CI, 1.61-10.7).
The total cancer experience among the offspring of farm
holders was similar to that of the rural population of Norway,
in accordance with case-control (Hemminki et al., 1985; Olsen
et al., 1991) and proportionate mortality (Sanders et al., 1981)
studies in other countries. The incidence of cancer at specific
sites did not deviate significantly from reference values in the
whole study population. Offspring of a parent who worked 500
hr or more annually on a farm had moderate increases in the
SIR for testicular cancer, nervous-system tumours, Hodgkin’s
disease and bone cancer. However, the increase was significant
only for testicular cancer.
For cancer at all sites, male offspring had a SIR slightly
above unity, whereas the female SIR was below unity. This
difference can be explained only partially by low rates for
cancers of the breast and cervix and high rates of testicular
cancer. Since the difference encompasses several sites, chance
is a plausible explanation. The gender difference at the ages of
5 to 19 years could also be due to environmental factors that
act after birth. Children of farmers are unique in that they live
at their parents’ workplace and are potentially exposed to
occupational agents. Most fatal accidents among farmers’
children are linked to farm activities, and affect boys far more
often than girls, even in the 0 to 4 year age group (Directorate
of Labour Inspection, Oslo, personal communication). It is
therefore probable that the risk of accidental childhood
exposure is higher for boys than for girls.
The Poisson regression results indicate that pesticides poses
a risk for some of the commonest malignancies of infancy and
early childhood, whereas contact with animals, in particular
poultry and pigs, constitutes a risk for some of the malignan-
cies most typical of late childhood and adolescence.
The most interesting confirmation of an a priori hypothesis
was the clear relationship between brain tumours and indica-
tors of exposure to pesticides and contact with animals.
Children aged 0 to 14 years had a nearly doubled risk for brain
tumours and a more than tripled risk for neuroepithelial
tumours other than astrocytomas in association with pesticide
purchase on the farm; RRs also increased by increasing
expenditure levels. Even stronger associations were seen for
sub-groups of offspring considered to have grown up on the
farm or whose parents had a large work input on the farm,
strengthening the evidence for a true relationship. The results
are in accordance with those of several case-control studies in
which indicators of parental or childhood exposure to pesti-
cides or insecticides were associated with brain tumours
(Preston-Martin et al., 1982; Sinks, 1985; West, 1988; Wilkins
and Koutras, 1988; Davis et al., 1993; Bunin et al., 1994). In
those studies, the odds ratios were 1.5 to 2.0 and above,
although several of the results were nonsignificant because of
low exposure prevalence. Contrasting our results, West (1988)
found that pesticides were associated more closely with astro-
cytoma. Use of insecticides was also reported in all case homes
in a report of a cluster (Wilkins et al., 1991). No increased risks
were found, however, in other studies in which contact with
pesticides (Howe et al., 1989) or use of insecticides in the home
before diagnosis (McCredie et al., 1994u, b) were investigated.
In a study of gliomas in adults, several groups of pesticides
were found to be risk factors (Musicco et at., 1988).
The credibility of a true relationship between pesticides and
specific brain tumours in our study is strengthened by the
space-time pattern of nervous-system tumour incidence in the
cohort with an increasing SIR during the last years of fol-
low-up and in offspring born 1980 to 1991. The same strata had
a stronger association between pesticide purchase and non-
astrocytic neuroepithelial tumours. Also, the highest SIR was
found in the south region, where pesticides are more exten-
Clustering of neuroepithelial brain tumours in offspring
born April to June to parents reporting pesticide use may
indicate that paternal exposure 0 to 3 months before concep-
tion is crucial. Wilkins and Sinks (1990) found that the
association between glioma and having a father in farming was
strongest when he had held this occupation during the pre-
CANCER IN OFFSPRING OF FARMERS
conception period. West (1988) found that indicators of
paternal exposure to pesticides constituted a risk for several
histologic sub-types of brain tumours.
The association between pig farming and brain tumours was
clear. RR was significantly increased by more than 50 percent
for all brain tumours and 5-fold for medulloblastoma. Chicken
farming also was associated with medulloblastoma. Our results
are in accordance with Bunin et al. (1994), who reported
elevated odds ratios for the tumour category including medul-
loblastoma in association with pigs and poultry. Toxoplasma
gondii infection is a potential cause of brain tumours that is
worth considering, since it infects domestic animals including
chicken and pigs, and is even a suspected cause of glioma in
animals (Schuman et al., 1967). Pig farmers in Finland had an
increased prevalence of antibodies to this micro-organism
(Seuri and Koskela, 1992). In a case-control study of children
and adults with tumours of the central nervous system, a
significant association was found between antibodies to Toxo-
plasma and gliomas (Schuman et al., 1967). In another study, a
relationship was found with meningiomas but not with gliomas,
but the cases included only adults (Ryan et al., 1993).
The SIR analysis showed that leukaemia incidence was not
increased in the study population, and the Poisson regression
analysis did not indicate a relationship between animal hus-
bandry or exposure to pesticides and acute lymphocytic or
myelocytic leukaemia. The RR for other acute leukaemias
were increased in association with contact with several animal
species: the association was strongest for pig farming but was
of borderline significance. Similar results have been reported
for adult farmers (Blair et al., 1992). The evidence for a true
relationship is not convincing, however, since most of the
associations were weaker for the sub-set of the study popula-
tion for which presumably more relevant census information
was available and for offspring from holdings where a parent
worked at least 500 hr annually.
Interpretation of the results for leukaemia are difficult, since
classification of sub-types in the Cancer Registry changed
during the study period. Most of the lymphocytic and myelo-
cytic sub-types were diagnosed later than 1975, and several
other acute leukaemias would probably be classified as lympho-
cytic or myelocytic today. The hypothesis of an association
between exposure to pesticides and acute myelocytic leukae-
mia at a young age (Buckley et al., 1989; Buckley, 1992) is not
supported by our results.
Moreover, the suspected, association between soft-tissue
sarcoma and lymphoma and exposure to phenoxy acids in grain
farming and forestry (Blair et al., 1992) was not supported by
our data. An increased RR for Hodgkin’s disease was found
for offspring from farm holdings with forestry, but the adjusted
estimate was not significant. Our data suggest that parental use
of pesticides in horticulture is a risk factor for non-Hodgkin’s
lymphoma in childhood. The RR for pesticide purchase follow
a dose-response pattern. As the increase is largely restricted to
horticulture, a relationship is suggested with insecticides
rather than phenoxy herbicides, which are prevalent in grain
farming. Support for our result is provided by the results of
several studies of non-Hodgkin’s lymphoma in adults, in which
insecticides (Cantor, 1982; Woods et al., 1987; Zahm et al.,
1990,1993; Cantor et al., 1992) and orchard farming (Pearce et
al., 1985, 1987) constituted risk factors.
Testicular cancer was associated neither with the available
indicators of exposure to pesticides nor with horticulture,
where organochlorine pesticides with oestrogenic effects are
used. The theory that intra-uterine exposure to such pesticides
is a cause of testicular cancer (Sharpe and Skakkebzk, 1993) is
therefore not supported by our results. The increased SIR for
testicular cancer among farmers’ sons, especially at the ages of
15 to 19 years, is at variance with the only other report on
parental occupation and testicular cancer (Kardaun et al.,
1991). Our data suggest that testicular cancer is associated
with farm practices that were common in the western part of
Norway. Risk factors for testicular cancer other than exposure
to pesticides in the study population are reported elsewhere
(Kristensen et al,, 1995a).
Risks not included in the study hypotheses
Several positive associations not included in our study
hypotheses were found, although they should be interpreted
with caution, since many associations were investigated. The
credibility of several of the results is strengthened, however, as
they followed a specific pattern: tumours of infancy were
associated with indicators of exposure to pesticides and horti-
culture, and malignancies that are commoner in later child-
hood were associated with indicators of contact with animals.
Wilms’ tumour was related to living on a farm with orchards
or greenhouses and pesticide spraying equipment. A signifi-
cant 9-fold risk was found for offspring with both these
exposure indicators, but this was based on only 4 exposed
cases. This result is in agreement with those of a study from
Brazil (Sharpe et al., 1995), reporting paternal and maternal
pesticide exposure as strong risk factors. It is also in agreement
with results from the National Wilms’ Tumor Study in the US,
in which insecticide application during the last 3 years before
diagnosis constituted a significant risk factor (Olshan et al.,
1990, 1993). Parental farming or rural farming residence has
not been identified as risk factors of Wilms’ tumour, however
(Kantor et al., 1979; Wilkins and Sinks, 1984; Olshan et al.,
1990). A relationship between paternal farming and childhood
death from renal tumour has been reported (McDowall, 1985).
Growing field vegetables combined with pesticide purchase
constituted risk factors of borderline significance for eye
cancer and neuroblastoma. Eye cancer has been associated
with the rural environment (Doll, 1991), but neuroblastoma
has not been related to parental farming (Spitz and Johnson,
1985; Davis et al., 1987; Wilkins and Hudley, 1990), except in
one study (Bunin et al., 1990). Detailed exposures were not
assessed in those studies.
Chicken farming was associated with some of the common
cancers of later childhood. The strongest associations were
found for osteosarcoma and the mixed cellular type of
Hodgkin’s disease. To our knowledge, similar findings have not
been reported, except for a suggestion of an association
between Hodgkin’s disease at young age and contact with
rabbits (Dorken, 1975). It is interesting that chicken farming
was a stronger risk factor than farming of other animal species.
Chicken have been suspected of inducing malignancies in adult
farmers through poultry viruses or chronic antigenic stimuli
(Blair et al., 1992). Exposure to organic dust containing
micro-organisms may be very high in hen houses (Clark et al.,
The study has some design features that ensure its validity.
Use of the personal identification number made possible
complete identification, linkage and follow-up, and cancer
registration in the Cancer Registry of Norway is considered to
be complete. Failure of inclusion of children born before 1965
who died before the 1970 population census would introduce a
selective loss and a negative bias if a large proportion died of
cancer. This bias was avoided by starting follow-up after the
1970 population census for children born between 1952 and
Agriculture in Norway occurs mainly on small and medium-
sized farms that are owned and operated by the family. Only
10% of the total agricultural workforce in the 1970 population
census were employees (Central Bureau of Statistics, 1975),
who did not participate in the agricultural censuses. The
national agricultural and horticultural censuses therefore offer
an opportunity to identify most people engaged in agricultural
work. We did not include offspring of farm owners born before
1925. On the basis of the age distribution of farm owners and
the fertility of Norwegian farmers, we estimated that about
15% of all farmers’ offspring born between 1952 and 1991 were
children of farm owners born before 1925.
Inclusion criteria in the agricultural censuses were loose,
and a large proportion of the parents had a low agricultural
work input. The inclusion of subjects with a peripheral connection
to farming may constitute a problem in the interpretation of the
results of both the SIR and the Poisson regression analyses. We
therefore performed separate analyses confined to offspring of
farmers defined according to the standard occupational code.
Cohort subjects could also have parents who were not
farmers at the time of conception or birth, since the cohort was
based on information obtained at the agricultural censuses,
1969-1989, whereas the offspring under study were born
between 1952 and 1991. We were unable to quantify offspring
born before the first census participation, whose parents
started in farming after the birth of the child. However, this
problem is not likely to be substantial: less than one thousand
new farms were settled in the 1950s and even fewer in the
1960s. During the same period, farms were almost entirely
taken over by children (mainly sons) who lived on the farm.
The main structural change in Norwegian agriculture during
the study period has been a downward trend in the number of
holdings and the number of people engaged in agricultural
production. Therefore, farm owners whose children were born
after the census year could have left the farm at the time the
child was conceived or born. However, the inclusion of
offspring of former farmers into the cohort would not be a
major problem: less than 10,000 offspring, including only 8
cancer cases, were born after the last census participation of
the parents (the majority in 1990-1991).
The main problem of our study was the use of crude proxies
for true exposures and resulting exposure misclassification in
the Poisson regression analysis. This may be most relevant for
pesticides, as we had only information on money spent on
pesticides or spraying equipment. We have assumed that
associations with these indicators and with grain farming and
forestry reflect exposures to phenoxy herbicides, and that the
indicators of exposure to pesticides and work in orchards and
greenhouses are related to exposure to organochlorine, organo-
phosphate, and carbamate compounds. Although the ap-
proval, uses and application of pesticides were firmly regulated
in the study period, our assumptions can be questioned, and
inferences about types of pesticides used can hardly be made
on the basis of our data. Several potential exposures to animals
on individual farms are also unknown, such as the presence of
zoonotic viruses or antigenic provocation by protein dust.
Equally problematic is the cross-sectional nature of our
information on exposure. We have to assume that activity on a
farm during the index census year reflects the activity before
conception, during pregnancy or in infancy. This assumption
introduces misclassification, which is most serious for cancer
occurring after the first years of life, to which subjects born
before the first census in 1969 make a considerable contribu-
tion. The problem affects in particular information unavailable
at all censuses, such as that on pesticide use; pesticide
purchase information was available at the 1969 census, but the
association with brain tumours was strongest for children born
10 to 20 years later. The cross-sectional information on
exposure offers little or no opportunity to make inferences
about the potential mechanisms of tumourogenesis, except for
the birth-month clustering of cases associated with pesticide
purchase, which may be compatible with a paternal-mediated
mechanism of pesticides.
The limitations of the quality of the information on exposure
and its timing are not, however, related differently to the
outcomes under study. The result of such non-differential
misclassification for dichotomous categories will be a bias
towards unity for any true association. We should therefore
regard the results for the unconfirmed hypotheses as “non-
positive” rather than negative.
Also the SIR estimates could be biased towards unity. This
could be due to inclusion of offspring whose parents were not
living or working on the farm at the time of conception or birth.
Also, 89% of the study population lived on farms in rural
municipalities, and contributed to the person-time experience
of the total rural population. The study cohort had a person-
time experience that was 0.20 to 0.25 that of the total rural
population from 1965 to 1991 for people under 20 years. This
ratio declined rapidly to 0.11 for ages 25 to 29 years and 0.01
for ages 35 to 39 years. The contribution of the study
population to both the numerator and the denominator will
lead to SIR estimates biased towards the null value, although
the impact of this bias is limited for SIR close to unity. If the study
population’s person-time experience is subtracted from that of the
reference population, providing a “worst-case” scenario, none of
the reported SIR would change by more than a few percent.
Our results could be influenced by potential confounders.
We had no information on tobacco smoking and alcohol
consumption among the parents, but the cancer profile among
the adult farmers strongly indicates low prevalences of both
smoking and alcohol consumption compared with the total
rural population (Kristensen et al., 199%). If parental smoking
and alcohol consumption were risk factors, confounding could
be the consequence, especially for the SIR results. However,
parental lifestyle factors are not firmly established as risk
factors for cancer in their offspring. Also, the selection of
younger parents (born after 1924) could introduce confound-
ing with regard to cancers related to parental age or parity;
however, stratification on parental age in the analyses did not
influence point estimates.
Although our study lacks precise exposure characterization,
several results are in agreement with other reports, and
farmers should consider, when handling pesticides, that even
their offspring could be at risk of cancer. Further studies
should address specific groups of pesticides and potential
mechanisms for cancer development caused by animal contact.
Dr. T. Bjerkedal, Dr. P. Laake and Dr. T. Norseth have
offered valuable supervision and advice at all stages of the
study. We thank Mr. S. Hansen and Mr. A. Johansen for file
linking and preparation in the Cancer Registry, Mr. 0.
Sandvin for designing reference rate files, and Dr. E. Heseltine
for revision of the manuscript. This work was supported by the
Research Council of Norway (grant 103542/110).
BLAIR, A., ZAHM,
J.F. JR., Clues to cancer etiology from studies of farmers. Scand. J.
Work Environ. Health, 18, 209-215 (1992).
S.H., PEARCE, N.E., HEINEMAN,
E.F. and FRAUMENI,
register-based analysis. Report 86/27. Central Bureau of Statistics of
Norway, Oslo-Kongsvinger (1986).
H. and KRAVDAL, 8.,
Fertility by birth order in Norway: a
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