International Journal of Epidemiology Vol. 25, No.

6
© International Epidemiological Association 1996 Printed in Great Britain

Cancer Incidence among Icelandic

Pesticide Users
YUNA Z H O N G * " AND VILHJALMUR RAFNSSON***

Zhong Y (Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing, People's Republic of
China) and Rafnsson V. Cancer incidence among Icelandic pesticide users. International Journal of Epidemiology 1996;
25: 1117-1124.
Background. This study was done to examine the cancer risk among pesticide users in Iceland.
Methods. We have followed a cohort of 2449 licensed pesticide users, students from a horticultural college, members
of a pension fund for market gardeners, horticulturists and vegetable farmers up until the end of 1993 in the Icelandic
Cancer Registry of cancer incidence. The observed number of cancers was compared with expected values calculated
on the basis of cancer incidence for males and females in Iceland.
Results. The standardized incidence ratio (SIR) for all cancer sites was 0.80. Among females the increased incidence
for cancer of lymphatic and haematopoietic tissue was significant (SI R = 5.56, 95% confidence interval (Cl) 1.12-16.23).
The incidence of rectal cancer was three times that expected (SIR = 2.94, 95% Cl : 1.07-6.40), and this cancer was even
more predominant among the licensed pesticide users (SIR = 4.63, 95% Cl : 1.49-10.80). All cancers of the rectum were
adenocarcinoma, however, one was adenocarcinoma in villous adenoma and one adenocarcinoma in tubulo-villous
adenoma.
Conclusion. The results provide some support for the suggestion that pesticide exposure may lead to cancer of the
lymphatic and haematopoietic tissue in females. We suggest that some of the pesticides to which the licensed pesticide
users were exposed may lead to rectal cancer.
Keywords: cancer registry, pesticide, phenoxy acetic acids, rectal cancer, adenoma, adenocarcinoma

The possible long-term health effects related to pesti-
cides and herbicides, in particular their carcinogenic
effects, have been studied for several years, and several
reviews have appeared recently.1"4
In the cohort approach attempts have been made to
follow pesticide manufacturers, licensed pesticide
applicators or users, and farmers, and the assumed ex-
posure has been described, defined, or measured using
different procedures.1"4 When using historical cohorts
exposure estimates have often been the main weakness
of the studies. In addition some of the neoplasms re-
lated to exposure to pesticides and herbicides are rare
and lymphatic and haematopoietic cancers might be
underreported on death certificates.
The studies where cancer incidence has been used
as an endpoint among manufacturers have shown an
increased risk of soft tissue sarcoma,5'6 non-Hodgkin's
* Institute of Occupational Medicine, Chinese Academy of Preventive
Medicine, Beijing, People's Republic of China.
*• Department of Occupational Medicine, Administration of
Occupational Safety and Health, Reykjavik, Iceland.
' Department of Preventive Medicine, University of Iceland,
Reykjavik, Iceland.
Reprint requests: Vilhjdlmur Rafnsson, Department of Occupational
Medicine, Administration of Occupational Safety and Health, PO Box
12220, 132 Reykjavik, Iceland.
1117
lymphomas 5 ' 6 and lung cancer. 5 During the first
follow-up period excesses observed for rectal cancer in
males and cervical cancer in females were thought to be
possibly due to chance.5
Other studies of cancer incidence, done on pesticide
applicators in Sweden, have shown deficits of cancers
of the lung, liver, pancreas, kidney and prostate, and
non-significant excesses for non-Hodgkin's lymphoma
and Hodgkin's disease and an excess of cancer of the
testis 10 or more years after they became licensed pesti-
cide applicators.7'8 In a small mortality and morbidity
study of Finnish chlorophenoxy herbicide applicators
over an 18-year period the results did not suggest that
the exposure carried any significant risk of cancer.9 In
a study on gardeners which were followed through the
Danish Cancer Registry excesses were found for soft
tissue sarcoma, non-Hodgkin's lymphoma and chronic
lymphatic leukaemia.10
A cancer incidence study on census registered
farmers in Sweden showed deficits of cancer of the
tongue, throat, liver, larynx and lung, and lower than
average risks of cancer of the oesophagus, duodenum
and small intestine, colon, biliary passage, cervix uteri,
kidney, urinary organ and endocrine glands,11"13 how-
ever, a significant excess was found for lip cancer."
Further studies on the same cohort showed increased

Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427

by guest
on 24 February 2018
 1118 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

TABLE 1 Number of people in the different subgroups and the TABLE 2 Amount (kg of active chemical) of pesticide sold for
year the first person entered the study agricultural purposes during the years 1976-1993 (except 1989)
in Iceland according to information from the Committee on Toxic
Substances
Groups Year of entry Males Females Total
to study
Chemical name

Subgroup I 1973 716 108 824

Subgroup II 1941 328 174 502 (2,4-dichlorophenoxy) acetic acid 2252
Subgroup III 1970 1071 447 1518 Parathion 1430
Subgroup IV 1967 59 5 64 Lindan 1427
Subgroup V 1982 138 15 153 Chlorfenvinphos 1092
Subgroup VI 1985 158 21 179 Chlormequachlorid 986
Isofenphos 689
Diazinon 634
Malathion 539
Fenithrothion 513
risk of multiple myeloma,14 and in a subcohort an Diqual-paraquat-dichlor 414
increased risk was found for Hodgkin's disease,15 but Captan 313
there was a deficit of soft tissue sarcoma.16 In an incid- Dazomet 250
Dichlororvos 248
ence study of Icelandic farmers a deficit was found 238
Probamocarb
for all cancers, cancer of the colon, lung, prostate, and Diquat-dibromid 238
urinary organs, and a non-significant excess of lip can- Primicarb 195
cer, non-Hodgkin's lymphoma, Hodgkin's disease and Metaldehyd 133
130
leukaemia. 17 Dimethoat
128
Benomyl
The aim of our study was to evaluate the cancer risk Aldicarb 119
involved in pesticide use in Iceland. (2,4,5-trichlorophenoxy) acetic acid 114

MATERIAL AND METHODS

Cohort
The total cohort comprised 2449 people, 1860 (76%)
men and 589 (24%) women. The cohort consisted of six
subgroups (Table 1), which had encountered pesticides
in different ways. There was some overlap between the
groups so in the analysis of the total cohort there are
somewhat fewer people than if the subgroups had been
simply added together. Every resident of Iceland has
a personal identification number which he or she uses
throughout life, and all subjects in the cohort were
registered using this number.
Subgroup I consisted of special licensed individuals
who were allowed to buy and handle different toxic
materials including pesticides. Included in this group,
which we consider to have had the heaviest exposure,
we were able to recognize those who had worked with
pesticides in the agricultural sphere, a total of 594
people. For this group information was available on the
year they were licensed, the year the licence expired
and what categories of pesticide they were allowed to
use according to a special classification issued by the
Committee on Toxic Substances.18 No information as
to the magnitude or mode of individual exposure was
available for these pesticide users. However, Table 2
shows a summary of different pesticides used for
agricultural purposes in Iceland according to available
annual sale lists from the Committee on Toxic Sub-
stances from 1976 to 1993, with the exception of 1989,
which was missing from the National Archives. The
licensed pesticide users underwent 2 days of training
under the auspices of the Committee on Toxic Sub-
stances when they were instructed in the use of pesti-
cides and other dangerous chemicals.
An attempt was made to classify pesticide users in
agriculture according to the type of activity in which
they were engaged. Two advisors on pesticide ap-
plication from the Farmers' Association of Iceland
were given a list with names of the pesticide users and
asked to arrange them in groups according to their main
activity. The same was requested of three chairmen of
local vegetable farmers' societies. In this way it was
possible to assign 339 pesticide users to six categories:
decorative flowers in greenhouses, vegetables in green-
houses (tomatoes, cucumbers, sweet peppers etc.),
vegetables outdoors (potatoes, rutabagas, cabbages
etc.), flowers outdoors, gardening and others.
Subgroup II was derived from the students' register
of the Icelandic Horticultural College. The training at
the College included courses on the use of pesticides.
The register records the year the students finished their
course but no information was available on their work
tasks or exposure from that time. It was possible to

Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427

by guest
on 24 February 2018
 CANCER IN ICELANDIC PESTICIDE USERS
identify all but two of the students by date of birth and
identification number.
Subgroup III was obtained from the register of the
Pension Fund of the Icelandic Market Gardeners'
Association. In this register there was information on
the year the members joined and the number of years
they had worked. On the other hand there was no
information on the individual work tasks or possible
exposure during the working period.
Subgroup IV contains members of the Horticultur-
ists' Association with information on the year they
became recognized as gardeners by the authorities after
some years of vocational training. For one person the
correct identification number was missing and he was
omitted from the study.
Subgroup V was obtained from the membership list
of the Association of Vegetable Farmers but only lim-
ited information was available as to how long they had
been active farmers.
Subgroup VI included people who were on a list of
vegetable producers obtained from the Farmers' Asso-
ciation of Iceland. It was not known how long they had
been engaged in vegetable production; however,
follow-up of this group started the first year they were
mentioned on the list.
Most information was available for subgroup I and
particularly for the licensed pesticide users who had
worked with pesticides in the agricultural sphere.
According to advisors from the Farmer's Association
these individuals were considered to have suffered the
most intense exposure, and in particular they had been
exposed to phenoxy acetic acids. The other groups
(subgroups II-VI) were, according to the advisors,
considered to have had low exposure and were included
in the study in order to contribute results on these low
exposure groups.9
Follow-Up
The cohort was followed up in the Icelandic Cancer
Registry from the date individuals became licensed
pesticide users (subgroup I), from the year they finished
horticultural school (subgroup II), from the first year
they were mentioned on the list of the pension fund
(subgroup III), from the first year in which they ap-
peared on the horticulturists' and farmers' lists (sub-
group IV-VI), or from 1955 if the person had entered
the group before that year. Follow-up went on until
1 December 1993 or until the death of the individual if
before that date. Through the personal identification
numbers, record linkage was established with the Ice-
landic Cancer Registry, the National Registry and the
Register of Deaths, after permission was obtained from
the Data Inspection Committee. In this way the vital
Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427
by guest
on 24 February 2018
1119
status of the study population was ascertained for all the
subjects. The Icelandic Cancer Registry was established
in 1955 and is a nationwide register of cancer cases,
more than 92% of which are histologically verified; the
register uses the seventh revision of the International
Classification of Diseases (ICD-7).19
Statistical Analysis
Person-years were calculated for each individual,
commencing with the first year in the study and ending
with his or her date of death or at the end of 1993. 20 ' 21
The number of expected cancers was calculated on the
basis of the sum of person-years for each 5-year age cat-
egory during the respective calendar years of the study
period, multiplied by the cause- and calendar-year-
specific incidence rate for Icelandic men and women
provided by the Icelandic Cancer Registry.
The ratio between observed and expected numbers of
cancers was calculated, i.e. the standardized incidence
ratio (SIR) along with a 95% confidence interval (95%
CI) assuming Poisson distribution by making use of
Byar's approximation.22
Subgroup I was restricted to those who had been licens-
ed to use pesticides in agriculture and was divided into even
smaller groups according to the main crop being grown.
In a case-referent approach cases of certain histo-
logical types of cancer were compared to all other
histological types of the same site registered in the
Icelandic Cancer Registry according to exposure to
pesticides. As the expected values were less than 5% in
some cells Fisher's exact test was used to calculate 95%
CI of the odds ratios (OR) and P-values.23
RESULTS
Table 3 shows observed and expected numbers for all
cancers and the different cancer sites for males and
females in the total cohort. Locations with only one or
no observed cases are combined with other sites. There
was a deficit of all malignancies and among males this
was mainly due to deficits of cancer of the stomach,
lung and prostate. There was an excess of cancer of the
rectum and lymphatic and haematopoietic tissue.
Table 4 shows observed and expected numbers for all
cancers and some cancer sites among the males and
females combined in the total cohort. The SIR was
high for cancer of rectum and other skin cancers.
The different subgroups where thus analysed separ-
ately. When this was restricted to those males and
females who were licensed to use pesticides in agri-
culture (part of subgroup I) the results for all cancers
and some cancer sites are as shown in Table 5. The SIR
for cancer of the rectum was high in this analysis (4.63).
 1120 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

TABLE 3 Observed (Obs.) and expected values (Exp.) for all cancers and different cancer sites, standardized incidence ratio (SIR) and
95% confidence interval (Cl) among males and females in the total cohort

Cancer sites (ICD-7) Obs. Exp. SIR 95% Cl

Men (21 547 person-years):

Oesophagus(150) 3 1.29 2.33 0.47-6.79
Stomach (151) 4 6.96 0.57 0.15-1.47
Small intestine (152) 2 0.37 5.41 0.61-19.52
Colon (153) 3 4.83 0.62 0.12-1.81
Rectum (154) 5 1.83 2.73 0.88-6.38
Pancreas (157) 4 2.34 1.71 0.46-4.38
Lung (162) 5 9.64 0.52 0.17-1.21
Prostate (177) 10 14.31 0.70 0.33-1.29
Testis(178) 2 1.67 1.20 0.13^».32
Other urinary organs (181) 3 5.81 0.52 0.10-1.51
Melanoma of skin (190) 1 0.87 1.15 0.02-6.40
Other skin (191) 5 1.77 2.82 0.91-6.59
Thyroid gland (194) 2 1.55 1.29 0.14-4.66
Lymphatic and hematopoietic tissue (200-204) 4 5.03 0.80 0.21-2.04
Non-Hodgkin's lymphoma (200,202) 2 1.83 1.09 0.12-3.95
Leukaemia (204) 2 1.58 1.27 0.14^1.57
Other sites 7 15.01 0.47* 0.19-0.96
All cancers (140-205) 59 72.41 0.81 0.62-1.05
Women (5194 person-years):
Stomach (151) 2 0.4 5.00 0.56-18.05
Lung(162) 2 1.01 1.98 0.22-7.15
Lymphatic and haematopoietic tissue (200-204) 3 0.54 5.56* 1.12-16.23
Non-Hodgkin's lymphoma (200,202) 1 0.18 5.56 0.07-30.91
Multiple myeloma (203) 1 0.09 11.11 0.15-61.82
Leukaemia (204) 1 0.16 6.25 0.08-34.77
Other sites 8 14.44 0.55 0.24-1.09
All cancers (140-205) 12 16.39 0.73 0.38-1.28

* P < 0.05; two-tailed.

TABLE 4 Observed number and expected values for all cancers and certain cancer sites among male and female combined in the total
cohort

Cancer sites (ICD-7) Obs. Exp. SIR 95% Cl

Rectum (154) 6 2.04 2.94* 1.07-6.40

Other skin (191) 5 1.91 2.62 0.84-6.11
Non-Hodgkin's lymphoma (200,202) 3 2.01 1.49 0.30-4.36
Multiple myeloma (203) 1 1.04 0.96 0.01-5.35
Leukemia (204) 3 1.74 1.72 0.35-5.04
Lymphatic and hematopoietic tissue (200-204) 7 5.57 1.26 0.50-2.59
All cancers (140-205) 71 88.80 0.80 0.62-1.01

* P < 0.05; two-tailed.

Looking at the licensed pesticide users according to
type of agricultural crop, did not uncover any indication
of an increased cancer incidence.
Analysis of cancer incidence in each of the other
subgroups (II-VI) did not reveal any increased cancer
risk and the number of cancer cases were few in each
group, the SIR yielding wide Cl. Cancer incidence ac-
cording to duration of exposure, measured as number of
years licensed as pesticide users (subgroup I), number
of years as market gardeners (subgroup III), did not
uncover any evidence of increased cancer incidence in
these subgroups.

Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427

by guest
on 24 February 2018
 CANCER IN ICELANDIC PESTICIDE USERS 1121

TABLE 5 Observed number, SIR, and 95% confidence interval among men and women who were licensed to use pesticides for agriculture
purposes

Cancer sites (ICD-7) Men Women Total

Obs. SIR 95% CI Obs. SIR 95% CI Obs. SIR 95% CI

Rectum (154) 4 3.92* 1.06-10.04 , 16.67 0.22-92.73 5 4.63* 1.49-10.80

Non-Hodgkin's lymphoma
(200,202) 1 1.09 0.01-6.05 0 - 0-73.36 1 1.02 0.01-5.68
Leukaemia (204) 0 _ O-^t.70 1 20.00 0.26-111.27 1 1.20 0.02-6.70
Lymphatic and haematopoietic
tissue (200-204) 1 0.41 0.01-2.30 1 6.67 0.09-37.09 2 0.78 0.09-2.80
All cancers
(140-205) 30 0.77 0.52-1.10 5 0.77 0.25-1.80 35 0.77 0.54-1.07

• P < 0.05, two-tailed.

TABLE 6 Cases of cancer of the rectum, age at diagnosis, duration of exposure, and histological number and histological diagnosis
according to information from the Icelandic Cancer Registry

Diagnosis Age (years) Sex Number of Duration of Histological Histological

(ICD-7) at diagnosis subgroup exposure (years) number diagnosis

ra
154 63 Female 12 82633 Adenocarcinoma in tubulo-villous adenoma
154 65 Male 8 81403 Adenocarcinoma
154 60 Male 5 82613 Adenocarcinoma in villous adenoma
154 71 Male 7 81403 Adenocarcinoma
154 78 Male 4 81403 Adenocarcinoma
154 65 Male IV b - 81403 Adenocarcinoma

" Subgroup I: licensed pesticide users.

b
Subgroup IV: members of the Gardeners' Association.

Information on the histological type of cancer of the
rectum was obtained from the Cancer Registry and
is shown in Table 6. All cancers of the rectum were
adenocarcinoma, but two were adenocarcinoma in
villous adenoma and tubulo-villous adenoma. Five of
these cases occurred in licensed pesticide users working
in the agricultural sector. These cases were discovered
by the record linkage of the licensed pesticide users
through the years 1973-1993. In order to evaluate the
importance of this finding a case-referent approach was
designed within the Cancer Registry. All cancers of the
rectum recorded in the registry during this period were
counted (398) as were the number of adenocarcinoma
in villous adenoma and adenocarcinoma in tubulo-
villous adenoma (15). The division into exposed and
unexposed was already known from the information on
licensed pesticide users. Table 7 shows the division of
cases and referents according to exposure. The OR was
19.49, 95% C I : 1.47-181.03. Thus there was a high risk
among the exposed of developing an adenocarcinoma in
villous or tubulo-villous adenoma.
As cancer of colon and rectum are considered aetio-
logically related, the histology of the four cases of colon
cancer was also scrutinized using the Cancer Registry.
The morphological diagnosis of all these cases were
adenocarcinoma (81 403) and two of them were li-
censed pesticide users. In a new case-referent approach
taking cancer of the rectum and colon together accord-
ing to the same histological type and whether exposed
as licensed pesticide user or not, the OR was 20.00,
95% C I : 1.82-127.35.
DISCUSSION
The deficit of all tumours among the total cohort and
the licensed pesticide users in this study is in agreement

Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427

by guest
on 24 February 2018
 1122 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY

TABLE 7 Cases of adenocarcinoma in villous adenoma compared to other rectal cancers according to exposure to pesticides defined as
those who were licensed pesticide users and active in the agricultural sphere

Exposure Diagnosis

Adenocarcinoma in All other malignant

adenoma (82 633,82 613) neoplasms of rectum

Licensed pesticide users active in agriculture 2 3

Not exposed 13 380

Odds ratio 19.49; 95% confidence interval 1.47-181.03; P-value 0.012, two-tailed.

with other studies of Swedish and Finnish pesticide
users. 7 ' 9 The people in the cohort were all profession-
ally active when they entered the study, which means
they are healthier than the total Icelandic population;
this introduces a potential bias due to the healthy
worker effect.
In the present study in which the pesticides exposed
cohort was divided into subgroups, besides looking for
the risk of soft tissue sarcoma, malignancy of the lym-
phatic and hematopoietic tissue'^1 and rectal cancer,5'24"28
and also analysing the cohort for the cancer risk at other
sites, concern about the need of adjustment for multiple
comparison may arise. There is no general agree-
ment on how to approach this phenomenon;29'30 some
maintain that no correction is needed for multiple
comparison,30'31 while others advocate the use of con-
fidence intervals rather than deciding merely from
P-values whether 'significant' or 'non-significant'
results have been obtained. 32 Nevertheless this calls
for different interpretation of the results for different
cancer sites. 22 ' 32
In this study there was only one case of soft tissue
sarcoma (code number 197 in ICD-7) versus 0.52
expected in the total cohort, which does not suggest any
special interpretation is needed.
We found seven cancers of the lymphatic and haem-
atopoietic tissue versus 5.57 expected in the total cohort,
and among females there were three cases versus 0.54
expected, which reaches statistical significance. When
those cases of lymphatic and haematopoietic tissue can-
cer were broken down into the different categories of
diagnosis or analysed in different subsets of the cohort
there was no indication of significantly increased can-
cer incidence. The smallness of the study is an obvious
drawback and limits its ability to detect an increased
risk for these rare cancers. This is possibly why we only
found excess cases of cancers of the lymphatic and
haematopoietic tissue among females.
The fourfold increased incidence of rectal cancer
among licensed pesticide users is consistent with results
from a cancer incidence study of Danish pesticide
manufacturers.5 Also, a significant excess risk of rectal
cancer was found in an Italian case-control study24 and
non-significant excesses were found in some other
studies.25"28 Still other studies have found a deficit of
rectal cancer among herbicide users.33'34 The results of
the analysis done with the case-referent approach
nested in the Cancer Registry showed that these find-
ings are interesting and warrant further studies to
evaluate the possible role of pesticide exposure in
development of rectal cancer.
The finding of an excess risk of skin cancer other
than melanoma is difficult to evaluate in the light of
former studies, as they do not differentiate between types
of skin cancer.5 A Swedish study of pesticide appli-
cators did show an increased incidence of skin cancer
other than melanoma7 and a possible relation between
skin cancer and exposure to pesticides has been
suggested in mortality studies.25'35 Other studies have
related such findings to exposure to solar radiation36
and this has been suggested in an overview of studies of
farmers.37
In the present study the total cohort was gathered
from various groups which were considered to be
exposed to pesticides in their professional careers. The
main attention was focused on the licensed pesticide
users because they were considered to have suffered
the highest exposure. The limitations of our study, i.e.
the lack of exposure measurements and acceptance of
certification as pesticide user as a surrogate for expos-
ure, have been discussed in former cancer incidence
studies 7 ' 9 as well as in mortality studies.24 Even though
a person becomes a licensed pesticide user, this gives
no indication of mode and magnitude of actual exposure.
The majority of pesticide users obtained their licenses
from 1973 onwards which is when the Committee on
Toxic Substances commenced issuing licenses; individ-
uals, however, might have been pesticide users for
several years before. This suggests a further underesti-
mate and uncertainty of exposure as estimated in terms

Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427

by guest
on 24 February 2018
 CANCER IN ICELANDIC PESTICIDE USERS
of licensed years. Attempts to get more information
from advisers and chairmen of the local farmers' soci-
eties to establish estimates of exposure failed as they
only had information on the production of the youngest
and still active pesticide users. The misclassification of
exposure should have led to underestimation of the true
incidence ratio.
The strengths of the study should also be mentioned.
First, the creation of the cohort is based on lists which
were made for administrative purposes. Even the re-
quirement of certification for pesticide users was based
on evaluation of the acute toxicity of the pesticides and
not their possible carcinogenicity. Thus the historical
development of the cohort was independent of the later
occurrence of cancer.
Second, a high proportion of the cancer cases re-
ported to the Cancer Registry are histologically verified
as previously mentioned.19 Cancer diagnosis is re-
corded and coded at the time of diagnosis by the staff
at the registry, under supervision of a pathologist, who
was unaware that the study would be undertaken later
and did not know whether cases were licensed pesticide
users.
Third, vital status could be ascertained for all cohort
members, thanks to record linkage through the National
Registry making use of identification numbers. The iden-
tification number is also used at the Cancer Registry
and no case of cancer is recorded or coded if the person
does not exist on the National Registry, thus securing
complete identification of cancer cases in the cohort.
Fourth, using the Cancer Registry provides an oppor-
tunity to study cancer sites which have not necessarily
resulted in death. This is an obvious advantage com-
pared to studies which use death as an endpoint with
regard to cancers such as those of the rectum or skin
and might explain why excess rectal cancer has not
been found more consistently in mortality studies of
pesticide exposure.
As none of the cases with rectal cancer were relatives
and there was no case of second cancer of the colon or
rectum, familiar factors and past history are unlikely
to be confounding the results on rectal cancer in the
present study. Dietary or lifestyle factors are not known
in detail for the licensed pesticide users, however, one
might assume that those active in the agricultural
sphere would have a lifestyle resembling that of other
farmers in Iceland. In the former cancer incidence study
of Icelandic farmers there was a deficit of many cancer
sites including cancer of the colon and rectum.17 In that
study it was suggested that something in their life-
style seemed to protect them from various types of
cancer. For this reason, maybe we should not in the
first instance look for confounding factors in lifestyle
Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427
by guest
on 24 February 2018
1123
parameters. Physical activity, both in occupation and
leisure, protect against colorectal cancer38 and it seems
unlikely that lack of physical activity is confounding
the findings on rectal cancer among the licensed
pesticide users in the agricultural sphere.
In conclusion, our study provides some support for
the suggestion that pesticide exposure leads to cancer
of the lymphatic and haematopoietic tissue among fe-
males. There was a deficit of all cancers including lung
cancer, but an excess of non-melanoma skin cancer.
The excess of rectal cancer lends support to a relation-
ship between exposure to pesticides and cancer of the
rectum. Scrutiny of the rectal cancer cases for their
histological diagnosis showed a high proportion of
adenocarcinoma in villous and tubulo-villous adenoma
which should provide the basis for further studies on
the pathogenesis of cancer of this location among those
exposed to pesticides.
ACKNOWLEDGEMENTS
This study has been supported by the Scientific Council
of the Icelandic Cancer Association. We wish to thank
the Environmental and Food Agency of Iceland, the
Icelandic Horticultural College, the Pension Fund of
the Market Gardeners' Association, the Horticulturists'
Association, the Association of Vegetable Farmers and
the Farmers' Association in Iceland for allowing us
access to their data. We also thank Kristin Bjarnad6ttir
and Hrafn Tulinius at the Icelandic Cancer Registry for
their assistance.
REFERENCES
1
Blair A, Zahm S H. Herbicides and cancer: a review and dis-
cussion of methodologic issues. In: Band P (ed.), Occupa-
tional Cancer Epidemiology. Berlin: Springer Verlag, 1990.
2
Maroni M, Fait A. Health effects in man from long-term ex-
posure to pesticides. A review of the 1975-1991 literature.
Toxicol 1993; 78: 1-180.
3
Morrison H I, Wilkins K, Semenciw R, Mao Yang, Wigle D.
Herbicides and cancer. Review. JNC1, 1992; 84: 1866-74.
4
McDuffie H H. Women at work: Agriculture and Pesticides.
J Occup Med 1994; 36: 1240-46.
5
Lynge E. A follow-up study of cancer incidence among workers
in manufacture of phenoxy herbicides in Denmark. Br J
Cancer 1985; 52: 259-70.
6
Lynge E. Cancer in phenoxy herbicide manufacturing workers
in Denmark, 1947-1987—an update. Cancer Causes and
Control 1993; 4: 261-72.
7
Wiklund K, Dich J, Holm L-E, Eklund G. Risk of cancer in
pesticide applicators in Swedish agriculture. Br J Ind Med
1989; 46: 809-14.
8
Wiklund K, Dich J, Holm L-E. Risk of malignant lymphoma in
Swedish pesticide appliers. Br J Cancer 1987; 56: 505-08.
9
Asp S, Riihimaki V, Hernberg S, Pukkala E. Mortality and
cancer morbidity of Finnish chlorophenoxy herbicide
 1124 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
applicators: An 18-year prospective follow-up. Am J Ind
Med 1994; 26: 243-53.
l0
Hansen E S, Hasle H, Lander F. A cohort study of cancer incid-
ence among Danish gardeners. Am J Ind Med 1992; 21:
651-60.
"Wiklund K. Swedish agricultural workers. A group with a
decreased risk of cancer. Cancer 1983; 51: 566-68.
12
Wiklund K, Steineck G. Cancer in respiratory organs of Swedish
farmers. Cancer, 1988; 61: 1055-58.
13
Wiklund K, Holm L-E. Trends in cancer risk among Swedish
agricultural workers. JNC1, 1986; 77: 657-64.
14
Steineck G, Wiklund K. Multiple myeloma in Swedish
agricultural workers. Int J Epidemiol 1986; IS: 321-25.
15
Wiklund K, Lindefors B-M, Holm L-E. Risk of malignant
lymphoma in Swedish agricultural and forestry workers.
BrJ indMed 1988; 45: 19-24.
16
Wiklund K, Holm L-E, Dich J. Soft tissue sarcoma risk among
agricultural and forestry workers in Sweden. Chemosphere
1987; 16: 2107-10.
17
Gunnarsdottir H, Rafnsson V. Cancer incidence among Icelandic
farmers 1977-1987. Scand J Soc Med 1991; 19: 170-73.
18
Log iim eiturefni og hattuleg efni. Nr 52/1988. Stj6rnartfdindi A
1988.
"Tulinius H, Ragnarsson J. Nygengi krabbameina d fslandi
1955-1984. (Cancer incidence in Iceland 1955-1984).
Heilbrig3isskyrslur, Fylgirit 1987, nr 3. Reykjavfk:
Icelandic Cancer Society and Director General of Health,
1987.
20
MacMahon B, Pugh T F. Epidemiology, Principle and Methods.
Boston: Little, Brown, 1970.
21
Axelson O. Epidemiologi for arbets-och miljb'medicin. (Epi-
demiology for occupational and environmental medicine.)
Lund: Studentlitterarture, 1981.
22
Breslow N E, Day N E. Statistical Methods in Cancer Research.
Volume II—The design and analysis of cohort studies.
Lyon: International Agency for Research on Cancer, 1987.
23
M e h t a C R, Patel N R, G r a y R. C o m p u t i n g a n e x a c t c o n f i d e n c e
interval f o r t h e c o m m o n o d d s ratio i n several 2 x 2
contingency tables. J Am Stat Assoc 1985; 78: 9 6 9 - 7 3 .
24
Forestiere F, Quercia A, Miceli M el al. Cancer among farmers
in central Italy. Scand J Work Environ Health 1993; 19:
382-89.
Downloaded from https://academic.oup.com/ije/article-abstract/25/6/1117/672427
by guest
on 24 February 2018
25
Swaen G M H, Van Vliet C, Slangen J J M, Sturmans F. Cancer
mortality among licensed herbicide applicators. Scand J
Work Environ Health 1992; 18: 2 0 1 - 0 4 .
26
Bond G G, Wetterstroem N H, Roush G J f l al. Cause specific
mortality among employees engaged in the manufacture,
formulation or packing of 2,4-dichlorophenoxyacetic acid
and related salts. Br J Ind Med 1988; 45: 98-105.
27
Saracci R, Kogevinas M, Bertazzi P A el al. Cancer mortality
in workers exposed to chlorophenoxy herbicides and
chlorophenols. Lancet 1991; 338: 1027-32.
28
Fingerhut M A, Halperin W E, Marlow D A el al. Cancer
mortality in workers exposed to 2,3,7,8-tetrachlordibenzo-
p-dioxin. N Engl J Med 1991; 324: 212-18.
29
Armitage P, Berry G. Statistical methods in medical research.
Oxford: Blackwell Scientific, 1991.
30
Rothman K J. Modern Epidemiology. Boston: Little, Brown, 1986.
31
Rothman K J. No adjustments are needed for multiple com-
parison. Epidemiol 1990; 1: 43^*6.
32
Hernberg S. Introduction to Occupational Epidemiology.
??Chelesea: Lewis Publishers, 1992.
33
Coggon D, Pannett B, Winter P D, Acheson E D, Bonsali J.
Mortality of workers exposed to 2 methyl-4 chloropheno-
xyacetic acid. Scand J Work Environ Health 1986; 12:
448-54.
34
Ott M G, Olson R A, Cook R R, Bond G G. Cohort mortality
study of chemical workers with potential exposure to the
higher chlorinated dioxin. J Occup Med 1987; 29: 422-29.
35
Wang J-D, Li W-E, Hu F-C, Hu K-H. Occupational risk and the
development of premalignant skin lesions among paraquat
manufactures. Br J Ind Med 1987; 44: 196-200.
36
Corrao G, Calleri M, Carle F, Russo R, Bosia S, Piccioni P.
Cancer risk in a cohort of licensed pesticide users. Scand J
Work Environ Health 1989; 15: 203-09.
37
Blair A, Hoar Zahm S. Cancer among farmers. In: Cordes D H,
Rea D F. Health hazards of farming. Occupational
Medicine: State of the art reviews 1991; 6: 335-54.
38
Potter J D, Slattery M L, Bostick R M Gapstur S M. Colon
cancer: a review of the epidemiology. Epidemiol Rev 1993;
15: 499-545.
(Revised version received June 1996)