ORIGINAL ARTICLE

Helena Wennborg Jonathan Yuen Gun Nise

A.J. Sasco Harri Vainio Per Gustavsson
Cancer incidence and work place exposure among
Swedish biomedical research personnel
Received: 11 January 2001 / Accepted: 29 June 2001 / Published online: 14 September 2001
Springer-Verlag 2001
Abstract Objective: This cohort study aimed to elucidate
cancer occurrence in relation to occupational exposure
to specic chemical, biological and physical agents
among biomedical research laboratory personnel in
Sweden. Methods: Standardized incidence ratios (SIRs)
for the period 19701994 were calculated for specic
exposures in the laboratory group (n=3,277) and for
personnel working in non-laboratory departments
(n=2,011), as an internal reference group. Expected
numbers were based on national cancer rates.
Results: The total number of cancer cases was lower
than expected in both laboratory and non-laboratory
personnel. Elevated SIRs were noted for malignant
melanoma among female laboratory employees for
whom use was reported of solvents (SIR 2.73; CI 1.10
5.63) and of selected carcinogenic (International Agency
for Research on Cancer (IARC) group 2B) agents (SIR
3.15; CI 1.166.85). A light increase of the risk estimate
for breast cancer was also observed. Conclusions: In
general, there were few cases of cancer in this compar-
atively young cohort, but the ndings give some indi-
cation of increased risks for malignant melanoma in
female laboratory personnel after exposure to organic
solvents or substances classied by IARC as being
possibly carcinogenic.
Keywords Cancer Melanoma Breast cancer
Cohortstudy Laboratory personnel
Organic solvents
Introduction
A number of chemical, biological and physical agents in
biomedical research laboratory environments constitute
possible risk factors for cancer. A previous study of
cancer incidence and mortality in Swedish biomedical
laboratories showed a slightly increased standardized
incidence ratio (SIR) for brain tumors among male
laboratory personnel and breast cancer among female
scientists (Wennborg et al. 1999). Also in a number of
earlier studies, an excess of brain tumors (Belli et al.
1992; Cordier et al. 1995; Daly et al. 1994), as well as an
excess of breast cancer (Dosemeci et al. 1992; Belli et al.
1992) have been reported in association with laboratory
work, although a British study did not show any ele-
vated SIRs for these outcomes (Brown et al. 1996). An
increased SIR was observed for malignant melanoma
among female scientists in the above-mentioned Swedish
study (Wennborg et al. 1999) as well as among labora-
tory technicians in a study based on register information
Int Arch Occup Environ Health (2001) 74: 558564
DOI 10.1007/s004200100267
H. Wennborg (&)
Department of Biosciences, Unit for Environmental
Medicine, Novum Research Park,
Karolinska Institute, 141 57 Huddinge, Sweden
E-mail: helena.wennborg@biosci.ki.se
Fax: +46-8-6081501
H. Wennborg H. Vainio
The National Institute of Environmental Medicine,
Division of Health Risk Assessment,
Karolinska Institute, Stockholm, Sweden
J. Yuen
Department of Ecology and Crop Production Sciences,
Swedish University of Agricultural Sciences,
Uppsala, Sweden
G. Nise P. Gustavsson
Department of Occupational Health,
Karolinska Hospital, Stockholm, Sweden
G. Nise P. Gustavsson
Division of Occupational Health, Department
of Public Health Sciences, Karolinska Institute,
Stockholm, Sweden
A.J. Sasco
Unit of Epidemiology for Cancer Prevention,
International Agency for Research on Cancer,
Lyon, France
A.J. Sasco
Institut National de la Sante et de la Recherche
Me dicale, Lyon, France
H. Vainio
Unit for Chemoprevention, International
Agency for Research on Cancer, Lyon, France
from the Nordic countries (Andersen et al. 1999).
Elevated SIRs for all lymphohematopoietic tumors have
been described in a study of laboratory technicians ever
employed in laboratories of clinical chemistry, patholo-
gy or clinical genetics (Gustavsson et al. 1999), and in a
study of laboratory workers in Italy (Belli et al. 1992).
Some studies have also noted increased SIRs for pan-
creatic tumors in connection with laboratory work (Belli
et al. 1992; Cordier et al. 1995). A recently published
review about cancer risk in laboratory workers (Rachet
et al. 2000) concluded that the studies suggest a low
overall risk of cancer, albeit a higher risk may be
suggested for cancers of the pancreas and brain, and
non-Hodgkin's lymphoma.
Organic solvents have been studied in association
with cancer risk because of their common occurrence in
the laboratory environment and their potential carcin-
ogenic properties. Exposure to solvents in general has
been connected to increased risk of non-Hodgkin's
lymphoma (Vienna and Polan 1979; Olsson and Brandt
1988; Hardell et al. 1994). Formaldehyde has been
shown to cause nasal malignancies in the rat (Kamata
et al. 1996; Morgan 1997) and is currently classied as
probably carcinogenic (2A) to humans according to the
International Agency for Research on Cancer (IARC)
classication (IARC 1995).
This retrospective follow-up study was an extension
of the investigation about mortality and cancer inci-
dence among biomedical research laboratory personnel
in Sweden that was reported previously (Wennborg et al.
1999). The present study was performed to elucidate
cancer occurrence in laboratory personnel by using
questionnaire-collected, more-detailed, exposure infor-
mation i.e. use of specic biological, chemical and
physical agents in laboratories. Furthermore, the follow-
up time was 2 years longer than in the previous study.
Materials and methods
Cohort information and exposure assessment
The study base of the present investigation has been described in
detail (Wennborg et al. 1999). Briey, the cohort included 5,035
employees from laboratory departments and 2,923 from non-lab-
oratory departments at the Karolinska Institute and at the uni-
versities of Lund, Gothenburg and Linko ping, encompassing 70
laboratory and 34 non-laboratory departments, the latter included
as an internal reference group. For each individual the following
information was collected: name, Swedish personal identication
number also indicating gender, start and end dates for all em-
ployment periods, leaves of absence of 6 months or longer, work
positions, work places and changes of work places or work tasks.
This information was obtained from manual records from univer-
sities and, when available, from computerized records from the
universities and the Swedish National Government Employee
Salaries and Pension Board (SPV).
The present study is based on an exposure assessment by a
questionnaire directed to research group leaders. The director of
each institution was contacted and asked to compile a list of all
research group leaders in the department. The laboratory and non-
laboratory units, if they so wished, were visited for information
about the project by the study investigators. The questionnaires
were subsequently sent to all research group leaders in every par-
ticipating laboratory and non-laboratory department. In cases
where the group leader assessed that the methods used by personnel
in the current group diered markedly between the subgroups
within the unit, the research group was divided into two or several
new research groups according to the suggestions of the group
members, in order to obtain more homogenous exposures within
each research group. Retired research group leaders, or in some
cases other researchers, were also contacted to represent the re-
search groups which were no longer existing at the time of data
collection.
The total number of laboratory and non-laboratory research
groups participating in this study was 714, encompassing 5,288
individuals (3,277 laboratory personnel with 1,476 men and 1,801
women, 2,011 non-laboratory personnel with 1,290 men and 721
women), giving a participation proportion of 66.4% for the whole
cohort. This proportion was larger for personnel from non-labo-
ratory departments, 68.8%, than from laboratory departments,
65.1%.
The follow-up started in 1970 or with each employee's entry
into the cohort, if later, and lasted until 31 December 1994, death,
or until the last known date of employment for those lost to follow-
up (n=7), Table 1. Employees who had moved from a laboratory
department to a non-laboratory department were considered as
laboratory employees in the follow-up.
Most individuals participating in the study were directly
working in research; other occupations included are described in
the previous study about cancer mortality and incidence in labo-
ratory personnel (Wennborg et al. 1999). The minimum employ-
ment period was 1 year and the longest 20 years. The laboratory
personnel were slightly younger than the non-laboratory personnel
at entrance into the cohort (Fig. 1).
Exposure and questionnaire information
The questionnaire included items about chemical, biological and
physical agents such as chemicals, viruses, bacteria, plants and
organisms manipulated with recombinant-DNA techniques. The
chemical agents asked for were 74 of the most commonly used
Table 1 Number of subjects and vital status at the end of follow-up (1994), among laboratory and non-laboratory personnel at Swedish
University departments from 1970 to 1989
Vital status Laboratory departments Non-laboratory departments Total
Women % Men % Women % Men % Number %
Alive 1,715 95.2 1,355 91.8 691 95.8 1,229 95.3 4,990 94.4
Dead 53 3.0 77 5.2 18 2.5 37 2.9 185 3.5
Emigrated 31 1.7 40 2.7 12 1.7 23 1.7 106 2.0
Unknown 2 0.1 4 0.3 0 0.0 1 0.1 7 0.1
Total 1,801 100.0 1,476 100.0 721 100.0 1,290 100.0 5,288 100.0
559
chemicals in the laboratory environment. These included organic
solvents and agents classied as carcinogens according to IARC. A
possibility to add more chemicals was also oered in the ques-
tionnaire. Chemical and biological agents and techniques used in
biomedical laboratories were identied from method manuals used
in the 1970s and 1980s (Sambrook et al. 1989) and partly from the
questionnaire designed at IARC (Sasco 1994). Discussions with
safety personnel and the ad hoc registers of departments, if such
records existed, were used, and scientists with competence in
chemistry, immunology, molecular biology and toxicology gave
comments on the choice of agents and techniques in the ques-
tionnaire. The carcinogenic substances used in the laboratories
were categorized according to the IARC classication of carcino-
genic compounds: group 1 exposures carcinogenic to humans,
group 2A probably carcinogenic to humans and group 2B
possibly carcinogenic to humans (IARC 1998). An occupational
hygienist made a nal classication of solvents to be included. The
exposure during the period 19701989 was considered and collected
in subperiods of 5 years for each research group. If the group an-
nounced that some of the individuals within it had not been
working with certain specic agents, a new research group was
formed including these persons.
A pilot study was conducted at one of the laboratory depart-
ments showing that the use of this study questionnaire was feasible.
The exposure was dened for an individual from the reported ex-
posure data in that individual's research group after linkage with
the relevant work periods concurrent with the time of exposure.
The exposure categories included in the analyses were: work with
organic solvents, bacteria, radioactive isotopes, DNA, RNA,
formaldehyde, carcinogens according to IARC classication (1,
2A, 2B, or any of these), cell techniques and recombinant-DNA
techniques.
Classication and identication of cancer cases
Cancer cases were identied by record linkage to the cancer register
administrated by the Swedish National Board of Health and
Welfare. The Swedish personal identication number (``person
number''), which is unique to each individual living in Sweden, was
used for identication of cases diagnosed between 1 January 1970
and 31 December 1994, coded according to the ICD7 classication
system.
Statistical analysis
The SIR (Breslow and Day 1987) was calculated for each cancer
site in every exposure group for the laboratory departments and for
employees from non-laboratory departments. Only the cancer types
reported earlier in association with exposures similar to laboratory
environments, and most common cancers e.g. breast and prostate
cancers were included. The Swedish national cancer incidence rates
for the years 1970 to 1994 were used to calculate expected numbers.
All malignancies for each person were included in the calculations,
except in the analysis of total number of cancers, where only the
rst malignancy was taken into consideration. Person-year calcu-
lations were stratied for gender, age (5-year age groups) and
calendar time, calculated from 1 year after the introduction of a
specic potentially hazardous agent up to the date of cancer di-
agnosis (for all cancers, date of the rst cancer diagnosis), death,
emigration or until 31 December 1994, whichever came rst. For
the non-laboratory personnel, person-year calculations started
1 year from the start of the employment or from 1970 if started
earlier than 1969, and with the same follow-up as for the laboratory
personnel. Condence intervals (95% CI) were calculated, based on
the Poisson distribution (Gardner and Altman 1989). The DATAB
module of the EPICURE program package was used (HiroSoft,
Seattle, Wash., USA).
This study was approved by the local Ethics Committee at the
Karolinska Institute, Sweden and by the Swedish Data Inspection
Board.
Results
In general, the SIRs were low for all cancers together as
well as for most of the common cancer types for both
men and women in the laboratory and non-laboratory
groups. The total number of cancer cases in the present
subcohort was 178 (122 among laboratory and 56
among non-laboratory personnel).
The most commonly used carcinogens (including
several organic solvents) according to the IARC classi-
cation are shown in Table 2. The occurrence of the
most common cancer types and the cancer types that
were earlier reported as being possible outcomes in as-
sociation with exposures similar to those in the labora-
tory environment are shown, by use, in Table 3:
radioactive isotopes, solvents and formaldehyde among
laboratory personnel. For women who worked with
solvents, an elevated SIR of 2.73 (CI 1.105.63) was
obtained for malignant melanoma, based on seven cases,
but an increase in melanoma was also seen for the other
two agents. Use of radioactive isotopes produced an
elevated SIR of 1.26 (95% CI 0.154.54) for all lym-
phohematopoietic tumors among female laboratory
employees, but the number of cases was low (n=2).
Moreover, work with DNA techniques gave an in-
creased SIR of 1.75, CI 0.574.07 for breast cancer (six
cases), as did work with RNA, but the number of indi-
viduals using these techniques was approximately the
same. No other increased SIRs were seen in connection
with these agents (data not shown). The total number of
employees working with DNA was small (n=349).
Fig. 1 Age distribution of a laboratory and b non-laboratory
personnel at the time of entry into the cohort
560
Table 3 Occurrence of cancer by specic exposures: radioactive isotopes, solvents and formaldehyde among personnel working in
Swedish biomedical laboratories during 19701989 (O observed number of cases)
Agent Cancer Women Men
O SIR CI O SIR CI
Non-laboratory n=721 Women/1,290 men
All cancers 27 0.84 0.561.23 29 0.77 0.511.10
Lung 3 2.09 0.436.11 1 0.25 0.011.37
Breast/prostate 7 0.66 0.261.35 6 1.11 0.412.42
Malignant melanoma 2 1.25 0.154.51 5 2.07 0.674.82
Non melanoma skin 0 0
Urinary organs 1 1.74 0.049.70 1 0.37 0.012.04
Lymphohematopoietic 1 0.54 0.013.03 2 0.49 0.061.77
Radioactive
isotopes
n=844 Women/709 men
All cancers 20 0.72 0.441.11 13 0.67 0.351.14
Lung 0 3 1.56 0.324.56
Breast/prostate 9 0.95 0.431.79 2 0.76 0.092.76
Malignant melanoma 4 2.28 0.625.48 0
Non melanoma skin 1 2.53 0.0614.1 2 2.92 0.3510.5
Urinary organs 0 1 0.76 0.024.25
Lymphohematopoietic 2 1.26 0.154.54 0
Solvents n=1,173 Women/1,150 men
All cancers 38 0.85 0.601.17 30 0.71 0.481.02
Lung 0 4 0.91 0.252.33
Breast/prostate 17 1.13 0.661.81 7 0.98 0.392.02
Malignant melanoma 7 2.73 1.105.63 1 0.44 0.012.45
Non melanoma skin 1 1.44 0.048.03 3 1.85 0.385.41
Urinary organs 1 1.34 0.037.41 4 1.34 0.363.42
Lymphohematopoietic 2 0.76 0.092.75 1 0.23 0.011.30
Formaldehyde n=756 Women/741 men
All cancers 21 0.82 0.511.25 18 0.78 0.461.23
Lung 0 3 1.27 0.263.71
Breast/prostate 8 0.89 0.381.75 5 1.37 0.453.20
Malignant melanoma 4 2.52 0.696.44 0
Non melanoma skin 1 2.76 0.0715.4 2 2.33 0.288.40
Urinary organs 0 1 0.62 0.023.46
Lymphohematopoietic 1 0.69 0.023.83 1 0.41 0.012.30
Table 2 The most commonly used carcinogenic substances and solvents in biological research in Sweden in the 1970s and 1980s according
to classications of 1998 (n number of research groups)
Classication 19701974 19751979 19801984 19851989
(n) (n) (n) (n)
IARC 1 Benzene (62) Benzene (55) Benzene (61) Benzene (37)
Asbestos (19) Asbestos (22) Asbestos (18) Asbestos (14)
Benzidine (11) Benzidine (11) Benzidine (15) Benzidine (8)
IARC 2A Formaldehyde (113) Formaldehyde (144) Formaldehyde (189) Formaldehyde (207)
Acrylamide (40) Acrylamide (58) Acrylamide (93) Acrylamide (116)
Trichloroethylene (27) Trichloroethylene (29) Trichloroethylene (32) Trichloroethylene (26)
Benzo(a)pyrene (8) Benzo(a)pyrene (16) Benzo(a)pyrene (18) Benzo(a)pyrene (14)
MMS (4) Tetrachloroethylene (11) Tetrachloroethylene (10) Azacitidin (8)
IARC 2B Chloroform (101) Chloroform (124) Chloroform (150) Chloroform (168)
Trypan blue (43) Trypan blue (62) Trypan blue (78) Trypan blue (90)
Carbon tetrachloride (39) Carbon tetrachloride (48) Carbon tetrachloride (40) Dichloromethane (37)
Dioxane (36) Dioxane (32) Phenobarbital (34) Carbon tetrachloride (32)
Propylene oxide (21) 1,2-Dichloroethane (24) Dichloromethane (32) Phenobarbital (31)
Phenobarbital (20) Phenobarbital (23) Dioxane (29) Propylene oxide (26)
Hydrazine (14) Propylene oxide (22) 1,2-Dichloroethane (25) 1,2-Dichloroethane (24)
1,2-Dichloroethane (12) Dichloromethane (22) Propylene oxide (25) Hydrazine (23)
Dichloromethane (10) DDT (15) Hydrazine (17) Dioxane (21)
DDT (9) EMS (11) DDT (16) Mitomycin C (17)
o-Toluidine (9) Hydrazine (11) EMS (16) DDT (16)
EMS (8) o-Toluidine (11) Mitomycin C (13) EMS (11)
561
For men, elevated SIRs could be seen for non-mela-
noma skin cancer in connection with work with radio-
active isotopes (SIR 2.92, CI 0.3510.50; two cases) and
for formaldehyde (SIR 2.33, CI 0.288.40; two cases).
Work with formaldehyde also showed an increased SIR
for prostate cancer (SIR 1.37, CI 0.453.20; ve cases).
A slight increase in the SIR also existed for tumors in
urinary organs and for non-melanoma skin cancer in
association with use of organic solvents, SIR 1.34, CI
0.363.42; four cases, and SIR 1.85, CI 0.385.41; three
cases, respectively.
In Table 3, the SIRs for the same tumor types are
also given for the non-laboratory university personnel,
showing reduced SIRs for most of the cancer types.
However, an increased SIR, 2.07 (CI 0.674.82; four
cases) for malignant melanoma was also seen among
men working in non-laboratory departments.
Work with carcinogenic substances used in labora-
tories and the same cancer sites as above, are displayed
in Table 4. Use of carcinogens of group 2B was associ-
ated with an increased SIR for malignant melanoma for
female personnel to 3.15 (CI 1.166.85). The numbers of
cases of the other cancer types for female laboratory
workers by dierent exposure agents and techniques
were low.
Concerning the male personnel, a slightly elevated
SIR was seen for lung cancer with use of carcinogenic
substances group 1 (SIR 1.93, CI 0.405.65; three cases)
and for prostate cancer in association with exposure to
all IARC-classied substance groups; the SIR for group
1 was 1.28, for group 2A 1.21 and for group 2B 1.33.
Prostate cancer and use of recombinant-DNA tech-
niques gave a SIR of 1.79 (CI 0.494.59; four cases).
Data are not shown for other cancer types with use of
this agent.
Discussion
In comparison with the general population, the inci-
dence of most cancers was low in every exposure cate-
gory in the present cohort. Yet, for malignant melanoma
among female personnel working with organic solvents
an elevated SIR was obtained. However, the number of
cases was low, limiting the possibility of drawing con-
clusions about associations between laboratory expo-
sures and malignant melanoma. Furthermore, for breast
cancer among women working with DNA and RNA,
elevated SIRs were seen, but the numbers of cases were
also small. For the male laboratory personnel, slightly
elevated SIRs for prostate cancer in connection with
work with carcinogens and recombinant-DNA
techniques were obtained.
The participation proportion was somewhat lower in
the laboratory group than in the non-laboratory group,
which had also received the questionnaire. The reason for
sending the questionnaire to the non-laboratory groups
was to identify those employees who had previously
worked in laboratory departments. It should also be
noted that the research groups for four cases of
brain tumors previously identied in the study base
(Wennborg et al. 1999) never answered the questionnaire.
Table 4 Occurrence of cancer up to 1994, by each exposure group according to the IARC classications of carcinogenic substances,
among personnel working in Swedish biomedical laboratories during 19701989 (O observed number of cases)
Agent Cancer Women Men
O SIR CI O SIR CI
IARC 1 n=436 Women/393 men
All cancers 8 0.48 0.210.95 14 0.98 0.531.64
Lung 0 3 1.93 0.405.65
Breast/prostate 4 0.70 0.191.79 3 1.28 0.263.73
Malignant melanoma 2 2.02 0.257.31 1 1.22 0.036.77
Non melanoma skin 0 0
Urinary organs 0 1 0.95 0.025.31
Lymphohematopoietic 0 1 0.66 0.023.67
IARC 2A n=872 Women/794 men
All cancers 23 0.79 0.501.18 17 0.66 0.381.05
Lung 0 3 1.13 0.233.31
Breast/prostate 10 0.99 0.481.82 5 1.21 0.392.82
Malignant melanoma 4 2.21 0.605.65 0
Non melanoma skin 1 2.48 0.0613.8 2 2.08 0.257.53
Urinary organs 0 2 1.11 0.134.01
Lymphohematopoietic 0 1 0.37 0.012.07
IARC 2B n=927 Women/833 men
All cancers 23 0.72 0.461.08 18 0.65 0.381.02
Lung 0 2 0.70 0.082.52
Breast/prostate 9 0.85 0.391.60 6 1.33 0.492.88
Malignant melanoma 6 3.15 1.166.85 0
Non melanoma skin 1 1.95 0.5010.3 2 1.91 0.236.89
Urinary organs 0 2 1.02 0.123.70
Lymphohematopoietic 1 0.59 0.013.26 1 0.35 0.011.93
562
Moreover, the low risk estimates in general indicate
that there is a selection of healthy individuals in the
present study. This fact also shows that the general
population is not the optimal reference group to the
university laboratory employees.
The information about cancer cases can be consid-
ered as reliable; almost no cases should be missing, due
to the high validity of the Swedish Cancer Registry
(Mattsson 1984).
The exclusion of certain departments, e.g. organic
chemistry and physics, with hazardous occupational
exposures other than those in the present study, has
decreased the confounding eects from these agents.
There were no data about smoking in this study, but the
low occurrence of lung cancer in the previous study on
this cohort indicates that smoking can probably not be
considered as a potential confounder in these occupa-
tional groups (Wennborg et al. 1999). Moreover, the
frequency of smokers at the time of conception, ac-
cording to information collected by questionnaires and
from the medical birth register, was low in a study of
time-to-pregnancy among Swedish female laboratory
employees (Wennborg et al. 2001).
Exposures were assessed for research groups ac-
cording to the recommendations by IARC, since the
present investigation was part of an international mul-
ticenter study adhering to these criteria (Sasco 1992).
Collection of information was not considered feasible on
the individual level. Data collection performed in this
way precludes the gathering of information about some
potential confounders in the study, but this approach
made it possible to obtain exposure information about
the employees who had died during the follow-up. Some
of the group members may not have worked personally
with all types of agents reported in the questionnaire,
but the members of the research groups were working in
the same facilities and theoretically they could, there-
fore, have been exposed to the vapors and aerosols from
chemicals used in the laboratories.
No historic measurements of exposures were avail-
able and no measurements were performed during the
study. Measurements of current exposure conditions are
both expensive and complex, and do not reect past
exposure conditions. Problems in exposure assessment in
occupational studies with mixed chemical exposures are
widely discussed and some authors suggest the use of
biomarkers to improve the exposure assessment (Rachet
et al. 2000). The recombinant-DNA molecular biology
techniques were introduced broadly during the middle of
the 1980s, i.e. their use started relatively late during the
present follow-up. Because carcinogenic agents act at
both early and late stages, this might lead to underesti-
mation of cancer risk in cases where the induction time is
longer than the period that is being presently studied.
An elevated SIR was seen for malignant melanoma in
female employees in connection with work with solvents
and carcinogens, although the numbers of cases were
low. Elevated SIRs for malignant melanoma were also
found in previous occupational studies of laboratory
workers (Hoar and Pell 1981; Hunter et al. 1993; Va gero
et al. 1990) as well as among lithographers (Nielsen et al.
1996). Malignant melanomas are common among the
more auent social groups, possibly associated with
exposure to solar UV-light during holidays (Va gero et al.
1990). A Canadian study concluded that there is no
evidence of occupational risk for melanoma, but on the
other hand, all the studies conducted so far have been
too small for this conclusion to be denitive (Fritschi
and Siemiatycki 1996).
Several previous studies have found an excess of
lymphohematopoietic tumors among laboratory work-
ers (Belli et al. 1992; Brown et al. 1996). In a study on
mortality and cancer incidence among laboratory tech-
nicians in Sweden, an increased risk for this cancer type
was also observed (Gustavsson et al. 1999). That study
and the present one have a partly overlapping study
population of exposed individuals of 705 women and
men. However, in the material reported here, no ele-
vated SIR was seen for lymphohematopoietic malig-
nancies. The explanation is possibly related to
dierences in the study bases. No clinical departments
were included in the present study, and the lymphohe-
matopoietic tumors in the study by Gustavsson et al.
were found among women working in such laboratories,
e.g. of clinical chemistry, pathology or clinical genetics.
The previously reported study on this cohort showed
slightly elevated SIRs for breast cancer (Wennborg et al.
1999). In the present study, only weak associations in
connection with work with DNA or RNA was observed
(data not shown). Work with these techniques includes
use of organic solvents, such as phenol, chloroform
and isoamyl alcohol for extraction, as well as use of
ethidiumbromide for staining of nucleic acids.
The occurrences of cancer types for which elevated
SIRs have been observed in the present study as well as
in several previous studies (Belli et al. 1992; Cordier et al.
1995; Wennborg et al. 1999) dier between women and
men. There are two possible explanations: the exposures
are not similar for both sexes despite identical job titles,
or the mechanisms of carcinogenicity dier between
sexes (Blair et al. 1999; Docemeci et al. 1999).
Despite of the relatively small number of participat-
ing employees, which leads to a lack of power in the
study, there are other aspects to be considered. The
present cohort is relatively young and has been followed
for a limited period. Many employees have thus worked
for only a few years, which possibly mask a carcinogenic
eect of the exposures. However, work place safety
regulations in Sweden are very well dened and rea-
sonably well followed, which may reduce the exposure to
hazardous agents, e.g. with use of gloves, face masks,
fume hoods, exhaust work benches and restrictions in
handling of carcinogenic compounds.
In general and in connection with the specic agents
in the laboratory environment, the numbers of cancer
cases were small, producing wide condence intervals
but indicating that occurrence of most types of cancers
among Swedish laboratory employees is low. However,
563
increased SIRs were observed for malignant melanoma
in female laboratory employees using solvents.
Acknowledgements We are grateful to Professor Anders Ahlbom
for responsibility in the design of the study; to Professors Go sta
Axelsson and Bo Lambert for fruitful discussions and for critical
comments on the manuscript. We thank several scientists for
contributions to the denitions of laboratory methods and agents
during the planning of the study. Funding: The Swedish Medical
Research Council, the Swedish Cancer Society and the King
Gustav V Jubilee Clinic Cancer Research Foundation. The inter-
national study coordinator, Dr. Sasco at IARC, is supported by the
Europe against Cancer Programme (contracts 880516, 900061,
91CVV013130, 930998, 95201861 05F02), the DGV (contract
91CVVE20200) of the European Commission, the Ligue nationale
contre le Cancer and the direction Ge ne rale de la Sante (contract
9416) of France.
References
Andersen A, Barlow L, Engeland A, Kjrheim K, Lynge E, Puk-
kala E (1999) Work-related cancer in the Nordic countries.
Scand J Work Environ Health 25 [Suppl 2]:116
Belli S, Comba P, De Santis M, Grignoli M, Sasco AJ (1992)
Mortality study of workers employed by the Italian National
Institute of Health, 19601989. Scand J Work Environ Health
18:6467
Blair A, Zahm SH, Silverman DT (1999) Occupational cancer
among women: research status and methodologic consider-
ations. Am J Ind Med 36:617
Breslow NE, Day NE (1987) Statistical methods in cancer research.
Vol II, The design and analysis of cohort studies. IARC Sci
Publ 82:1406
Brown TP, Paulson J, Pannett B, Coupland C, Coggon D, Chilvers
CE, Sasco AJ (1996) Mortality pattern among biological
research laboratory workers. Br J Cancer 73:11521155
Cordier S, Mousel ML, Le Goaster C, Gachelin G, Le Moual N,
Mandereau L, Carrat F, Michaud G, Hemon D (1995) Cancer
risk among workers in biomedical research. Scand J Work
Environ Health 21:450459
Daly L, Herity B, Bourke GJ (1994) An investigation of brain
tumours and other malignancies in an agricultural research
institute. Occup Environ Med 51:295298
Dosemeci M, Alavanja M, Vetter R, Eaton B, Blair A (1992)
Mortality among laboratory workers employed at the US
Department of Agriculture. Epidemiology 3:258262
Dosemeci M, Cocco P, Chow WH (1999) Gender dierences in risk
of renal cell carcinoma and occupational exposures to chlori-
nated aliphatic hydrocarbons. Am J Ind Med 36:5459
Fritschi L, Siemiatycki J (1996) Melanoma and occupation: results
of a case-control study. Occup Environ Med 53:168173
Gardner MJ, Altman DG (1989) Statistics with condence. Con-
dence intervals and statistical guidelines. BMJ, London, p 140
Gustavsson P, Reuterwall C, Sadigh J, So derholm M (1999)
Mortality and cancer incidence among laboratory technicians in
medical research and routine laboratories (Sweden). Cancer
Causes Control 10:5964
Hardell L, Eriksson M, Degerman A (1994) Exposure to phen-
oxyacetic acids, chlorophenols, or organic solvents in relation
to histopathology, stage, and anatomical localization of
non-Hodgkin's lymphoma. Cancer Res 54:23862389
Hoar SK, Pell S (1981) A retrospective cohort study of mortality
and cancer incidence among chemists. J Occup Med 23:485
494
Hunter WJ, Henman BA, Barlett DM, Le Geyt IP (1993) Mortality
of professional chemists in England and Wales. Am J Ind Med
23:615627
International Agency for Research on Cancer (1995) IARC
monographs on the evaluation of carcinogenic risk to humans.
Vol 62, Wood dust and formaldehyde. International Agency for
Research on Cancer, Lyon, France
International Agency for Research on Cancer (1998) List of IARC
evaluations. http://193.51.164.11/monoeval/grlist.htm
Kamata E, Nakadate M, Uchida O, Ogawa Y, Kaneko T,
Kurokawa Y (1996) Eects of formaldehyde vapor on nasal
cavity and lungs of F-344 rats. J Environ Pathol Toxicol Oncol
15:18
Mattsson B (1984) Cancer registration in Sweden. Academic
Thesis, Karolinska Institute, Stockholm
Morgan KT (1997) A brief review of formaldehyde carcinogenesis
in relation to rat nasal pathology and human health risk
assessment. Toxicol Pathol 25:291307
Nielsen H, Henriksen L, Olsen JH (1996) Malignant melanoma
among lithographers. Scand J Work Environ Health 22:108
111
Olsson H, Brandt L (1988) Risk of non-Hodgkin's lymphoma
among men occupationally exposed to organic solvents. Scand
J Work Environ Health 14:246510
Rachet B, Partanen T, Kauppinen T, Sasco AJ (2000) Cancer risk
in laboratory workers: an emphasis on biological research. Am
J Ind Med 38:651665
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a
laboratory manual. 2nd edn. Cold Spring Harbor Laboratory
Press, New York
Sasco AJ (1992) Cancer risk in laboratory workers. Lancet 339:684
Sasco AJ (1994) International study of cancer risk in biology
research laboratory workers. Report no. 8. IARC, Lyon,
France
Va gero D, Swerdlow AJ, Beral V (1990) Occupation and malignant
melanoma: a study based on cancer registration data in
England and Wales and in Sweden. Br J Ind Med 47:317324
Vienna NJ, Polan A (1979) Lymphomas and occupational benzene
exposure. Lancet 1:13941395
Wennborg H, Yuen J, Axelsson G, Ahlbom A, Gustavsson P,
Sasco AJ (1999) Mortality and cancer incidence in biomedical
laboratory personnel in Sweden. Am J Ind Med 35:382389
Wennborg H, Bodin L, Vainio H, Axelsson G (2001) Solvent use
and time to pregnancy among female personnel in biomedical
laboratories in Sweden. Occup Environ Med 58:225231
564