| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communication |
Institut für Medizinische Statistik und Dokumentation der Johannes Gutenberg-Universität Mainz, D-55101 Mainz, Germany
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
From 1992–1997, three large-scale population-based case-control studies were conducted in Germany based on data from the nationwide German Childhood Cancer Registry. Data were collected using a self-administered questionnaire and subsequent telephone interviews with both parents. The interview was based on a structured questionnaire developed by the United States Children’s Cancer Group (2) but modified to assess country-specific issues. We provided a list of potential occupational exposures to certain chemicals, industrial dusts, and fumes to all parents.
Here we present results of analyses based on 1138 cases of ALL and 2962 controls that have been conducted to confirm or refute the findings of the United States report (1) . The strength of the findings of Shu et al. (1) would be considerably greater if the results of two comprehensive investigations featuring similar methodology but with different settings and independent populations were consistent.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The LSP started at the end of 1992 and was completed in 1996 (3–6) . The following diagnostic groups were considered: (a) acute leukemia; (b) lymphoma; (c) tumor of the central nervous system; (d) neuroblastoma; (e) nephroblastoma; (f) bone tumor; and (g) soft tissue sarcoma. Cases were eligible if they were newly diagnosed between July 1988 and June 1993 and if they lived within the boundaries of Lower Saxony at the date of diagnosis. We sampled two controls for each child with leukemia: (a) one control from the community where the diseased child lived; and (b) another control selected from a randomly selected community in Lower Saxony by a population-weighted sampling procedure. Additional matching criteria were gender and date of birth within 1 year. No controls were drawn for the group of cases with solid tumors.
The NIP study population consisted of children born after July 1, 1975 diagnosed with childhood acute leukemia or lymphoma between January 1980 and September 1994 who lived no more than 15 km (approximately 10 miles) from a German nuclear installation or in a matched control region at the date of diagnosis (7) . For all cases, one corresponding control matched for gender, date of birth within 1 year, and community was randomly selected from the respective population registration file.
The NIP and the WGP were conducted simultaneously between 1993 and 1997. The WGP consisted of the same diagnostic groups as the LSP (8–12) . Cases were included if the disease was diagnosed between October 1992 and September 1994 and if the child lived in West Germany at the date of diagnosis. Again, controls were drawn from the population registration file of the same community as the corresponding case and were matched for gender and date of birth within 1 year. Unlike the LSP, individual controls were chosen in the WGP for all cases, irrespective of their diagnosis.
The self-administered questionnaire used in all study parts listed a number of chemicals to which parents might have been occupationally exposed. This list contained four groups of chemicals and three groups of industrial dusts or fumes. The groups of chemicals were as follows: (a) solvents; (b) paints, thinners, colorants, or lacquers (referred to as paints or lacquers throughout this study); (c) oil products; and (d) pesticides. The groups of industrial dusts or fumes were as follows: (a) fumes from plastic or resin processing; (b) industrial dusts (e.g., from the coal or wood industry); and (c) fumes or dusts from metal melting. Mothers and fathers were asked the same questions for three different time of exposure windows: (a) during the year before conception; (b) during pregnancy; and (c) after birth.
The statistical approach for calculating pooled risk estimates for all study parts was to break matching status and use all available cases and controls. ORs and 95% CIs were then obtained by logistic regression models involving a posterior stratification for gender, age, and year of birth, with additional adjustments for degree of urbanization (urban, mixed, or rural) and socioeconomic status (high or other) (13) . Socioeconomic status was estimated by family net income and parental education. We also calculated ORs based on the original 1:1 matching by conditional logistic regression analysis. Both models were used to obtain ORs for the three individual study parts. In this report, we present the results for the first statistical approach. Results from the 1:1 matched analyses and study-specific results will be discussed if they reveal differences from the favored model that cannot be explained by random variability. All exposures were analyzed by time of exposure windows.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Table 1
presents demographic characteristics of ALL cases and total controls.
Controls were more likely to come from a family with a higher
socioeconomic status. Table 1
also shows that the WGP contributed about
one-half of all study cases and almost two-thirds of all study controls
to the analysis, whereas the LSP had the smallest study population.
Differences in the age distributions are due to controls who were
individual matches for cases with diagnoses other than ALL
(i.e., solid tumors) who, on average, were older than ALL
patients at the date of diagnosis. Because individual controls
for children with a solid tumor were sampled only in the WGP, this
study accounts for the entire difference in the age distribution of the
pooled study population.
|
presents the association of parental occupational exposures to certain
chemicals, industrial dusts, and fumes with childhood ALL risk. No
major differences between cases and controls were found for any
paternal occupational exposure to chemicals, plastic or resin fumes,
and metal melting. More case fathers reported being exposed to
industrial dusts; however, with ORs ranging between 1.2 and 1.3, the
association was rather weak. The highest risks of ALL were found to be
associated with maternal exposure to paints or lacquers during the
preconception period (OR, 1.6; 95% CI, 1.1–2.4) and during the index
pregnancy (OR, 2.0; 95% CI, 1.2–3.3). During the postnatal period,
the ALL risk was close to unity. Elevated ORs between 1.2 and 1.3 were
observed for maternal exposure to solvents during the preconception
period and index pregnancy. ORs for the preconception period and
gestation were also somewhat higher for exposure to oil products,
plastic or resin fumes, and industrial dusts; however, due to the
smaller number of subjects, the risk estimates were less
precise, and the CIs were wide.
|
The latter observation led us to examine the time pattern of prevalences of exposures. Whereas the interviews were conducted between 1992 and 1997, the dates of diagnosis ranged from 1980 to 1994 (however, for only 24.5% of all subjects, the date of diagnosis was before 1992). Therefore, it might have been difficult for the parents to remember substances that they were exposed to during the year before conception or during pregnancy. It might have been even more difficult for parents of controls to recall past occupational exposures, whereas parents of cases had probably already spent some time thinking about possible causes for the disease in their child. In fact, we observed a decline in prevalence of exposure for some of our potential risk factors with longer time periods between the date of the interview and the date of birth, but there were no differences between case and control groups. For maternal exposure to paints or lacquers, the prevalences of exposure for the shortest to the longest time lag between interview and birth (in steps of 3 years) were 4.4%, 5.5%, 4.6%, and 4.4% among ALL cases and 2.2%, 3.8%, 2.1%, and 2.0% among controls, respectively.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Differential bias, on the other hand, could result in bias of the OR
away from unity. This might occur if parents of children with cancer
were more sensitive to the perception of exposure. We already
discussed the possibility of recall bias when we found childhood
leukemia to be associated with self-reported parental occupational
exposure to pesticides (12)
. Therefore, we examined
whether the time lag between the time of exposure windows and the
interview date was associated with the prevalence of exposure and
whether this association was different for cases and controls. There
was no difference, particularly with regard to maternal exposure to
paints or lacquers. Furthermore, we examined the job titles of mothers
who claimed an occupational exposure to paints or lacquers:
(a) for 46.7% of mothers of ALL cases, an exposure seemed
plausible; (b) for 49.3% of mothers of ALL cases, exposure
did not clearly correspond to the job title but was not implausible;
and (c) for 4% of mothers of ALL cases, an occupational
exposure was not very likely. The respective percentages for mothers of
control children were 50.5%, 47.7%, and 1.8%. However, the benefit
of job titles as an instrument of validation is limited. As shown in
Table 2
, we found considerably more ORs > 1 than ORs < 1.
It must also be noted that among case families, the number of subjects
exposed to chemicals, dusts, and fumes during pregnancy was
consistently higher than the number of subjects exposed to chemicals,
dusts, and fumes during the postnatal period, whereas this was not true
among controls. Differential recall remains a concern, and a
more comprehensive exposure assessment, e.g., based on
exposure information from company records, is recommended.
However, the primary intention of this analysis was to compare the results of our study with those of the recent United States case-control study (1) . A moderately elevated risk of ALL with maternal exposure to paints or lacquers during the preconception period and during pregnancy was confirmed by our study. The biological plausibility of this finding has already been discussed in detail by Shu et al. (1) . With regard to the association between risk of ALL and maternal exposure to solvents, we observed the same tendency as seen in the United States study, but the associations in our study were weaker. Whereas Shu et al. (1) reported ORs between 1.6 and 1.8 for exposure during pregnancy and the preconception period, the respective ORs from our study were 1.2 and 1.3, and both studies observed no association during the postnatal period. A general pattern observed in both studies was that risk estimates were higher with regard to maternal occupational exposures as compared with paternal occupational exposures and that parental occupational exposures before birth were more relevant than exposures after birth. An additional finding was that the risk of ALL was not related to parental exposure to plastic and resin fumes, thus we failed to confirm an observation from the first study part that had been reported by Kaatsch et al. (3) .
In summary, this study suggests that maternal occupational exposure to paints or lacquers before birth is associated with an increased risk of childhood ALL. A small increase in ALL risk with paternal exposure to industrial dusts and maternal exposure to solvents should be investigated again in additional studies. However, this study also demonstrates the limitations of a commonly used interview-based method for assessing occupational exposure and indicates that future studies investigating the effects of past parental occupational exposure to certain substances need more specific exposure information and a validation of this exposure information.
|
Footnotes |
|---|
1 Supported by the German Federal Ministry for the
Environment, Reactor Safety and Nature Preservation (study part
conducted in West Germany and study part conducted in the vicinity of
nuclear installations), and the Ministry of Social Affairs of Lower
Saxony (study part conducted in Lower Saxony). 
2 To whom requests for reprints should be
addressed, at Institut für Medizinische Statistik und
Dokumentation der Johannes Gutenberg Universität Mainz, D-55101
Mainz, Germany. E-mail: schuez{at}imsd.uni-mainz.de
3 The abbreviations used are: ALL, acute
lymphocytic leukemia; OR, odds ratio; CI, confidence interval; LSP,
study part conducted in Lower Saxony; NIP; study part conducted in the
vicinity of nuclear installations; WGP; study part conducted in West
Germany.
Received 12/28/99; revised 5/17/00; accepted 6/ 6/00.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  L. E. Alderton, L. G. Spector, C. K. Blair, M. Roesler, A. F. Olshan, L. L. Robison, and J. A. Ross Child and Maternal Household Chemical Exposure and the Risk of Acute Leukemia in Children with Down's Syndrome: A Report from the Children's Oncology Group Am. J. Epidemiol., August 1, 2006; 164(3): 212 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A McKinney, N T Fear, and D Stockton Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study Occup. Environ. Med., December 1, 2003; 60(12): 901 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Schuz, L. G. Spector, and J. A. Ross Bias in Studies of Parental Self-reported Occupational Exposure and Childhood Cancer Am. J. Epidemiol., October 1, 2003; 158(7): 710 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Linet, S. Wacholder, and S. H. Zahm Interpreting Epidemiologic Research: Lessons From Studies of Childhood Cancer Pediatrics, July 1, 2003; 112(1): 218 - 232. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
