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Risk of childhood acute lymphoblastic leukaemia following parental occupational exposure to pesticides
  1. Deborah C Glass1,
  2. Alison Reid2,
  3. Helen D Bailey3,
  4. Elizabeth Milne3,
  5. Lin Fritschi2
  1. 1Monash Centre for Occupational and Environmental Epidemiology, Monash University, Melbourne, Victoria, Australia
  2. 2Western Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia, Australia
  3. 3Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia
  1. Correspondence to Dr Deborah C Glass, Monash Centre for Occupational and Environmental Epidemiology, Monash University, The Alfred Centre, Commercial Road, Melbourne, Victoria 3004, Australia; deborah.glass{at}monash.edu

Abstract

Objective To ascertain whether there was an association between parental occupational exposure to pesticides and increased risk of acute lymphoblastic leukaemia (ALL) in the offspring.

Method A population-based case–control study of childhood ALL was conducted in Australia. Information about the occupational pesticide exposure of mothers and fathers was collected using job-specific modules. Information on the types and extent of pesticide exposure was collected for mothers and fathers before and around the time of conception, and also for mothers during pregnancy for the index case or control and for 1 year after birth.

Results Paternal occupational exposure to pesticides before or around conception was not related to increased risk of childhood ALL. There was a low prevalence of occupational exposure to pesticides among women that reduced after birth.

Conclusions Paternal occupational exposure to pesticides was not found to be associated with an increased risk of acute lymphoblastic leukaemia in the offspring. The study was underpowered with respect to maternal exposure to pesticides.

  • Asbestos
  • benzene
  • cancer
  • epidemiology
  • exposure assessment
  • fire fighters
  • hygiene/occupational hygiene
  • migrant workers
  • paediatrics
  • retrospective exposure assessment
  • women

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What is known on this subject

  • Parental occupational exposure to pesticides before or around conception may be related to increased risk of childhood ALL.

What this paper adds

  • Parental occupational pesticide exposure may be linked to increased risk of childhood leukaemia.

  • In the period before conception and around childbirth, the prevalence of occupational exposure to pesticides among men in Australia is 15%. It is under 2% for women.

  • The risk of childhood ALL is not associated with paternal occupational exposure to pesticides.

Policy implications

  • Paternal occupational exposure to pesticides was not found to be associated with an increased risk of ALL in the offspring.

The aim of this study was to examine the risk of acute lymphoblastic leukaemia (ALL) among children of parents who had preconceptional, periconceptional and gestational or postnatal occupational exposure to pesticides determined by the expert exposure assessment method. This method is thought to be more objective than self-assessment.

ALL is the most common type of leukaemia in children and accounts for 75–80% of childhood leukaemias.1 ,2 The causes of childhood leukaemia are not well established but the initiation of leukaemia seems likely to require an interaction of environmental exposures and genetic factors.3

Meta-analyses have shown an association between childhood leukaemia and prenatal and postnatal maternal domestic (non-professional) pesticide exposure.4 ,5 In respect of occupational pesticide exposure, meta-analyses have shown an association between childhood leukaemia and prenatal maternal exposure2 but a weaker5 or non-significant2 association with paternal exposure. The parental exposure to pesticides has been shown to be associated with acute non-lymphocytic leukaemia and ALL.1

Methods

Aus-ALL was a population-based case–control study of ALL in children aged under 15 years in Australia, which took place between 2003 and 2006. Full details of the study population and recruitment methods used have been published elsewhere.6 ,7 Briefly, cases and their families were identified and recruited from 10 paediatric oncology centres in Australia and were eligible if they were diagnosed between 1 July 2003 and 31 December 2006 and were in remission. Three controls per case were recruited in seven recruitment waves over the same period, by random digit dialling, and were frequency matched to cases on age, sex and state of residence. The biological mother was required to have sufficient English language skills to complete the questionnaires for any potential case or control child to be eligible to participate. Human research ethics committee approval was obtained from all participating hospitals.

Written questionnaires seeking information on possible confounders including maternal and paternal age, smoking history etc. were completed by the parents. In addition, a lifetime occupational history up to the birth of the child for the father and up to 1 year after the birth of the child for the mother was collected. Information provided for each job included the year started and finished, the job title, the employer, main tasks and the number of hours worked each week. If the parent reported ever working in a job in which pesticide exposure was possible (eg, farmer), trained interviewers telephoned and asked the parent further specific questions about their job. This included information about the crops grown or the livestock handled, whether they used pesticides and the pest that they were used to control. The circumstances of use were also noted, for example, did they mix or spray the pesticide and what protective equipment did they use while handling the pesticides. The names of any pesticides that they recalled were noted.

An expert (DCG) reviewed the job histories and the answers to the job-specific questions to assess exposure to pesticides. She was blinded to case/control status and determined the likelihood of exposure (no exposure, possible exposure or probable exposure) to organophosphate insecticides, organochlorines, phenoxy herbicides, other herbicides, other pesticides. She also assessed the level of that exposure as high, medium or low. depending on the likelihood of individual inhalational and dermal exposure. Exposure was considered high if pesticides were mixed or sprayed without adequate PPE (gloves, respiratory protection and overalls). The use of adequate PPE, no mixing and no spraying was considered low exposure. The number of years in the job (duration of exposure) was determined from the job history.

Exposure variables were created for specific time periods (before and up to the child's birth and after the birth of the child (mothers only)) and for specific jobs (exposure in the jobs held 2 years before the birth of the child (mothers only) and exposures in the jobs held 1 year before the birth of the child (mothers and fathers)), in order to capture the exposure that occurred during the periods of pre and periconception, during gestation and post natally. Exposures for each time period were coded as none (no exposure), low (probable low exposure and possible low/medium/high exposure) and medium/high (probable medium or high exposure). Exposure variables in specific jobs up to 2 years and 1 year before the birth of the child were created by identifying the exposures in the job that was closest to the specified time period. Because of smaller numbers these variables were grouped as ‘not exposed’ and ‘exposed’. A variable indicating exposure to any pesticide was also created using the highest level of exposure to any of the individual pesticide groups.

The indicator used to assess socioeconomic status was the index of relative socioeconomic disadvantage (IRSD), one of the area-based measures calculated by the Australian Bureau of Statistics. The address at the time of study entry was linked to the 2006 census collection district (the smallest unit of population for which census information is available) and then to the corresponding IRSD. Further details of this process have been published elsewhere.6

Demographic and exposure variables were compared between cases and controls using χ2 tests and Fisher's exact tests.

The associations between maternal and paternal exposure and the risk of ALL in the offspring were investigated using logistic regression and adjusting for potential confounders (child sex, child age at diagnosis, socioeconomic status, parental smoking during birth year, and parental drinking alcohol 1 year before pregnancy, professional domestic pest control treatment and the maternal models also adjusted for maternal age). Models examined the relationship between occupational exposure at any time before and up to the birth of the child, in the job 2 years before the birth of the child, in the job 1 year before the birth of the child and in the period up to 1 year after the birth of the child. All analyses were undertaken using Stata V.10.1.

Results

Of 568 incident cases of ALL, 49 were ineligible to participate, leaving 519 eligible cases. Parents of 416 (80.2%) cases consented to participate in the study, and 378 mothers and 327 fathers provided occupational data. Of the 2947 known eligible control families identified through random digit dialling, 2071 (70.3%) agreed to take part. Because of age and sex quotas for frequency matching controls to cases, only 1361 of these families were actually recruited into the study and sent questionnaires. Of the recruited subjects, 854 mothers and 748 fathers provided occupational data. At least 1 JSM was completed by 98.7% of case mothers and 83% of case fathers, and by 97.3% of control mothers and 83.6% of control fathers.

Case mothers and fathers were slightly younger, drank less alcohol and were more likely to smoke cigarettes during pregnancy than did control mothers and fathers. There was no difference in socioeconomic disadvantage between case and control parents as measured by the IRSD of the residence. (table 1)

Occupational exposure to pesticides was uncommon. Approximately 15% of case and control fathers had probable exposure to pesticides before the birth of the child. In women, 1% of case mothers and 1.8% of control mothers were exposed at any time before the birth of the child. This fell to 0.1% or less after the birth.

There were no statistically significant associations between the risk of ALL in the offspring for maternal or paternal exposure to pesticides when examined as a whole or when examined by the broad type of pesticide, for any of the time periods we examined (table 2).

Table 1

Parental characteristics by case or control status

Table 2

Parental exposure to pesticides by case–control status

Discussion

This Australian national case–control study of childhood ALL used the best method available for assessing occupational exposure in a population-based study.8 We did not find an association between parental occupational exposure to pesticides and the risk of ALL in the child. This is consistent with the findings of two recent meta-analyses.1 ,2 Paternal exposure was found to be associated with an increased risk of leukaemia in a recent meta-analysis.5 We did not find a significantly increased risk.

The Aus-ALL study identified a modestly increased risk of ALL following domestic professional pest control treatments carried out during pregnancy and possibly during the child's early years.4 This was in line with two meta-analyses of domestic pesticide exposure4 ,5 and so this was adjusted for in our model. The initial survey contained detailed questions about domestic pesticide use. However, parents had difficulty recalling these details with any accuracy. For parents of older children, these questions would have involved recalling events up to 16 years ago. Because of the likelihood of measurement error, both in the frequency and timing of the exposures, these questions were removed.

It is possible that different pesticides were used to fumigate homes than were used by the mothers in their employment. It is likely that the exposure regimes at work and living in a treated home are also different. (Exposure in a home could have been for 24 h over some days compared with shorter-term use in the workplace and personal protective equipment may have been used at work but not at home).

Previous studies have found that worker-reports of their job histories are valid and reliable.9 ,11 We used the expert assessment method to assess occupational exposure to pesticides. Job title and information about how pesticide-related tasks were carried out were collected through the use of standardised questionnaires, rather than participants being asked to rate their exposure. This methodology leaves less room for recall bias compared with studies that rely on self-reported extent and frequency of exposure.8 ,12 As the exposure-circumstance information is specific to the participant, there will be less misclassification than when a job exposure matrix (JEM) is used to assess exposure. The available JEMs have not been validated for pesticides assessment in Australia. Pesticide use depends on the climate, crops and livestock and this is very region dependent. Benke et al (2001) found that FINJEM did not perform well in Australia with respect to pesticides.13

The main limitations of this study were the low prevalence of exposure among women, and the low participation fraction among controls in the study overall.

In conclusion we did not show an increased risk of acute lymphoblastic leukaemia in the offspring of fathers with occupational exposure to pesticides. However, a small over-all ALL risk cannot be ruled out from the current study results. The prevalence of maternal occupational exposure to pesticides was too low to draw any conclusions.

Acknowledgments

The authors would like to thank Derry Houston for allocating job-specific modules (JSM). Original JSM were provided by Patricia Stewart of NCI USA. The Aus-ALL consortium conducted the study and the Telethon Institute for Child Health Research (TICHR), University of Western Australia, was the coordinating centre. Bruce Armstrong (Sydney School of Public Health), Elizabeth Milne (TICHR), Frank van Bockxmeer (Royal Perth Hospital), Michelle Haber (Children's Cancer Institute Australia), Rodney Scott (University of Newcastle), John Attia (University of Newcastle), Murray Norris (Children's Cancer Institute Australia), Carol Bower (TICHR), Nicholas de Klerk (TICHR), Lin Fritschi (WA Institute for Medical Research), Ursula Kees (TICHR), Margaret Miller (Edith Cowan University), Judith Thompson (WA Cancer Registry) were the research investigators and Helen Bailey (TICHR) was the project coordinator. The clinical investigators were: Frank Alvaro (John Hunter Hospital, Newcastle); Catherine Cole (Princess Margaret Hospital for Children, Perth); Luciano Dalla Pozza (Children's Hospital at Westmead, Sydney); John Daubenton (Royal Hobart Hospital, Hobart); Peter Downie (Monash Medical Centre, Melbourne); Liane Lockwood, (Royal Children's Hospital, Brisbane); Maria Kirby (Women's and Children's Hospital, Adelaide); Glenn Marshall (Sydney Children's Hospital, Sydney); Elizabeth Smibert (Royal Children's Hospital, Melbourne); Ram Suppiah, (previously Mater Children's Hospital, Brisbane).

References

Footnotes

  • Funding The Aus-ALL study was funded by NHMRC. LF and EM were supported by NHMRC fellowships, HDB was supported by an NHMRC Post Graduate Scholarship.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Human research ethics committee approval was obtained from all participating hospitals.

  • Provenance and peer review Not commissioned; externally peer reviewed.