Skip Navigation


American Journal of Epidemiology Advance Access originally published online on December 12, 2007
American Journal of Epidemiology 2008 167(5):598-606; doi:10.1093/aje/kwm339
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
167/5/598    most recent
kwm339v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by MacArthur, A. C.
Right arrow Articles by Theriault, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by MacArthur, A. C.
Right arrow Articles by Theriault, G. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Risk of Childhood Leukemia Associated with Vaccination, Infection, and Medication Use in Childhood

The Cross-Canada Childhood Leukemia Study

Amy C. MacArthur1, Mary L. McBride1,2, John J. Spinelli1,3, Sharon Tamaro1, Richard P. Gallagher1,2 and Gilles P. Theriault4

1 Cancer Control Research Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
2 Department of Health Care and Epidemiology, University of British Columbia, Vancouver, British Columbia, Canada
3 Department of Statistics, Simon Fraser University, Vancouver, British Columbia, Canada
4 Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montreal, Quebec, Canada

Correspondence to Mary McBride, Cancer Control Research Program, British Columbia Cancer Agency, Cancer Research Center, 2-107, 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3 (e-mail: mmcbride{at}bccrc.ca).

Received for publication May 22, 2007. Accepted for publication October 23, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Current hypotheses consonant with the peak in leukemia incidence in early childhood point to an infectious etiology. The authors examined the effect of postnatal exposures predicted to affect early immune functioning, including childhood vaccinations, illness, medication use, and breastfeeding patterns. Children 0–15 years of age diagnosed with leukemia from 1990 to 1994 and resident within principal cities across Canada were eligible for inclusion. Through pediatric oncology centers and population-based cancer registries, 399 cases were ascertained at the time of diagnosis. For each participating case, an age-, gender-, and area-matched control was randomly selected from government health insurance rolls. Risk factor information was obtained through personal interviews with each child's parents or guardians. Conditional logistic regression was used to calculate odds ratios, with adjustment for potential confounders. Use of immunosuppressant medication by the index child led to a deficit of risk (odds ratio = 0.37, 95% confidence interval: 0.16, 0.84), while vitamin intake was positively associated with leukemia (odds ratio = 1.66, 95% confidence interval: 1.18, 2.33). Breastfeeding for more than 6 months was also protective (p < 0.05). Results persisted for cases diagnosed with acute lymphoblastic leukemia and for children diagnosed at 1–5 years of age. These findings suggest a role for early immunologic challenge in the expression of childhood leukemia.

breast feeding; case-control studies; infection; leukemia, lymphocytic, acute, L1; risk factors; vaccination

Abbreviations: ALL, acute lymphoblastic leukemia; BCG, Bacillus Calmette-Guérin; CI, confidence interval; DTP, diphtheria, tetanus, and pertussis; MMR, measles, mumps, and rubella; OR, odds ratio


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
There have been recent advances in treatment and improvements in survival for childhood leukemia, yet its etiology remains largely unknown. The early incidence peak at ages 2–5 years points to disease mechanisms initiated prior to conception or during prenatal development. However, even if this is true, exposures incurred after birth may alter the expression of the disease in those with or without a specific genetic makeup or other predisposing characteristics (1).

Current hypotheses in the etiology of childhood leukemia suggest a role for immune development and response to infection, although a specific infectious agent has yet to be implicated. Greaves (2, 3) and Greaves and Alexander (4) postulated that exposure to common infections in infancy or early childhood could lead to improved immunologic resistance during subsequent challenges, while delayed exposure could lead to an aberrant response resulting in leukemia among children who had not otherwise developed immunity. Support for an infectious etiology has also been provided from studies of space-time clustering and population mixing (5–11). However, the evidence remains inconclusive, and results from case-control studies of postnatal exposures and immune susceptibility factors, including infections, vaccination, breastfeeding, and social mixing, have been contradictory (5, 12, 13). The inconsistency in results across studies may reflect differences in control selection, statistical power, and histologic subtypes of leukemia investigated.

As part of a five-province consortium across Canada, we evaluated the association between childhood leukemia and a variety of clinical, environmental, and genetic risk factors. Study findings have previously shown no relation between electromagnetic fields and risk of childhood leukemia (14). This analysis explores the effect of exposures incurred after birth to determine risk associated with factors affecting early immune development, including childhood vaccination, illness, medication use, and infant breastfeeding.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Study population and data collection
Children aged 0–14 years, diagnosed with leukemia between January 1, 1990, and December 31, 1994 (June 30, 1995, in British Columbia and Quebec), and resident within 100 km of the principal cities of Alberta (Edmonton and Calgary), British Columbia (Vancouver and Victoria), Saskatchewan (Saskatoon), Manitoba (Winnipeg), and Quebec (Montreal) were eligible for inclusion in the study. Participants meeting these criteria were ascertained through pediatric oncology treatment centers in each of the five provinces. Population-based cancer registries were also used for case ascertainment in all provinces except Quebec. Residential eligibility criteria were defined as living within a census tract area within 100 km of one of the study sites. The centroid of each census tract was defined as the geographic center of each city's regional health area. During the first year of the study, ascertainment was retrospective. From 1991 forward, cases were approached within 6 weeks after diagnosis and notification from pediatric oncology centers. All diagnoses were verified through receipt of hematology and pathology reports, and residential eligibility was verified at the time of initial contact with the child's parents or guardians. Provincial cancer registry records were also reviewed on a continuing basis to ensure that cases were not missed. Cases with Down's syndrome, an associated genetic condition, were deemed ineligible because of the known relation with leukemia.

For each participating case, an age-, gender-, and area-matched (based on residence within the same census tract) control was randomly selected from the provincial government health insurance rolls. Each insurance roll included virtually the entire provincial population with the exception of those residing in the province less than 3 months. In Quebec, family allowance rolls were used in addition to government insurance lists for control selection during the first 2 years of the study. Since application for family allowance results in financial benefits, registration of new births is complete. Matching on age was within 6 months for cases diagnosed at age 2 years or older and within 3 months for cases diagnosed before 2 years of age. Initial contact with potential controls was by letter, followed by telephone contact. In total, 449 cases and 675 controls were identified as possible subjects. Of these, 445 cases and 526 controls eligible for inclusion in the study were successfully contacted. A total of 399 case-control pairs agreed to participate, resulting in contact participation rates of 90 percent for eligible cases and 76 percent for eligible controls.

Risk factor information was obtained through standardized, personal interviews conducted in the home with the child's parents or guardians. Whenever possible, interviews were conducted with both parents together, and interpreters were available if the subject's family spoke neither English nor French. Information was collected on specific vaccinations, illnesses, and medication use in childhood, including the age at first exposure and duration of exposure (for medication use). Immunization data were recorded from the child's vaccination record if available at the time of interview. Otherwise, parents were asked to recall their child's immunization history. Parents were also asked about the index child's feeding patterns at specific ages during the first year of life, and whether this included exclusive breastfeeding or milk supplementation. Interviewers were not informed of the case-control status of the child; however, blinding could not be ensured since interviewers may have become aware of the disease status of the child during the interview.

Data analysis
Risk factors for childhood leukemia were examined by use of standard case-control methods (15). Pearson's chi-square was used to compare demographic and socioeconomic characteristics between cases and controls. Conditional logistic regression was used to estimate odds ratios and 95 percent confidence intervals as approximations of relative risks, with adjustment for potentially important confounding variables deemed significant (p < 0.05 or odds ratio (OR) ≥ 1.5 and p < 0.10) in a preliminary exploration of the data, including maternal education, annual household income, ethnicity, maternal age at birth, and number of residences since birth. The multivariate models relied on strata formed by the following matching factors: province, gender, and age (<1.5, 1.5–4, 5–9, and 10–14 years). This stratified analysis proved to be more efficient than a matched analysis, and it avoided loss of information due to cases that could not be matched to a comparable control subject. Exposures that occurred within 6 months of diagnosis (pseudodiagnosis in controls) were not counted during analyses. Results are presented for the overall study group, as well as for cases diagnosed with acute lymphoblastic leukemia (ALL). We also examined risk according to the timing of exposure (those occurring within the first year of life and later) and for different age groups (those diagnosed at 1–5 years and 6–14 years). Statistically significant risk factors for childhood leukemia were indicated by a significance level of p < 0.05 (two-sided test). Tests for trend for continuous predictor variables were also conducted with statistical significance indicated by p < 0.05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
The majority of cases in our study were diagnosed with ALL (88 percent), followed by acute myeloid leukemia (10 percent) and other non-ALL subtypes (2 percent). The distribution of subtypes across age strata reveals that most cases of ALL were diagnosed among children 1–5 years of age (65 percent), while the majority of non-ALL cases were diagnosed in infants less than 1 year of age or children aged 6–14 years (69 percent).

As presented in table 1, cases and controls were comparable according to their age and gender distribution because of study selection criteria. However, cases had a lower overall socioeconomic status (as measured by parental income and education) and had lived in more residences prior to diagnosis than had control subjects. There was also a higher proportion of case mothers who gave birth to the index child at a younger age, particularly before the age of 25 years.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Characteristics of cases and controls, the Cross-Canada Childhood Leukemia Study, 1990–1994

 
Information on the child's medical history allowed for examination of the relation between childhood leukemia and immunization, illness, and medication use. No association was found between childhood leukemia and exposure to several common vaccines, including the measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTP), poliomyelitis, hepatitis, or Bacillus Calmette-Guérin (BCG) vaccines, although the number of unvaccinated (or vaccinated for hepatitis and BCG) subjects was very small for some groups (table 2). Although it is expected that the proportion of subjects unexposed to MMR, DTP, and poliomyelitis vaccines would be low because of Canada's national immunization strategy, these results should be interpreted with caution. Assessment of risks for ALL subtypes or by age at diagnosis did not change our findings. However, a nonsignificant inverse association with leukemia was observed for children that received the MMR vaccine after 1 year of age, with odds ratios approaching a 50 percent deficit of risk (for measles: OR = 0.49, 95 percent confidence interval (CI): 0.20, 1.18; for mumps: OR = 0.43, 95 percent CI: 0.18, 1.02; and for rubella: OR = 0.51, 95 percent CI: 0.23, 1.12). Information on exposure to each vaccine was collected separately, and if the child's immunization record was not available at the time of interview, parents were asked to recall their child's vaccination history. Therefore, a different proportion of parents responded that the index child had received each of the three vaccines when, in fact, the MMR vaccine is administered as one shot in combination.


View this table:
[in this window]
[in a new window]

  		TABLE 2. Vaccinations in childhood and risk of childhood leukemia, the Cross-Canada Childhood Leukemia Study, 1990–1994

 
Several illnesses and common infections in childhood, including measles, mumps, rubella, chicken pox, and ear infections, were not associated with leukemia in the overall study group or among cases diagnosed with ALL (table 3). No relation between illness in childhood and childhood leukemia was found when data were examined according to age at diagnosis or timing of exposure (data not shown).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Illness and infection in childhood and risk of childhood leukemia, the Cross-Canada Childhood Leukemia Study, 1990–1994

 
With respect to medication use, an excess risk of leukemia was observed among children that had ever taken vitamin supplements (OR = 1.66, 95 percent CI: 1.18, 2.33) (table 4). Conversely, use of immunosuppressant medication, including cortisone, prednisone, mercaptopurine, cytoxan, and imuran, led to a decreased risk of leukemia (OR = 0.37, 95 percent CI: 0.16, 0.84). Both of these relations persisted when risk was examined separately for ALL subtypes (table 4) and for exposures during the first year of life and later (data not shown). However, vitamin supplementation was predictive of risk only among children diagnosed in early childhood (OR = 2.06, 95 percent CI: 1.31, 3.25) and not among children diagnosed after 5 years of age (p > 0.05) (data not shown). Several other common prescription drugs (blood pressure medication, hormones, thyroid medications, antiepileptic drugs, and sedatives) and over-the-counter medications (diuretics, diet pills, and antiinflammatory medications) were examined but either showed no significant relation with childhood leukemia or had too few cases to allow for meaningful interpretation of the results (data not shown). Information on indications for the use of specific medications taken by the index child was not available.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Vitamin supplementation and medication use in childhood and risk of childhood leukemia, the Cross-Canada Childhood Leukemia Study, 1990–1994

 
The results of an analysis of infant feeding patterns are shown in table 5. The model, adjusted for maternal age at birth and socioeconomic status, showed milk supplementation to be positively associated with childhood leukemia. The relation was strongest among infants 7–12 months of age who had received milk supplementation more than 50 percent of the time (OR = 1.79, 95 percent CI: 1.11, 2.89). However, a longer duration of exclusive breastfeeding was not suggestive of a protective effect (p > 0.05).


View this table:
[in this window]
[in a new window]

  		TABLE 5. Infant feeding patterns and risk of childhood leukemia, the Cross-Canada Childhood Leukemia Study, 1990–1994

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Greaves (2) and Greaves and Alexander (4) have proposed that factors that elicit an immune response in infancy or early childhood, including exposure to common infections, could be protective for childhood leukemia. Our study was designed to identify postnatal factors associated with childhood leukemia that might test this theory, including exposure to common illnesses, immunization, medication use, and breastfeeding. After adjustment for socioeconomic status and other maternal reproductive factors, a negative association between use of immunosuppressant medications in childhood and breastfeeding for longer than 6 months was observed. Conversely, use of vitamins in early childhood led to an increased risk of childhood leukemia.

Studies of vaccination in infancy or early childhood have generally reported a protective effect on the risk of childhood leukemia (16–19), although findings vary according to the type of vaccine and the age at immunization. Decreased risks of leukemia have been associated with measles vaccination (16), DTP vaccination (17), Haemophilus influenzae type B (Hib) vaccination (20–22), and BCG vaccination for tuberculosis (16). Timely completion of early childhood immunizations may decrease the risk of leukemia through general improvements in immune functioning (2, 4). Vaccination in childhood would also be consistent with higher levels of herd immunity (natural immunization), which may also reduce risk (7, 23). We observed a protective effect of MMR vaccination on childhood leukemia risk, but only among children immunized after 1 year of age, and odds ratios were only marginally significant (p < 0.10). Results persisted after adjustment for indicators of socioeconomic status, suggesting that control selection bias was not responsible for our findings. Any residual confounding by socioeconomic status is unlikely given that routine childhood immunizations are delivered universally under a publicly funded health-care system in Canada. However, the proportions of cases and controls receiving each of the three vaccines were not identical, which points to the possibility of exposure misclassification since MMR is administered as a combination vaccine. There were also a very small number of unvaccinated subjects, which further limits interpretation of our findings.

Support for an infectious etiology for childhood leukemia has also been derived from studies of early illness and common childhood infections. Although no one infectious agent has been identified, decreased risks of leukemia have been reported among children with prior measles, mumps, hepatitis A, and ear infections, as well as nonspecific viral infections (16, 18, 24–26). We found no association between childhood leukemia and any of these illnesses or infections. It is plausible that differences in the age at infection, type of infection, and timing of exposure could account for the divergent trends across studies. For instance, Chan et al. (27) reported a decreased risk of leukemia following infectious exposure during the first year of life, while infection in the year prior to diagnosis led to an increased risk. Others have observed a similar protective effect of infection during the first year of life (25, 28) or through early childhood (26), but not among older children. We measured illness from birth to diagnosis, and separately for exposures during the first year of life and later, with no indication that risk was related to a critical window of exposure.

Our study is one of but a few studies to examine the potential effects of early medication use on the risk of childhood leukemia. The use of chloramphenicol antibiotics has previously been shown to increase risk for both the ALL and acute nonlymphocytic leukemia subtypes in a case-control study from China (29), but we could not confirm this association because too few cases (n = 1) and controls (n = 2) had reported use of chloramphenicol. Our study also showed no association between childhood leukemia and common medications such as aspirin and allergy remedies. Although cautionary because of small numbers, a protective effect was observed for use of immunosuppressant medications in childhood, which would lower the body's natural defense system, thereby leading to an increased susceptibility to infection and possibly early immunologic challenge. A positive relation between childhood leukemia and use of vitamin supplements also supports a role for immune development in the etiology of childhood leukemia. Because controls were of a higher socioeconomic status than cases, it is possible that control participation bias may have influenced these results. However, it is expected that children of higher socioeconomic status would have better access to nutritional supplements than children of lower socioeconomic households, which would bias our result toward the null. Furthermore, our findings were strengthened owing to the persistence of significant relations when risk was examined for ALL subtypes, for children diagnosed in early childhood, and for exposures occurring within the first year of life and later.

Several studies have shown a protective effect of prolonged breastfeeding on risk of childhood leukemia (26, 30–33), although results remain equivocal (5, 18, 19, 34, 35). We found that mixed feeding with a higher proportion of milk supplement (breast milk + >50 percent milk supplementation) after 6 months of age led to an increased risk of childhood leukemia in comparison with exclusive breastfeeding. Human milk contains an array of microbial activity, and it is postulated that breastfed infants are less susceptible to infection because of early development of the immune system in comparison with artificially fed infants (2, 4, 35). Breastfed infants may also be exposed to infectious agents transferred from the mother's milk, thereby leading to early exposure to infectious organisms and development of natural antibodies (35). We found the relation with milk supplementation to be more pronounced for infants 7–12 months of age compared with early infancy, although a longer duration of exclusive breastfeeding was not associated with greater sustained protection.

Inherent in our case-control study is the possibility of selection or recall bias, as well as exposure misclassification, since information was not always corroborated with the index child's vaccination or medical records. We improved upon traditional retrospective designs by collecting risk factor data close to the time of diagnosis, thereby minimizing loss to follow-up. We also ensured essentially complete ascertainment of cases from cancer registries, acute-care hospitals, cancer treatment centers, and hematology and pathology laboratories. Controls were selected from population-based health insurance claims as part of the provincially administered public health system in Canada, resulting in a representative sample of study participants. However, given the large number of statistical tests conducted, some of our results might be chance findings from multiple comparisons.

In conclusion, our study highlights a potential role for immune development in the expression of childhood leukemia. Our results are congruent with the current hypothesis put forth by Greaves that states that reduced antigenic challenge during early postnatal development may contribute to an increased risk of childhood leukemia (36). Information on risks associated with immunosuppressant medication and vitamin supplementation in relation to the timing of exposure (infancy vs. later childhood) strengthens the interpretation of our results in accordance with Greaves' hypothesis. Nonetheless, these relations need to be investigated further with respect to possible mechanisms of induction and to explicate potential interactions with other predisposing characteristics, in both the perinatal and the postnatal stages of development.


   ACKNOWLEDGMENTS
 
Funding for this study was provided by the National Health Research and Development Program of Health Canada and the Canadian Electricity Association. Additional funding for one of the authors (A. C. M.) was provided by a research unit infrastructure grant from the Michael Smith Foundation for Health Research.

The authors would also like to acknowledge the substantial contributions of the registry and epidemiologic support staff at the provincial cancer organizations (the British Columbia Cancer Agency, the Alberta Cancer Board, the Saskatchewan Cancer Agency, and the Manitoba Cancer Treatment and Research Foundation), the pediatric oncology centers, and McGill University.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Chow W, Linet MS, Liff JM, et al. Cancers in children. In: Cancer epidemiology and prevention—Schottenfeld D, Fraumeni JF Jr, eds. (1996) New York, NY: Oxford University Press. 1331–69.
  2. Greaves MF. Speculations on the cause of childhood acute lymphoblastic leukemia. Leukemia (1988) 2:120–5.[Web of Science][Medline]
  3. Greaves MF. Aetiology of acute leukaemia. Lancet (1997) 349:344–9.[CrossRef][Web of Science][Medline]
  4. Greaves MF, Alexander FE. An infectious etiology for common acute lymphoblastic leukemia in childhood. Leukemia (1993) 7:349–60.[Web of Science][Medline]
  5. Little J. Epidemiology of childhood cancer. (1999) Lyon, France: International Agency for Research on Cancer. (IARC scientific publication no. 149).
  6. Kinlen LJ. Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain. Lancet (1988) 2:1323–7.[CrossRef][Web of Science][Medline]
  7. Kinlen LJ. Epidemiological evidence for an infective basis in childhood leukemia. Br J Cancer (1995) 71:1–5.[Web of Science][Medline]
  8. Kinlen LJ, Balkwill A. Infective cause of childhood leukaemia and wartime population mixing in Orkney and Shetland, UK. (Letter). Lancet (2001) 357:858.[CrossRef][Web of Science][Medline]
  9. McNally RJ, Eden TO. An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br J Haematol (2004) 127:243–63.[CrossRef][Web of Science][Medline]
  10. Kinlen LJ, O'Brien F, Clarke K, et al. Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland, including the area near Dounreay nuclear site. BMJ (1993) 306:743–8.[Abstract/Free Full Text]
  11. Kinlen LJ, Stiller C. Population mixing and excess of childhood leukemia. (Letter). BMJ (1993) 306:930.[Free Full Text]
  12. Linet M, Wacholder S, Zahm SH. Interpreting epidemiologic research: lessons from studies of childhood cancer. Pediatrics (2003) 112:218–32.[Free Full Text]
  13. Petridou E, Trichopoulos D. Leukemias. In: Textbook of cancer epidemiology—Adami HO, Hunter DH, Trichopoulos D, eds. (2002) New York, NY: Oxford University Press. 556–72.
  14. McBride ML, Gallagher RP, Theriault G, et al. Power-frequency electric and magnetic fields and risk of childhood leukemia in Canada. Am J Epidemiol (1999) 149:831–42.[Abstract/Free Full Text]
  15. Breslow NE, Day NE. Statistical methods in cancer research. Vol I. The analysis of case-control studies. (1980) Lyon, France: International Agency for Research on Cancer. (IARC scientific publication no. 32).
  16. Nishi M, Miyake H. A case-control study of non-T cell acute lymphoblastic leukaemia of children in Hokkaido, Japan. J Epidemiol Community Health (1989) 43:352–5.[Abstract/Free Full Text]
  17. McKinney PA, Cartwright RA, Saiu JM, et al. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma. Arch Dis Child (1987) 62:279–87.[Abstract/Free Full Text]
  18. Kaatsch P, Kaletsch U, Krummenauer F, et al. Case control study on childhood leukemia in Lower Saxony, Germany: basic considerations, methodology, and summary of results. Klin Padiatr (1996) 208:179–85.[Web of Science][Medline]
  19. Hartley AL, Birch JM, McKinner PA, et al. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer. J Epidemiol Community Health (1988) 42:235–42.[Abstract/Free Full Text]
  20. Groves F, Auvinen A, Hakulinen T. Haemophilus influenzae type B vaccination and risk of childhood leukemia in a vaccine trial in Finland. (Abstract). Ann Epidemiol (2000) 10:474.[Medline]
  21. Groves FD, Gridley G, Wacholder S, et al. Infant vaccinations and risk of childhood acute lymphoblastic leukaemia in the USA. Br J Cancer (1999) 81:175–8.[CrossRef][Web of Science][Medline]
  22. Auvinen A, Hakulinen T, Groves F. Haemophilus influenzae type B vaccination and risk of childhood leukaemia in a vaccine trial in Finland. Br J Cancer (2000) 83:956–8.[CrossRef][Web of Science][Medline]
  23. Kinlen LJ. Infection and childhood leukemia. Cancer Causes Control (1998) 9:237–9.[CrossRef][Web of Science][Medline]
  24. Smith MA, Simon R, Strickler HD, et al. Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene conditions. Cancer Causes Control (1998) 9:285–98.[CrossRef][Web of Science][Medline]
  25. Neglia JP, Linet MS, Shu XO, et al. Patterns of infection and day care utilization and risk of childhood acute lymphoblastic leukaemia. Br J Cancer (2000) 82:234–40.[CrossRef][Web of Science][Medline]
  26. Perrillat F, Clavel J, Auclerc MF, et al. Day-care, early common infections and childhood acute leukaemia: a multicentre French case-control study. Br J Cancer (2002) 86:1064–9.[CrossRef][Web of Science][Medline]
  27. Chan LC, Lam TH, Li CK, et al. Is the timing of exposure to infection a major determinant of acute lymphoblastic leukemia in Hong Kong? Paediatr Perinat Epidemiol (2002) 16:154–65.[CrossRef][Web of Science][Medline]
  28. Jourdan-Da Silva N, Perel Y, Mechinaud F, et al. Infectious diseases in the first year of life, perinatal characteristics and childhood acute leukaemia. Br J Cancer (2004) 90:139–45.[CrossRef][Web of Science][Medline]
  29. Shu XO, Gao YT, Linet MS, et al. Chloramphenicol use and childhood leukaemia in Shanghai. Lancet (1987) 2:934–7.[Web of Science][Medline]
  30. Infante-Rivard C, Fortier I, Olson E. Markers of infection, breast-feeding and childhood acute lymphoblastic leukaemia. Br J Cancer (2000) 83:1559–64.[CrossRef][Web of Science][Medline]
  31. Shu XO, Linet MS, Steinbuch M, et al. Breast-feeding and risk of childhood acute leukemia. J Natl Cancer Inst (1999) 91:1765–72.[Abstract/Free Full Text]
  32. Berel V, Fear NT, Alexander F, et al. Breastfeeding and childhood cancer. Br J Cancer (2001) 85:1685–94.[CrossRef][Web of Science][Medline]
  33. Kwan ML, Buffler PA, Abrams B, et al. Breastfeeding and the risk of childhood leukemia: a meta-analysis. Public Health Rep (2004) 119:521–35.
  34. Petridou E, Trichopoulos D, Kalaothaki V, et al. The risk profile of childhood leukaemia in Greece: a nationwide case-control study. Br J Cancer (1997) 76:1241–7.[Web of Science][Medline]
  35. Davis MK. Review of the evidence for an association between infant feeding and childhood cancer. Int J Cancer Suppl (1998) 11:29–33.[Medline]
  36. Greaves MF. Pre-natal origins of childhood leukemia. Rev Clin Exp Hematol (2003) 7:233–45.[Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am J EpidemiolHome page
D. A. Hanauer and S. W. Choi
RE: "RISK OF CHILDHOOD LEUKEMIA ASSOCIATED WITH VACCINATION, INFECTION, AND MEDICATION USE IN CHILDHOOD: THE CROSS-CANADA CHILDHOOD LEUKEMIA STUDY"
Am. J. Epidemiol., August 1, 2008; 168(3): 353 - 353.
[Full Text] [PDF]

Home page
 Am J EpidemiolHome page
A. C. MacArthur and M. L. McBride
THE FIRST TWO AUTHORS REPLY
Am. J. Epidemiol., August 1, 2008; 168(3): 353 - 354.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
167/5/598    most recent
kwm339v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by MacArthur, A. C.
Right arrow Articles by Theriault, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by MacArthur, A. C.
Right arrow Articles by Theriault, G. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?