Is the timing of exposure to infection a major determinant of acute lymphoblastic leukaemia in Hong Kong?

Abstract

The hypothesis that protection of infants from exposure to infectious agents with delayed first exposure to one or more specific agents together contribute to the aetiology of childhood leukaemia, especially common acute lymphoblastic leukaemia (cALL), has substantial indirect support from descriptive epidemiology and case-control studies in developed Western countries. A case-control study of childhood leukaemia diagnosed at ages 2-14 years has now been conducted in Hong Kong. Cases (n=98) formed a consecutive series of Chinese children diagnosed with acute leukaemia; controls (n=228) were identified following a survey using random digit dialling and required to attend for medical examination by a paediatrician. Interviews with mothers were conducted in hospital by one trained interviewer using a structured questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) are reported for exposure variables capable of serving as proxies for exposure to infection in two critical time periods: first year of life, year before reference date (diagnosis for cases, corresponding date for controls). Analyses used logistic regression with adjustment for appropriate confounders. Change of area of residence reduced risk if during the first time period (OR = 0.47 [95% CI 0.23, 0.98]) and increased risk if during the second (OR=3.92, [95% CI 1.47, 10.46]). Reported roseola and/or fever and rash in the first year of life reduced risk (OR=0.33 [95% CI 0.16, 0.68]) whereas tonsillitis in the period 3-12 months before reference date increased risk (OR=2.56 [95% CI 1.22, 5.38]). Some other proxies for exposure to infection at the critical times were associated with predicted patterns of risk but day-care attendance failed to show predicted associations. These results provide support for the delayed exposure hypothesis in an affluent geographical setting in which population exposure to infectious agents is quite distinct from the settings of previous case-control studies.

Infections in early life and childhood leukaemia risk: a UK case–control study of general practitioner records

“…Other recent studies have ascertained infections primarily from parental recall. The majority of these studies have observed slight inverse associations between infections or specific types of infections in early life and leukaemia risk (Neglia et al, 2000;Perrillat et al, 2002;Jourdan-Da Silva et al, 2004;Ma et al, 2005), but some studies have demonstrated little evidence of an association (Schuz et al, 1999;Macarthur et al, 2008), whereas others have shown an increased risk of leukaemia after infection (Dockerty et al, 1999;Chan et al, 2002). However, parental recall of infections is open to disease-dependent recall bias and has been shown to be an unreliable measure of both the timing and occurrence of infections (McKinney et al, 1991).…”

“…However, only one study has previously reported on ALL in relation to routinely recorded infections in early life . Other investigations of leukaemia and infections in early life (Dockerty et al, 1999;Chan et al, 2002;Perrillat et al, 2002;Jourdan-Da Silva et al, 2004;Ma et al, 2005;Macarthur et al, 2008) have primarily ascertained infection from parental recall, but this has been reported to be an inaccurate method for collecting data on childhood infections (McKinney et al, 1991). Furthermore, the parental recall of infections is open to disease-dependent bias as demonstrated by a recent study, which observed that the degree of underreporting of infections that were recorded in GP records differed in parents of children with leukaemia compared to parents of healthy children .…”

Biological diversity variations of pediatric acute leukemia in Brazil: contribution of immunophenotypic profiles to epidemiological studies

“…[9][10][11] Greaves' hypothesized that the risks of childhood c-ALL are increased by an immune proliferative stress and this hypothesis was supported by different epidemiological studies with indications that the timing of exposure to common infections would be a major determinant to leukemogenesis process. 12,13 A review of literature demonstrated that very few data are available regarding descriptive epidemiology and biological markers of childhood leukemia in South America. However, the more recent improvement of diagnostic techniques, including immunophenotyping and molecular biology, to assist in the Brazilian groups for ALL therapeutic trials have provided complete information regarding biological characteristics of leukemia subtypes in Brazil.…”

Infection During the First Year of Life and Acute Leukemia: Epidemiological Evidence

“…These indicators are designated as "proxies" and include socioeconomic status, surgical history, allergic diseases, immunizations, attendance at daycare, breastfeeding, neonatal infections, and prenatal history, among others. [14][15][16][17][18][19][20][21][22][23][24][25] …”

“…In a study similar to that of Chan et al, Roman et al found that exposure to fungal infections during the first year of life increases the risk of developing acute leukemia, with an OR of 1.4 (95% CI: 1.0-1.9). [14,85] …”