The association between atopy and childhood/adolescent leukemia: a meta-analysis

Abstract

Atopic disease is hypothesized to be protective against several malignancies, including childhood/adolescent leukemia. To summarize the available epidemiologic evidence, the authors performed a meta-analysis of associations between atopy/allergies, asthma, eczema, hay fever, and hives and childhood/adolescent leukemia, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). They searched MEDLINE literature (1952-March 2009) and queried international experts to identify eligible studies. Ten case-control studies were included. Summary odds ratios and 95% confidence intervals were computed via random-effects models. Odds ratios for atopy/allergies were 1.42 (95% confidence interval (CI): 0.60, 3.35) for 3 studies of leukemia overall, 0.69 (95% CI: 0.54, 0.89) for 6 studies of ALL, and 0.87 (95% CI: 0.62, 1.22) for 2 studies of AML, with high levels of heterogeneity detected for leukemia overall and ALL. Inverse associations were observed for ALL and asthma (odds ratio (OR) = 0.79, 95% CI: 0.61, 1.02), eczema (OR = 0.74, 95% CI: 0.58, 0.96), and hay fever (OR = 0.55, 95% CI: 0.46, 0.66) examined separately. Odds ratios for ALL differed by study design, exposure data source, and latency period, indicating that these factors affect study results. These results should be interpreted cautiously given the modest number of studies, substantial heterogeneity, and potential exposure misclassification but are useful in designing future research.

Figure 1.

Search strategy and study selection process used in a meta-analysis of the association between atopy and leukemia, 1952–March 2009. QOL, quality of life.

Figure 2.

Study-specific and random-effects summary odds ratios (ORs) for the associations between leukemia overall, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) and A) atopy or allergies, B) asthma, C) eczema, D) hay fever, and E) hives. The size of each box indicates the relative weight of each study in the meta-analysis; the bars show the 95% confidence intervals (CIs). Higgins’ I² statistic and 95% CI, a measure of the degree of heterogeneity across studies, is also shown for each summary OR. The 95% CI could not be calculated for I² with fewer than 2 df. For Fraumeni et al. (19), the crude OR was calculated from data provided in the published article. For Bross and Natarajan (20), the age-adjusted OR was calculated from data provided in the paper by Smith et al. (55). For Söderberg et al. (14), results for children/adolescents under age 19 years were obtained from the first author (Karin Söderberg, Karolinska Institutet, personal communication, 2009).

Figure 2.

Study-specific and random-effects summary odds ratios (ORs) for the associations between leukemia overall, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) and A) atopy or allergies, B) asthma, C) eczema, D) hay fever, and E) hives. The size of each box indicates the relative weight of each study in the meta-analysis; the bars show the 95% confidence intervals (CIs). Higgins’ I² statistic and 95% CI, a measure of the degree of heterogeneity across studies, is also shown for each summary OR. The 95% CI could not be calculated for I² with fewer than 2 df. For Fraumeni et al. (19), the crude OR was calculated from data provided in the published article. For Bross and Natarajan (20), the age-adjusted OR was calculated from data provided in the paper by Smith et al. (55). For Söderberg et al. (14), results for children/adolescents under age 19 years were obtained from the first author (Karin Söderberg, Karolinska Institutet, personal communication, 2009).

Figure 2.

Study-specific and random-effects summary odds ratios (ORs) for the associations between leukemia overall, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) and A) atopy or allergies, B) asthma, C) eczema, D) hay fever, and E) hives. The size of each box indicates the relative weight of each study in the meta-analysis; the bars show the 95% confidence intervals (CIs). Higgins’ I² statistic and 95% CI, a measure of the degree of heterogeneity across studies, is also shown for each summary OR. The 95% CI could not be calculated for I² with fewer than 2 df. For Fraumeni et al. (19), the crude OR was calculated from data provided in the published article. For Bross and Natarajan (20), the age-adjusted OR was calculated from data provided in the paper by Smith et al. (55). For Söderberg et al. (14), results for children/adolescents under age 19 years were obtained from the first author (Karin Söderberg, Karolinska Institutet, personal communication, 2009).

Figure 3.

Random-effects summary odds ratios (ORs) for the association between acute lymphoblastic leukemia and A) atopy or allergies, B) asthma, and C) eczema, according to factors related to study quality. The control response rate was not available for 1 study (13). Bars, 95% confidence interval (CI). SES, socioeconomic status.

Figure 3.

Random-effects summary odds ratios (ORs) for the association between acute lymphoblastic leukemia and A) atopy or allergies, B) asthma, and C) eczema, according to factors related to study quality. The control response rate was not available for 1 study (13). Bars, 95% confidence interval (CI). SES, socioeconomic status.

Figure 3.

Random-effects summary odds ratios (ORs) for the association between acute lymphoblastic leukemia and A) atopy or allergies, B) asthma, and C) eczema, according to factors related to study quality. The control response rate was not available for 1 study (13). Bars, 95% confidence interval (CI). SES, socioeconomic status.