Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium

Abstract

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81‐0.96) or 7 to 12 months (OR 0.85, 0.79‐0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71‐0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63‐0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53‐0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B‐ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium

“…We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI) for each birth defect-leukemia combination, while adjusting for the following variables: study site, sex, birthweight (<2500; 2500-3999; >3999 g), gestational age (preterm [<37 weeks]; term [≥37 weeks]), maternal age (<25; 25-29; 30-34; 35-39; ≥40 years), birth year and child's ethnicity (non-Hispanic White; non-Hispanic Black; Hispanic; and other -these categories varied by study and were harmonized based on previous CLIC assessments). 29,30,36 These variables were selected based on previous assessments and to be consistent with other studies evaluating associations between nonchromosomal birth defects and pediatric cancer. 10,[26][27][28][29][30][31] Additionally, the categorical variables were designed similarly to what was used in previous CLIC assessments.…”

Associations between early‐life and in utero infections and cytomegalovirus‐positive acute lymphoblastic leukemia in children

“…2 It is theorized that a dysregulated immune response to childhood infections can provide the opportunity for pre-leukemic clones present at birth to expand, acquire new mutations and proliferate into overt leukemia. [8][9][10][11][12][13][14] Cytomegalovirus (CMV) infection early in life is associated with increased risk of ALL development in childhood. 4,5 CMV is a herpesvirus common in the general population that after acute infection survives in a latent state in a host.…”

“…One hypothesis to explain these seemingly contradictory associations is that children in daycare are exposed to antigens early and often in childhood and thereby develop a more competent immune response; whereas those who do not attend daycare subsequently have delayed infection exposures and in the absence of a well‐primed immune system experience a dysregulated immune response thereby increasing their risk of ALL 2 . It is theorized that a dysregulated immune response to childhood infections can provide the opportunity for pre‐leukemic clones present at birth to expand, acquire new mutations and proliferate into overt leukemia 8‐14 …”

“… 2 It is theorized that a dysregulated immune response to childhood infections can provide the opportunity for pre‐leukemic clones present at birth to expand, acquire new mutations and proliferate into overt leukemia. 8 , 9 , 10 , 11 , 12 , 13 , 14 …”

“… 4 , 5 CMV is a herpesvirus common in the general population that after acute infection survives in a latent state in a host. To achieve this, CMV interacts with the host immune system thereby altering its response to infection, 14 , 15 , 16 and individuals with latent CMV have also been shown to have aberrant immune responses to other antigens into adulthood. 17 , 18 , 19 , 20 , 21 In prior studies, we found that approximately half of ALL cases have CMV DNA present in the bone marrow at diagnosis further suggesting that CMV could contribute to ALL development.…”