The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia.
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Embargo End Date
ICR Authors
Authors
Pombo-de-Oliveira, MS
EMiLI Study Group,
Petridou, ET
Karalexi, MA
Junqueira, MER
Braga, FHP
Bouzas, LF
Murra, GRC
Lopes, LF
Ntzani, E
Greaves, M
EMiLI Study Group,
Petridou, ET
Karalexi, MA
Junqueira, MER
Braga, FHP
Bouzas, LF
Murra, GRC
Lopes, LF
Ntzani, E
Greaves, M
Document Type
Journal Article
Date
2023-03-06
Date Accepted
2022-12-07
Abstract
BACKGROUND: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development. METHODS: Cases comprised 1,126 children (0-12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002-2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models. RESULTS: C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04-1.15; ORBCP-ALL: 1.09; 95% CI, 1.03-1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P < 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40-4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27-4.24; ORBCP-ALL: 2.37; 95% CI, 1.18-4.76). CONCLUSIONS: Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL. IMPACT: These findings encourage the exploration of potential preventive interventions. See related commentary by Wiemels and Gallant, p. 292.
Citation
Cancer Epidemiology, Biomarkers and Prevention, 2022, pp. EPI-22-0664 -
Source Title
Cancer Epidemiology, Biomarkers and Prevention
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1055-9965
eISSN
1538-7755
1538-7755
1538-7755
Collections
Research Team
Biol Childhood Leukaemia