Is There a Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review

Abstract

Childhood obesity is a growing epidemic with numerous global health implications. Over the past few years, novel insights have emerged about the contribution of adult obesity to cancer risk, but the evidence base is far more limited in children. While pediatric patients with acute lymphoblastic leukemia (ALL) are at risk of obesity, it is unclear if there are potential causal mechanisms by which obesity leads to ALL development. This review explores the endocrine, metabolic and immune dysregulation triggered by obesity and its potential role in pediatric ALL’s genesis. We describe possible mechanisms, including adipose tissue attraction and protection of lymphoblasts, and their impact on ALL chemotherapies’ pharmacokinetics. We also explore the potential contribution of cytokines, growth factors, natural killer cells and adipose stem cells to ALL initiation and propagation. While there are no current definite causal links between obesity and ALL, critical questions persist as to whether the adipose tissue microenvironment and endocrine actions can play a causal role in childhood ALL, and there is a need for more research to address these questions.

Maternal Body Mass Index, Diabetes, and Gestational Weight Gain and Risk for Pediatric Cancer in Offspring: A Systematic Review and Meta-Analysis

“…We found a statistically significant 7% increased risk of childhood leukemia for every 5-unit increase in prepregnancy BMI. Obesity has been repeatedly linked to leukemia risk in adult populations ( 65-67 ), but recent research has identified links between childhood obesity and childhood leukemia ( 68-71 ). Our own research has demonstrated a statistically significant association between childhood obesity and ALL risk among 4726 pediatric leukemia cases ( 71 ), suggesting early obesity exposure may propagate pediatric leukemia risk.…”

“…Our own research has demonstrated a statistically significant association between childhood obesity and ALL risk among 4726 pediatric leukemia cases ( 71 ), suggesting early obesity exposure may propagate pediatric leukemia risk. Obesity may specifically promote leukemogenesis via several mechanisms, including altered adipokine secretion ( 68 ), decreased circulating adiponectin ( 72 ), and increased leptin bioavailability ( 73 , 74 ). Additionally, as obesity heritability is estimated to be 0.85-0.9 ( 75 , 76 ), obese mothers are more likely to have obese children, thus increasing leukemogenesis risk; however, with our data, there was no way to determine leukemia risk attributable to obesity genomics.…”

Exploring the Impact of the Obesity Paradox on Lung Cancer and Other Malignancies

“…It is likely related to the fact that if a person is obese as a child, they also tend to be obese as an adult. Increased BMI as a teen was associated with a higher risk for leukemia (OR = 1.32, 95% CI 1.15-1.53) [51,52], Hodgkin's disease (HR = 1.25, 95% CI 1.13-1.37) [49,53], and colon cancer (39% increase in men and 19% increase in women) [54].…”

How Does Obesity Cause Cancer?

“…The articles accepted into this series focus on liver [ 4 , 5 , 6 ], uterine [ 7 ], skin [ 8 ], breast [ 9 , 10 , 11 ], prostate [ 12 ], colon [ 13 , 14 ], pancreatic [ 15 ], and acute lymphoblastic leukemia cancers [ 16 ], with a general overview of the potential impacts of obesity-related changes in host metabolism on cancer development and/or progression [ 17 ].…”

“…Excess body mass is linked to paediatric acute lymphoblastic leukemia (ALL), but little is known about the causal role of excess weight. In this edition, Dushnicky and colleagues review the potential effects of obesity on ALL risk in the context of endocrine, metabolic and immune dysregulation [ 16 ].…”