Pediatric cancer risk factors: A review of literature

Abstract Introduction According to Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI), the incidence of all pediatric cancers in the United States has increased by approximately 0.73% annually over the past several decades. We set out to complete a systematic literature review to investigate potential risk factors that may explain the rising incidence of pediatric cancers in the United States, as reported by SEER and the Centers for Disease Control and Prevention. Methods We created a thorough search criterion and conducted a comprehensive review of 3,862 research and epidemiological studies, meta-analyses, and review articles published between January 2014 and March 2021. This literature focuses on childhood, pregnancy and birth-related, and environmental risk factors for pediatric cancers. These searches were performed using both Ovid MEDLINE and Scopus databases. For exposure sources included in this review, we considered both direct childhood exposures and parental exposures occurring prior to conception and during pregnancy, across all types of childhood cancer. Results The literature review identified statistically significant associations between various risk factors and pediatric cancer incidence. Confirmed risk factors include both established and emerging exposures such as genetic predisposition (50% of patients with Li-Fraumeni Syndrome develop early neoplasms), birth defects (trisomy-21 increases risk for cancer 20-500-fold), prior cancer or cancer treatment (increases cancer risk 4-6 fold), medical ionizing radiation (excess relative risk (ERR) pooled 26.9%; CI 2.7–57.1), ultraviolet light exposure, organ transplantation (33% of pediatric transplant patients develop cancer post-transplant), and multiple prenatal exposures (e.g., alcohol (OR 2.36; CI 1.60–3.49), cigarette smoking (OR 1.86; 95% CI 1.26–2.74), and coffee consumption during pregnancy (OR 1.72; CI: 1.37–2.16)). Additional maternal and perinatal factors associated with increased risk include maternal diabetes (OR 1.44; CI 1.27–1.64), preterm or post-term birth (OR 1.42; CI 1.21–1.67), low birth weight (OR 1.4; CI 1.0–2.0), diethylstilbestrol exposure (increases risk 40-fold), and advanced parental age (OR 1.08; CI 1.04–1.11). Environmental and occupational exposures linked to increased cancer risk include traffic-related air pollution (OR 1.53; CI 1.12-2.10), indoor paint (OR 1.54; CI 1.28-1.85), pesticides (RR 1.34; CI 1.15-1.56), and parental occupational exposure to benzene (RR 2.34; CI 1.72-3.18). Associations were also found with certain allergic conditions (OR 0.60; 95% CI 0.41–0.87), infections (OR 0.3; CI 0.2–0.7), breastfeeding status (OR 0.80; CI 0.72–0.90), childhood diet (OR 3.03; CI 1.37–6.71), and vaccination history (OR 0.18; CI 0.10–0.32). Several risk factors demonstrate mixed or inconclusive evidence with studies showing increased, decreased, or null associations. These included maternal obesity (mixed data), birth order (increased risk for first born, decreasing risk for subsequent siblings), multiple gestation (mixed results), mode of delivery (decreases risk for some cancers (aOR 0.67; CI 0.45–0.99) but increases risk for others (aOR 7.8; CI 2.18–28.03)), prenatal radiation exposure (OR 0.93; CI 0.68–1.28), radon (mixed results), proximity to nuclear plants (biologic feasibility but limited evidence), and low-to-medium electromagnetic field exposure (mixed results but difficult to adjust for confounding variables). Other exposures reviewed show limited or no statistical significance regarding childhood cancers. These included childhood medications (HR 2.9; CI 0.9–9.3), childhood body mass index (insufficient evidence), phototherapy (no increased risk with adjusted confounders), assisted reproductive therapies (no increased risk), and exposure to farm animals (insufficient evidence). Conclusions This comprehensive literature review identifies a substantial body of evidence linking both established and emerging risk factors to pediatric cancer incidence. While many well-recognized exposures continue to warrant prevention and mitigation, several lesser-known factors merit further investigation and potential public health action. The broad scope of this review underscores the depth of existing research; however, the short timeframe and exclusion of evidence outside this window, heterogeneity of study designs, and exposure classification and recall limit direct comparisons across all studies.