To determine whether neonatal phototherapy is associated with cancer in the first year after birth.
We analyzed a data set from the California Office of Statewide Health Planning and Development that was created by linking birth certificates, death certificates, and hospital discharge abstracts up to age 1 year. Subjects were 5 144 849 infants born in California hospitals at ≥35 weeks’ gestation from 1998 to 2007. We used International Classification of Diseases, Ninth Revision codes to identify phototherapy at <15 days and discharge diagnoses of cancer at 61 to 365 days. We adjusted for potential confounding variables by using traditional and propensity-adjusted logistic regression models.
Cancer was diagnosed in 58/178 017 infants with diagnosis codes for phototherapy and 1042/4 966 832 infants without such codes (32.6/100 000 vs 21.0/100 000; relative risk 1.6; 95% confidence interval [CI], 1.2–2.0, P = .002). In propensity-adjusted analyses, associations were seen between phototherapy and overall cancer (adjusted odds ratio [aOR] 1.4; 95% CI, 1.1–1.9), myeloid leukemia (aOR 2.6; 95% CI, 1.3–5.0), and kidney cancer (aOR 2.5; 95% CI, 1.2–5.1). The marginal propensity-adjusted absolute risk increase for cancer after phototherapy in the total population was 9.4/100 000 (number needed to harm of 10 638). Because of the higher baseline risk of cancer in infants with Down syndrome, the number needed to harm was 1285.
Phototherapy may slightly increase the risk of cancer in infancy, although the absolute risk increase is small. This risk should be considered when making phototherapy treatment decisions, especially for infants with bilirubin levels below current treatment guidelines.
We read with interest the really state of the art paper written by Wickremasinghe et al.1. It is wellknown that maunting evidence suggests the role of oxidative stress (OS) in ageing and carcinogenesis. Although several attempts have been made to survey the role of bilirubin and phototherapy in the oxidative/antioxidant balance, currently none has reached a definitive conclusion as to whether bilirubin has an antioxidant capacity or causes oxidative stress leading to encephalopathy or, together with photoherapy, infantile cancer 2.
We would like to elucidate better these phenomenons in this commentary with subheading: Neurodegeneration and Carcinogenesis: a return to immaturity? The neonatal brain, with its high concentrations of unsaturated fatty acids, high rate of oxygen consumption, low concentrations of antioxidants, and availability of redox-active iron and copper, is particularly vulnerable to OS. Morover, the copper metabolism in Wilson's disease and in the newborn infants is also similar. Both have large quantities of copper in the liver and in the brain (mainly in the basal ganglia) which is contrasted by an unusually low ceruloplasmin level in the blood 3. In addition, reactive oxygen species (ROS) contributes to increased blood-brain-barrier (BBB) permeability. Consequently, the immature and strikingly vulnerable neurons play important role in the pathogenesis of chronic bilirubin encephalopathy. According to our concept: BIND is a neurodegenerative disorder of immature brain caused by accumulation of free metals and unconjugated bilirubin-copper (UCB-Cu) complex (as prooxidant) in the basal ganglia and other parts of central nervous system (CNS) relevant to BIND. The main comorbidity is the hemolysis of neonatal blood red cells. During this process a great amount of heavy metals (mainly iron and copper) and Cu-UCB complex may circulate in the bloodstream. They can pass through the immature BBB with ROS-induced increased permeability, and finding entrance into the CNS . The copper atoms loosely bound to albumin in high concentration, and can be very easily taken out
by UCB 4. Free or loosely bound, redoxactive transition metal ions are potentially extremely pro-oxidant. In strictly biological terms the two most important such metals are iron and copper. In a book just published we have discussed the potential neuroprotective effects of
D-Penicillamine (D-PA) in BIND and ROP 5. We hope that our concept will help answer some of the unsolved questions and concerns ocurred in the etiology and pathomechanisms of BIND and the oxidative/antioxidant effects of UCB. It would be also important to determine whether phototherapy + D-PA how to influence the development of the early childhood cancer?
References
1. Wickremasinghe AC, Kuzniewicz MW, Barbara A., et al. Neonatal
Phototherapy and Infantile Cancer.
Pediatrics. 2016;137(6):e20151353
2. Liao S-L, The Role of Bilirubin and Phototherapy in the
Oxidative/Antioxidant Balance.
Pediatrics & Neonatology 2015; 56(2): 77–78
3. Chowrimootoo GFE, Scowcroft H, Seymour CA,
Caeruloplasmin isoforms in Wilson’s disease in neonates.
Arch Dis Child 1998;79(3): F198–F201
4. Adhikari S, Joshi R, Gopinathan C, Bilirubin as an antiprecipitant
against copper mediated denaturation of bovine serum albumin:
formation of copper–bilirubin complex.
Biochim. Biophys. Acta 1998;1380(1): 109-114.
5. Lakatos L., Balla G, D-Penicillamine in the neonatal period.
Chelation as neuroprotectant in the neonatal period.
LAP LAMBERT Publishing. 2016. ISBN-13: 978-3-659-86459-9
https://www.lap-publishing.com/