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Phototherapy And Increased Cancer Risk in Neonates

In neonates, phototherapy is commonly used to treat hyperbilirubinemia, but it is thought to increase the risk of cancer. In adults and children, phototherapy can be used in the treatment of psoriasis, atopic dermatitis, and acne.

Phototherapy And Increased Cancer Risk
A Neonate gets Phototherapy

Association of Phototherapy in Neonates with Cancer Risks

Blue light phototherapy with peak emission 450 nm, has been used for decades to treat hyperbilirubinemia neonates. The 380-550 nm spectrum of blue light contains most of the visible light at 450 nm and a small amount of ultraviolet light (0.3%). The action mechanism of phototherapy is converting bilirubin into less lipophilic and water-soluble isomers so that it can be excreted more easily in urine and bile.

Blue light is thought to increase cancer risk because it is toxic to epithelial cells by inducing the production of free radicals and damage to mitochondria and DNA. Studies report that phototherapy has the potential to increase the incidence of cancer because blue light is mutagenic in vitro. In vivo studies in human infants have shown DNA damage, changes in cytokine levels and oxidative stress after phototherapy. All of these changes are related to cancer pathomechanism.

A cohort study in the United Kingdom, involving more than 77 thousand samples, tried to assess whether exposure to blue light in neonates increases the risk of skin cancer. The study reported that only 2 melanoma events were found in the group exposed to blue light during neonates, compared to 16 cases in the unexposed group. No basal cell carcinoma or squamous cell carcinoma was found in either group. The study concluded that there was no significant difference in the risk of skin cancer between individuals exposed to phototherapy and those who did not.

Another study conducted by Wickremasinghe et al. tried to see whether phototherapy in the neonatal period would increase the risk of cancer in the first year of life. This study reported that phototherapy increases the risk of cancer as much as 1.4 times. Specifically, it reported that phototherapy increased the risk of myeloid leukemia 2.6 times and kidney cancer 2.5 times. The results of this study must be analyzed carefully because they still have some shortcomings, including controlling for confounding factors and no data regarding the duration and intensity of phototherapy.

Another retrospective cohort study reported similar results, that phototherapy increasing the risk of cancer. The study reported that there were 60 individuals diagnosed with cancer out of 39,403 individuals who were exposed to phototherapy during neonates or the equivalent of 25 per 100,000 person-years whereas there were 651 individuals diagnosed with cancer out of 460,218 individuals who were not exposed to phototherapy during neonates or the equivalent of 18 per 100,000 person-years. Statistical analysis shows an increase in the risk of cancer by 1.4 times. However, just like the Wickremasinghe et al. study, this study also did not control for confounding factors.
Association of Phototherapy in Children and Adults with the Risk of Forming Cancer

In children and adults, the use of ultraviolet light phototherapy to treat various skin disorders, such as psoriasis, atopic dermatitis, and acne. It is suspected that one of the long-term effects of ultraviolet light phototherapy is carcinogenesis. Ultraviolet light causes photodermatitis, which also results in DNA damage or mutations due to oncogenes activation and suppression of tumor suppressor genes.

A retrospective study assessed the risk of skin cancer in psoriasis patients treated with phototherapy Plus Ultraviolet A (PUVA) and narrowband Ultraviolet B (nb-UVB). Of the 92 study subjects studied, 42 patients received PUVA therapy, and 50 patients received nb-UVB. In the PUVA group, 4.7% of patients had skin cancer, where one person had melanoma, 7 had basal cell carcinoma, and 1 had squamous cell carcinoma. In the nb-UVB group, 12% had skin cancer, of which 2 had melanoma, 4 had basal cell carcinoma, and 8 had squamous cell carcinoma.

Another study, which was a systematic review in 2012, investigated the risk of cancer in psoriasis patients managed by PUVA and nb-UVB. The study results concluded that there was a significant increase in the risk of skin cancer in psoriasis patients treated with PUVA.

A study in Scotland with a larger sample size reported different results. This study investigated the risk of carcinogenesis in patients receiving nb-UVB phototherapy. That study concluded that there was no association between cancer risk and exposure to nb-UVB phototherapy.

Conclusion
Phototherapy is thought to increase the risk of cancer. In neonates, blue light phototherapy is often used for patients with neonatal jaundice. Blue light is thought to increase cancer risk because it is toxic to epithelial cells by inducing the production of free radicals and damage to mitochondria and DNA. In children and adults, phototherapy with ultraviolet light is used for the management of skin disorders, such as psoriasis and atopic dermatitis. Ultraviolet light causes photodermatitis, which also results in DNA damage or mutations due to oncogenes activation and suppression of tumor suppressor genes.

Cohort studies with large sample sizes in infants exposed to blue light found no increased risk of skin cancer. While studies with a smaller number of subjects showed an increase, but these studies did not control for confounding factors, so blue light therapy in neonates is probably quite safe.

Studies also showed an increased risk of cancer in phototherapy with PUVA, but further research is still needed in this regard. Phototherapy with nb-UVB does not show an increased risk of cancer.


References
1. Chotikasemsri P, Tangtrakulwanich B, Sangkhatat S. The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin. In: BioMed Research International. 2017;7604861: 1-9. Available from: https://www.hindawi.com/journals/bmri/2017/7604861/
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6. Yurdakok M. Phototherapy in the Newborn: What’s New?. In: Journal of Pediatrics and Neonatal Individualized Medicine. 2015;4(2): e040255. Available from: http://www.jpnim.com/index.php/jpnim/article/view/040255/310
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9. Maiorino A, Simone CD, Perino F, Caldarola G, Peris K. Melanoma and Non-Melanoma Skin Cancer in Psoriatic Patients Treated with High Dose Phototherapy. In: Journal of Dermatological Treatment. 2016;27(5): 443-7. Available from: https://www.tandfonline.com/doi/full/10.3109/09546634.2015.1133882?scroll=top&needAccess=true
10. Archier E, Devaux S, Castela E, et al. Carcinogenic risks of Psoralen UV-A therapy and Narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. Journal of the European Academy of Dermatology and Venereology, 2012. 26: 22–31. doi:10.1111/j.1468-3083.2012.04520.x
11. Hearn RMR., Kerr AC, Rahim KF, Ferguson J, Dawe RS. Incidence of skin cancers in 3867 patients treated with narrow-band ultraviolet B phototherapy. British Journal of Dermatology, 2008. 159(4): 931–935. doi:10.1111/j.1365-2133.2008.08776.x

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