Childhood Cancer: Radiation Susceptibility & Lifelong Risk of Following Second Primary Tumors

Risk factors for most childhood cancers remain largely unknown. An established, but rare environmental risk factor for acute myeloid leukemia in childhood and second primary neoplasms is an exposure to high doses of ionizing radiation, either due to nuclear disasters or in cancer therapies. However, only 8% of childhood cancer survivors develop second primary neoplasms within 30 years. The magnitude of the risk of first primary childhood neoplasms from very low-doses is still uncertain and difficult to resolve via conventional epidemiological studies. Low doses of ionizing radiation are commonly used in medical diagnostics, such as computed tomography. They also appear in addition to applied high doses of ionizing radiation during radiotherapy as unwanted exposure outside the primary radiation beam and are also considered as a risk factor. Indeed, genomic variants that affect the cellular radiation-response are assumed to be involved in the etiology of childhood cancer and second primary neoplasms as well. However, known genetic susceptibility with low risk and rare genetic disorders with high risk explain less than 10% of childhood cancer cases today.

To this day, information on genetic drivers affecting pediatric oncogenesis, radiation-response, radiotherapy-associated second primary neoplasms, and the interplay of these mechanisms is scarce. Cancer survivors suffer a lifelong burden of different late toxicities, with second primary neoplasms being an especially grave occurrence. Compared to adults, children are at higher risk for developing second primary neoplasms as result of radiation therapies, due to an increased sensitivity of their young, developing bodies to radiation therapy and higher life-expectancies post-treatment. As high-throughput sequencing methods and new technologies became broadly available, for example analyses of single nucleotide polymorphisms, gene expression, epigenetic modifications, and metabolomics should be used for comprehensive examination in the area of radiation susceptibility, childhood and second primary cancer. Methodological, original and review articles that seek to better characterize the effects of radiation susceptibility on risk of childhood cancer and/or the lifelong risk of following second primary cancers are welcomed as contributions to the topic.

The scope of this Research Topic is to increase knowledge on genetic factors of pediatric oncogenesis, their interplay with modifiable radiation exposures and late effects, such as second primary cancers to achieve progress in radiation-related childhood cancer prevention, therapy, and care.

Articles should focus on, but are not limited to, the following topics:

1. Strategies to identify germline predispositions related to response to low and/or high doses of ionizing radiation, childhood and/or second primary cancers
2. Identification and characterization of biomarkers to predict the response and prognosis of radiation therapy in childhood cancer patients
3. Development of new research concepts to identify radiation susceptibility in childhood cancer patients
4. Advances in understanding of the molecular response and mechanisms after exposure to ionizing radiation in human bodies

Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in Frontiers in Oncology.