Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depending on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.

The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results indicate that the combined analysis of Apolipoprotein E, Factor X, and Pantothenate Kinase 4 allows discriminating between exposure to 2 Gy and lower and between 10 Gy and higher. The discrimination is possible up to 1 mo after exposure.