Abstract 4348: Changes in leukocyte gene expression after computer tomography in children

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Objective: Computer tomography (CT) involves ionizing X-irradiation which can lead to DNA damage from free radicals. CT use has risen dramatically due to its high speed and diagnostic value but it leads to an estimated lifetime cancer risk of up to 4%, with highest risk for children. We tested in a pilot project whether expression of genes hypothesized to change upon ionizing radiation are altered in the leukocytes of young children undergoing CT exams that involved relatively low X-ray doses. Methods: 17 children aged 0.25-6 years and scheduled for medically indicated CT donated blood immediately before and 1 hour after a CT exam (median 340.9 mGy*cm equivalent to 2.3 mSv). Blood was collected into PaxGene tubes and RNA was extracted according to the suggested protocol, labeled and hybridized onto Affymetrix Gene 1.0 ST Arrays. Preliminary expression analysis was done on 24 genes suggested to fluctuate after ionizing radiation: GADD45, CDKN1A, ATM, ERP29, TP53, CDKN2A, MUC1, CDH6, DDB2, XPC, TNFRSF10B, FHL2, CCNG1, PCNA, CCNB1, MDM2, BAX, MAPK8, ALB, PPP1R14A, FLT3LG, HP, RPA2, NFKB1. Significance was determined by paired t-tests and stepwise multiple regression using the SAS 9.2 software. Results: In post versus pre CT leukocytes paired t-tests revealed that the expression of ERP29 decreased (p=0.002) but that the expression of the other 23 genes did not change significantly except for possible suggestive increases of XPC (p=0.11) and MUC1 (p=0.18) and decreases of PCNA (p=0.16) and PPP1R14A (p=0.16) expression. Stepwise multiple regression tests for predictors of pre to post changes revealed (i) that the CT dose (mGy*cm) was positively associated with PCNA expression (p=0.001), (ii) that the effective dose (mSv) was positively associated with TP53 (p=0.02) and FLT3LG (p=0.02) expression, and (iii) that the radiation history was associated with increased MDM2 (p=0.002) but negatively associated with PPP1R14A (p=0.05) and FLT3LG (p=0.03) expression. Stepwise multiple regression tests for predictors of baseline levels showed that the radiation history was associated with higher baseline expression of XPC (p=0.05), MDM2 (p=0.01), and BAX (p=0.001) but lower baseline expression of ALB (p=0.04). Conclusions: Few of the investigated 24 radiosensitive genes with the exception of ERP29 changed expression levels in the leukocytes of the 17 young children studied after these subjects received relatively low radiation doses. However, radiation dose dependent changes after CT were observed (PCNA, TP53, and FLT3LG expression). In addition, radiation history was found to be positively associated with baseline expression levels of XPC, MDM2, and BAX, but negatively with that of ALB. Genome wide analyses are currently under way to explore expression changes of other genes in these 17 subjects. Larger studies are needed to confirm these preliminary findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4348. doi:1538-7445.AM2012-4348