Related Experiment Video
Updated: May 15, 2026
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective
Chris R Kelsey1, Isabel L Jackson, Scott Langdon
1Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. kelse003@mc.duke.edu
Background:
The primary objective of this study was to evaluate the association between radiation sensitivity of the lungs and candidate single nucleotide polymorphisms (SNP) in genes implicated in radiation-induced toxicity.
Methods:
Patients with lung cancer who received radiation therapy (RT) had pre-RT and serial post-RT single photon emission computed tomography (SPECT) lung perfusion scans. RT-induced changes in regional perfusion were related to regional dose, which generated patient-specific dose-response curves (DRC). The slope of the DRC is independent of total dose and the irradiated volume, and is taken as a reflection of the patient's inherent sensitivity to RT. DNA was extracted from blood samples obtained at baseline. SNPs were determined by using a combination of high-resolution melting, TaqMan assays, and direct sequencing. Genotypes from 33 SNPs in 22 genes were compared against the slope of the DRC by using the Kruskal-Wallis test for ordered alternatives.
Results:
Thirty-nine self-reported Caucasian patients with pre-RT and ≥6 month post-RT SPECTs, and blood samples were identified. An association between genotype and increasing slope of the DRC was noted in G(1301) A in XRCC1 (rs25487) (P = .01) and G(3748) A in BRCA1 (rs16942) (P = .03).
Conclusions:
By using an objective radiologic assessment, polymorphisms within genes involved in repair of DNA damage (XRCC1 and BRCA1) were associated with radiation sensitivity of the lungs.
