Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoin.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Kelsey, CR; Jackson, IL; Langdon, S; Owzar, K; Hubbs, J; Vujaskovic, Z; Das, S; Marks, LB
Published Date
- May 2013
Published In
Volume / Issue
- 14 / 3
Start / End Page
- 267 - 274
PubMed ID
- 23313170
Pubmed Central ID
- PMC3643296
Electronic International Standard Serial Number (EISSN)
- 1938-0690
Digital Object Identifier (DOI)
- 10.1016/j.cllc.2012.10.006
Language
- eng
Conference Location
- United States