title: Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoin.
abstract: 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.
authors: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. kelse003@mc.duke.edu
authors: Chris R
authors: CR
authors: Kelsey
authors: Isabel L
authors: IL
authors: Jackson
authors: Scott
authors: S
authors: Langdon
authors: Kouros
authors: K
authors: Owzar
authors: Jessica
authors: J
authors: Hubbs
authors: Zeljko
authors: Z
authors: Vujaskovic
authors: Shiva
authors: S
authors: Das
authors: Lawrence B
authors: LB
authors: Marks
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015899:Tomography, Emission-Computed, Single-Photon; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human