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A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint.

Publication ,  Journal Article
Kelsey, CR; Jackson, L; Langdon, S; Owzar, K; Hubbs, J; Vujaskovic, Z; Das, S; Marks, LB
Published in: Int J Radiat Oncol Biol Phys
February 1, 2012

PURPOSE: To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 (TGFβ1) gene are associated with radiation sensitivity using an objective radiologic endpoint. METHODS AND MATERIALS: Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGFβ1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose-response curve, reflecting the patient's inherent sensitivity to radiation therapy. Six TGFβ1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose-response curve, and genotype and TGFβ1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. RESULTS: 39 white patients with preradiation therapy and ≥ 6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose-response curve was associated with the C(-509)T SNP (p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGFβ1 ratios. CONCLUSIONS: This study suggests that a polymorphism within the promoter of the TGFβ1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).

Duke Scholars

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

February 1, 2012

Volume

82

Issue

2

Start / End Page

e247 / e255

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Tomography, Emission-Computed, Single-Photon
  • Statistics, Nonparametric
  • Sequence Analysis, DNA
  • Radiotherapy Dosage
  • Radiation Tolerance
  • Radiation Injuries
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
 

Citation

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MLA
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Kelsey, C. R., Jackson, L., Langdon, S., Owzar, K., Hubbs, J., Vujaskovic, Z., … Marks, L. B. (2012). A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint. Int J Radiat Oncol Biol Phys, 82(2), e247–e255. https://doi.org/10.1016/j.ijrobp.2011.02.064
Kelsey, Chris R., Lauren Jackson, Scott Langdon, Kouros Owzar, Jessica Hubbs, Zeljko Vujaskovic, Shiva Das, and Lawrence B. Marks. “A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint.Int J Radiat Oncol Biol Phys 82, no. 2 (February 1, 2012): e247–55. https://doi.org/10.1016/j.ijrobp.2011.02.064.
Kelsey CR, Jackson L, Langdon S, Owzar K, Hubbs J, Vujaskovic Z, et al. A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):e247–55.
Kelsey, Chris R., et al. “A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint.Int J Radiat Oncol Biol Phys, vol. 82, no. 2, Feb. 2012, pp. e247–55. Pubmed, doi:10.1016/j.ijrobp.2011.02.064.
Kelsey CR, Jackson L, Langdon S, Owzar K, Hubbs J, Vujaskovic Z, Das S, Marks LB. A polymorphism within the promoter of the TGFβ1 gene is associated with radiation sensitivity using an objective radiologic endpoint. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):e247–e255.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

February 1, 2012

Volume

82

Issue

2

Start / End Page

e247 / e255

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta1
  • Tomography, Emission-Computed, Single-Photon
  • Statistics, Nonparametric
  • Sequence Analysis, DNA
  • Radiotherapy Dosage
  • Radiation Tolerance
  • Radiation Injuries
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis