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.
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: L B Marks; M T Munley; D P Spencer; G W Sherouse; G C Bentel; J Hoppenworth; M Chew; R J Jaszczak; R E Coleman; L R Prosnitz Journal: Int J Radiat Oncol Biol Phys Date: 1997-05-01 Impact factor: 7.038
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Authors: Junan Zhang; Jinli Ma; Sumin Zhou; Jessica L Hubbs; Terence Z Wong; Rodney J Folz; Elizabeth S Evans; Ronald J Jaszczak; Robert Clough; Lawrence B Marks Journal: Int J Radiat Oncol Biol Phys Date: 2009-07-23 Impact factor: 7.038
Authors: Michelle A T Hildebrandt; Ritsuko Komaki; Zhongxing Liao; Jian Gu; Joe Y Chang; Yuanqing Ye; Charles Lu; David J Stewart; John D Minna; Jack A Roth; Scott M Lippman; James D Cox; Waun Ki Hong; Margaret R Spitz; Xifeng Wu Journal: PLoS One Date: 2010-08-25 Impact factor: 3.240
Authors: J Joshua Smith; Isaac Wasserman; Sarah A Milgrom; Oliver S Chow; Chin-Tung Chen; Sujata Patil; Karyn A Goodman; Julio Garcia-Aguilar Journal: Int J Radiat Oncol Biol Phys Date: 2016-12-18 Impact factor: 7.038