Analysis of Single Nucleotide Polymorphisms and Radiation Sensitivity of the Lung Assessed With an Objective Radiologic Endpoin

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• 作者：Chris R. Kelsey¹ ; ^{kelse003@mc.duke.edu} ; Isabel L. Jackson² ; Scott Langdon³ ; Kouros Owzar⁴ ; Jessica Hubbs⁵ ; Zeljko Vujaskovic¹ ; Shiva Das¹ ; Lawrence B. Marks⁵
• 关键词：Genetics ; Lung toxicity ; Radiation sensitivity ; Single photon emission computed tomography ; Single-nucleotide polymorphism
• 刊名：Clinical Lung Cancer
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：14
• 期：3
• 页码：267-274
• 全文大小：368 K

文摘

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 ¡Ý6 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.