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.

Figure 1

Boxplots for rs25487 (XRCC1) and rs16942 (BRCA1), Produced by Using the R Boxplot Function With Its Default Settings, Comparing Genotype With Slope of the Single Photon Emission Computed Tomography Dose-Response Curve. The Line in the Middle Is the Median (Q2). The Upper and Lower Edges of the Box Are the 25th (Q1) and 75th (Q3) Percentiles. The Height of the Box is the Interquartile Range (IQR). The Whiskers Are Computed as Follows: Exclude All Data Points That Are Either 1.5 × IQR Below Q1 or 1.5 × IQR Above Q3. The Whiskers Correspond to the Range of This Reduced Data Set. Any Data Points (outliers) From the Original Sample Below or Above the Whiskers Are Also Plotted