Single Nucleotide Polymorphisms Associated with Risk of Adverse Skin Reactions to Radiation in Patients Undergoing Breast-conserving Therapy: Single-institution Analysis

Purpose/Objective(s)In a previous study involving 9 institutions, 8 single nucleotide polymorphism (SNP) markers in 6 loci of genome were found to be associated with risks of early adverse skin reaction to radiation following breast-conserving surgery. In the present study, the SNPs for these loci were reanalyzed in patients, including new cases, treated and followed at a single institution with a uniform policy, in order to confirm the significance of previously reported polymorphisms. Association with adverse skin reaction within 6 months after radiation was also analyzed. An area under a receiver operating characteristic curve (AUC-ROC) analysis was newly applied in this study.\nMaterials/MethodsWith informed consent, DNA samples from 115 patients undergoing prophylactic radiation after breast-conserving surgery were obtained for SNP analysis. All patients received 50 Gy in 2-Gy daily fractions by tangential irradiation with or without an electron boost of 10 Gy in 5 fractions. Using the National Cancer Institute-Common Toxicity Criteria scoring system version 2, the patients were grouped according to adverse skin reactions within 3 months after starting radiotherapy (grade ≤ 1, n = 74; grade = 2, n = 41) as well as those within 6 months (grade 0, n = 61; grade 1, n = 52). Eight SNPs from the 6 loci were analyzed for assessment of associations between groups. A risk score of a patient was calculated according to a total number of risk genotype(s) (an increased risk genotype = 1 and a reduced risk genotype = -1). The sensitivity and specificity of the markers were evaluated using an AUC-ROC analysis.\nResultsEach genotype of the PTTG1 rs3811999 CC, the RAD9A rs917570 CC, and the RAD9A rs2286620 TT showed association with an increased risk (P = 0.024, 0.040, and 0.017, respectively), while the REV3L rs190246 GG/GT and rs240962 GG/GT genotypes were associated with a reduced risk of adverse skin reaction within 3 months (P = 0.0059 and 0.049, respectively). After applying Bonferroni correction, only the rs190246 GG/GT genotype was considered to remain statistically significant (Pcorrected = 0.047). When combined effects of the 3 increased-risk genotypes and the 2 reduced-risk genotypes were examined by the AUC-ROC method, the AUC value of the model reached 0.72. No association was observed between the analyzed SNPs and adverse skin reaction within 6 months.\nConclusionsThis single-institution analysis confirmed the significance of combined effects of the SNPs on PTTG1, RAD9A, and REV3L genes in determining early adverse skin reaction. These SNPs were, however, not associated with reaction within 6 months, suggesting that they are not related to recovery of skin damage between 3 and 6 months after radiation