Association between haplotypes of radiosensitive genes and the risk for adverse skin reactions following radiotherapy in breast cancer patients

Abstract

Purpose: To identify haplotypes that associated with the risk of adverse skin reactions following radiotherapy in a Japanese breast cancer population, we conducted a case-control association analysis and haplotype inference using unphased genotype data. Methods: Using DNA samples collected from 184 Japanese breast cancer patients who qualified for breast-conserving surgery and radiotherapy, we genotyped 905 SNPs from 127 candidate genes for radiation susceptibility. The adverse skin reactions were clinically graded according to the National Cancer Institute Common Toxicity Criteria. We first conducted a case-control analysis exploring the associations between all SNPs and adverse skin reactions by using logistic regression analysis. Second, Linkage disequilibrium mapping and haplotype-tagging SNPs selection were performed. Finally, haplotype frequencies of each selected locus were inferred. Genetic effects of the inferred haplotypes were analyzed in the same statistical way for the SNPs. Results: Twelve candidate loci involving 24 SNPs showed statistically significant association with the risk of adverse skin reactions. Six of 12 loci generated 42 haplotypes and 4 haplotypes of them associated with the risk of adverse skin reactions. This haplotype-based association analysis revealed that there were the adverse skin reaction-risk or -protective haplotypes. Conclusion: These findings suggested that genetic background is one of the factors that associated with the risk for adverse skin reactions following radiotherapy.