Influence of multiple genetic polymorphisms on genitourinary morbidity after carbon ion radiotherapy for prostate cancer.

ABSTRACT

PURPOSE: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients. METHODS AND MATERIALS A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (21) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher's exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers. RESULTS: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as "risk genotypes." Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes. CONCLUSIONS: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor.