Influence of multiple genetic polymorphisms on genitourinary morbidity after carbon ion radiotherapy for prostate cancer.
OBJECTIVE
To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients.


METHODS
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 (2:1) 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.
Suga
Tomo
T
RadGenomics Research Group, National Institute of Radiological Sciences, Chiba, Japan.
Iwakawa
Mayumi
M
Tsuji
Hiroshi
H
Ishikawa
Hitoshi
H
Oda
Eisei
E
Noda
Shuhei
S
Otsuka
Yoshimi
Y
Ishikawa
Atsuko
A
Ishikawa
Ken-Ichi
K
Shimazaki
Jun
J
Mizoe
Jun-Etsu
JE
Tsujii
Hirohiko
H
Imai
Takashi
T
D000951:Antigens, Neoplasm / Q000235:genetics; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D008297:Male; D052801:Male Urogenital Diseases / Q000453:epidemiology / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D017411:Ribonucleoproteins, Small Nuclear; C431323:SART1 protein, human; C452858:XRCC8 protein, human; C075640:ID3 protein, human; D017430:Prostate-Specific Antigen