Positive effect of single nucleotide RAD51 135G>C polymorphism and low Ku70 protein expression on female rectal cancer patients survival after preoperative radiotherapy.

BACKGROUND/AIMS: This is a retrospective analysis of 103 patients having locally advanced rectal cancer who received short-course radiotherapy (SCRT). The objective of the study was to check whether a polymorphism in the RAD51 gene (135 G>C), Ku70 protein expression, and tumor microenvironment: proliferation rate measured by BrdUrdLI and Ki-67LI, hypoxia (glucose transporter-1 expression), P53 protein expression, and DNA ploidy can influence DNA repair capacity, the factors contributing to patient overall survival (OS) and the incidence of recurrences and metastases.

MATERIALS AND METHODS: RAD51 (135 G>C) polymorphism was evaluated using restriction fragment length polymorphism polymerase chain reaction, and proteins were identified using immunohistochemistry.

RESULTS: There were 3 (2.9%) tumors with RAD51 CC, 75 (72.8%) with GG, and 25 (24.3%) with GC genotypes. The median follow-up time was 63.1 months (range 2-120). Patients with CC genotype survived significantly longer than those with GG and GC genotypes and did not develop any recurrences or distant metastases. Female patients with Ku70 expression (≤75.1) or RAD51CC genotype (impaired DNA damage repair and radiosensitive) had significantly longer OS (p=0.013) than those with Ku70>75.1 % or RAD51GG,GC (radioresistant phenotype) and male patients in the log-rank test. In multivariate analysis, positive prognostic factors for OS in the male patients were grade=1 and ≤17 days break in the treatment, whereas in the female subgroup, only radiosensitive phenotype (Ku70 ≤75.1% or RAD51CC genotype).

CONCLUSION: To the best of our knowledge, this is the first study to provide evidence for the positive effect of CC genotype of RAD51 or low Ku70 expression on OS in females with rectal cancer after SCRT.