Objective: To detect K-ras mutations in rectal carcinoma before and after preoperative radiotherapy, and study genetics effect of radiotherapy in rectal cancer.
Methods: Forty patients with rectal cancer in pTNM stage II or III were enrolled. There were 20 males and 20 females. Sixteen tumours were pTNM II stage, 24 pTNM III. All patients received preoperative adjuvant radiotherapy. The treatment time is 4 weeks for 40 Gy in 2.0 Gy fractions and it is usually followed by an interval of 1-2 weeks before the operation. Tumor tissue and normal mucosa 2, 4, 6 cm to tumor were collected from patients before preoperative adjuvant radiotherapy and after operation. The K-ras mutations in codon 12 were investigated using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in tumors and normal mucosa.
Results: The frequencies of K-ras mutations before preoperative adjuvant radiotherapy in tumor tissue and normal mucosa 2, 4, 6 cm to tumor were 47.5%, 22.5%, 2.5% and 0. The frequencies of K-ras mutations before preoperative adjuvant radiotherapy were higher in tumor tissue than in normal mucosa, and were higher in normal mucosa 2 cm to tumor than 4 cm and 6 cm to tumor. The postoperative frequencies of K-ras mutations in tumor tissue and normal mucosa 2 cm, 4 cm, 6 cm to tumor were 25.0%, 5.0%, 0 and 0. Compared to same locations of control group, the frequency of K-ras mutations in tumor tissue and normal mucosa 2 cm to tumor significantly decreased after radiotherapy.
Conclusion: Frequency of K-ras mutations of rectal cancer issue and normal mucosa 2 cm to tumor were significantly higher than other normal rectal mucosa, and decreased significantly after radiotherapy. So radiotherapy can inhibit early events of carcinogenesis of mucosa nearby tumor. It was the potential reason of increased rates of resection and sphincter-saving after radiotherapy.