The present study aimed to explore the effects of pri-let-7a-1 rs10739971 and FAS-670 rs1800682 polymorphisms on the pathogenesis of radiation-induced intestinal toxicity in prostate cancer (PC) patients.

Material and methods:
Three hundred eighty PC patients with or without signs of intestinal toxicity were enrolled in a study on the effects of let-7a rs10739971 and FAS-670 rs1800682 polymorphisms on rectal volume and the risk of intestinal toxicity. In addition, real-time PCR, Western blot analysis, immunohistochemistry (IHC), luciferase assays and computational analyses were performed to explore the mechanism underlying the role of let-7a rs10739971 polymorphism in radiation-induced intestinal toxicity.

The let-7a rs10739971 polymorphism but not the FAS-670 rs1800682 polymorphism was closely associated with the risk of radiation-induced intestinal toxicity featured by a high rectal volume. In addition, there was no significant association between the rectal volume and the genotype and allele frequencies of FAS -670 rs1800682 and Pri-let-7a-1 rs10739971 polymorphisms. The GG genotype of let-7a rs10739971 polymorphism reduced let-7a expression but enhanced FAS expression. In addition, the intestinal toxicity (–) group showed a much higher level of let-7a and a much lower level of FAS than the intestinal toxicity (+) group. FAS was a virtual target gene of let-7a, which decreased FAS protein expression in a dose-dependent manner.

The GG genotype of pri-let-7a-1 rs10739971 polymorphism could increase the risk of radiation-induced intestinal toxicity in PC patients. Therefore, the pri-let-7a-1 rs10739971 polymorphism could be used as a putative marker to predict the risk of intestinal toxicity in PC patients undergoing radiotherapy.

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