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The study describes a relationship between the 3′UTR variants, clinicopathological parameters and response to chemotherapy. We analyzed 33 germline polymorphisms in 3′UTRs of ADME genes in 305 breast cancer women treated with FAC regime. Clinical endpoints of this study were: overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS) and overall response defined as treatment failure-free survival (TFFS). The shortened OS was connected with the presence of  NR1/2  rs3732359 AA,  SLC22A16  rs7756222 CC, as well as  SLC22A16  rs9487402 allele G and clinical factors belonging to TNM classification: tumor size >1 cm, nodal involvement and presence of metastases. PFS was related to two polymorphisms  PGR  rs1824125 GG,  PGR  rs12224560 CC and  SLC22A16  rs7756222 CC as well as preexisting metastases. The RFS was shortened due to the  DPYD  rs291593 CC,  AKR1C3  rs3209896 AG and negative expression of PGR. The presence of  ALDH5A1  rs1054899 allele A, lack of pre-chemotherapy surgery and negative status of PGR correlated with worse treatment response. The germline variants commonly present in the population are important factors determining the response to treatment. We observed the effect of the accumulation of genetic and clinical factors on poor survival prognosis and overall treatment response.

Genetic 3′UTR variations and clinical factors significantly contribute to survival prediction and clinical response in breast cancer patients