Gene Polymorphisms And Vincristine-Induced Neuropathy In Patients Who Received R-Chop Chemotherapy

Background: Rituximab with cyclophosphamide, doxorubicin, vincristine (VCR), and prednisone (R-CHOP) chemotherapy is the standard regimen for newly diagnosed diffuse large B-cell lymphoma (DLBCL). VCR has been widely used in the treatment of lymphoid malignancies and is included in R-CHOP. However, VCR causes peripheral neuropathy (PN), which is one of major toxicities that reduce quality of life. VCR-induced PN (VIPN) is associated with the VCR dose, vincristine cumulative dose, age, and comorbidities (e.g., impaired glucose tolerance). During the last decade, more than 10 gene polymorphisms have been reported to be associated with VIPN in studies of children with acute lymphoblastic leukemia (ALL) who were treated with VCR-containing regimens. Among these polymorphisms, CEP72 rs924607 TT, MTNR1B rs12786200, and ETAA1 rs17032980 were associated with VIPN in both children and adult patients (pts) with ALL in a North American cohort. In a few studies of children with ALL outside the US, the CEP72 rs924607 TT genotype was not associated with VIPN, suggesting an ethnic deviation in the association. Recent studies including children with ALL have also reported that CYP3A5 rs776746, rs7963521, and rs1045644 are associated with VIPN. Little is known about the association between these gene polymorphisms and VIPN in adult pts with B-cell lymphoma. The present study aimed to elucidate the relation between VIPN in adult pts with lymphoma and the CEP72 rs924607, MTNR1B rs12786200, ETAA1 rs17032980, CYP3A5 rs776746, rs7963521, and rs1045644 polymorphisms.