title: Effect of CYP2C19 and CYP3A4 gene polymorphisms on the efficacy of bortezomib-based regimens in patients with multiple myeloma.
abstract: Bortezomib is used to treat patients with multiple myeloma. It is primarily metabolized by the enzyme cytochrome P450 (CYP). Variations in the capacity of bortezomib metabolism affect the treatment outcomes and the side-effects experienced by patients. In the present study, polymorphisms in the CYP3A4 and CYP2C19 genes were analyzed by polymerase chain reaction in 56 newly-diagnosed patients with multiple myeloma. The polymorphisms analyzed included the c.681G>A, c.636G>A and c.-806C>T polymorphisms of CYP2C19. The CYP3A4 gene was sequenced after amplification and was classified into normal and mutant types. Associations between the metabolizer genotypes of CYP3A4 and CYP2C19, the therapeutic efficacy of bortezomib-based regimens, and the occurrence of peripheral neuropathy were studied. The results identified no significant differences in gender, serum β2 microglobulin, creatinine, blood albumin, isotypes, and the Durie-Salmon and International Staging System stages between the CYP2C19 poor + intermediate metabolizer types and the extensive + ultrarapid metabolizer types. In addition, it was revealed that the CYP2C19 and CYP3A4 phenotypes did not affect the efficacy of bortezomib-based regimens, nor were they correlated with peripheral neuropathy. Additional large-scale studies are required in order to evaluate the role of CYP enzymes in bortezomib treatments for patients with multiple myeloma.
authors.affiliation: Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: An
authors.affiliation: Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jian
authors.affiliation: Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Chen
keywords: CYP2C19; CYP3A4; bortezomib; peripheral neuropathy; polymorphism