Association between the genetic polymorphisms of the pharmacokinetics of anthracycline drug and myelosuppression in a patient with breast cancer with anthracycline-based chemotherapy

• Published in: Life sciences (1973) 2021-07, Vol.276, p.119392, Article 119392
• Main Authors: Cui, Lulu, Huang, Jia, Zhan, Yongtao, Qiu, Ni, Jin, Huan, Li, Jia, Huang, Huiqi, Li, Hongsheng
• Format: Article
• Language: English
• Subjects: Adult; Alcohol Oxidoreductases - genetics; Aldehyde Reductase - genetics; Alleles; Anemia; Anthracycline; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics; Biomarkers, Tumor - genetics; Bone Marrow Diseases - chemically induced; Bone Marrow Diseases - epidemiology; Bone Marrow Diseases - pathology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Chemotherapy; China - epidemiology; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Drug metabolism; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic - drug effects; Gene polymorphism; Genetic Predisposition to Disease; Hematologic toxicity; Humans; Leukopenia; Metabolism; Middle Aged; Mutation; Myelosuppression; Neoplasm Proteins - genetics; Neutropenia; Organic Cation Transport Proteins - genetics; Pharmacokinetics; Pharmacology; Polymorphism, Single Nucleotide; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Single nucleotide polymorphism; Survival Rate; Tissue Distribution; Toxicity
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119392

Exploring the genetic polymorphisms involved in the metabolism of anthracyclines can explain the causes of individual differences in myelosuppression during anthracycline-based chemotherapy. By PCR and Sanger sequencing, SNP of candidate genes participating into the pharmacokinetics of anthracycline, including chemotherapeutic drug intake (SLC22A16 rs6907567), metabolism (AKR1A1 rs2088102, CBR1 rs20572) and transfer (ABCG2 rs2231142) are detected in 194 breast cancer patients undergoing anthracycline-based postoperative adjuvant chemotherapy. The CBR1 rs20572 (C>T) polymorphic allele, the ABCG2 rs2231142 (G>T) polymorphic allele, or the two polymorphic allele in combination significantly reduced the risk of leukopenia (OR 0.412, 95% CI 0.187–0.905, p = 0.025) and neutropenia (OR 0.354, 95% CI 0.148–0.846, p = 0.018). Either polymorphic allele T of CBR1 rs20572, or polymorphic allele C of AKR1A1 rs2088102 combined with the presence of both ABCG2 rs2231142(G>T) and SLC22A16 rs6907567(A>G) mutations were at extremely low risk of severe anemia of grades 3 and 4 (OR 0.058, 95% CI 0.006–0.554, p = 0.008, OR 0.065, 95% CI 0.006–0.689, p = 0.022, OR 0.037, 95% CI 0.004–0.36, p = 0.015, respectively). These results suggested CBR1 rs20572, ABCG2 rs2231142, SLC22A16 rs6907567 and AKR1A1 rs2088102 might be potential protective factors for the reduction of hematologic toxicity incidence during anthracycline-based chemotherapy in breast cancer patients.