title: ABCG2 Q141K polymorphism is associated with chemotherapy-induced diarrhea in patients with diffuse large B-cell lymphoma who received frontline rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy.
abstract: ATP-binding cassette transporter G2 (ABCG2) is the most recently described transporter of the multidrug-resistance pump and it promotes resistance to anticancer drugs such as doxorubicin, mitoxantrone, topotecan, and SN-38. Of the ABCG2 polymorphisms, V12M and Q141K alter the functional activity of the ABCG2 transporter and influence the drug response and various toxicities to chemotherapeutic agents. We therefore evaluated the impact of the ABCG2 V12M and Q141K polymorphisms on the therapeutic outcomes and toxicities of primary rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in 145 Korean patients with diffuse large B-cell lymphoma (DLBCL). ABCG2 V12M and Q141K genotyping was carried out by pyrosequencing of polymerase chain reaction products. The clinical characteristics, treatment outcomes, toxicities of the patients, and the predictive value of the polymorphisms on response, survival, and adverse events to R-CHOP for 145 patients were analyzed according to the ABCG2 V12M and Q141K polymorphisms. No differences were observed according to ABCG2 Q141K and V12M genotype in patient characteristics, disease characteristics, response, survival, or hematology toxicity profiles in patients with DLBCL who received frontline R-CHOP chemotherapy. On multivariate analysis, grade I-IV diarrhea was statistically significant according to ABCG2 Q141K polymorphism (the QQ genotype vs the QK or KK genotypes; hazard ratio 2.835; 95% confidence interval 1.432-5.613; P = 0.003). This study demonstrates that the ABCG2 Q141K polymorphism may correlate with chemotherapy-induced diarrhea in patients with DLBCL who have received frontline R-CHOP chemotherapy, and this has implications for optimizing treatment with such agents.
authors.affiliation: Department of Laboratory Medicine, Gyeongsang National University Hospital, 90 Chilam-dong, Jinju 660-702, Korea.
authors.forename: In-Suk
authors.initials: IS
authors.lastname: Kim
authors.forename: Hoon-Gu
authors.initials: HG
authors.lastname: Kim
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Kim
authors.forename: Hyeon-Seok
authors.initials: HS
authors.lastname: Eom
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Hwang
authors.forename: Eun-Yup
authors.initials: EY
authors.lastname: Lee
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Lee
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone