ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP
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Duo Liu1,2, Nan Wu1, Haiming Sun1, Mei Dong2, Tianzhu Guo3, Peng Chi4, Guofu Li5, Donglin Sun1 and Yan Jin1
1Department of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China
2Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
3Department of Pharmacology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
4Department of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang, China
5Department of Neurosurvery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
Yan Jin, email: email@example.com
Donglin Sun, email: firstname.lastname@example.org
Keywords: diffuse large B-cell lymphoma, rituximab, pharmacogenetic, prognosis
Received: October 19, 2016 Accepted: March 09, 2017 Published: April 06, 2017
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele. A significantly shortened PFS (P = 0.013) and EFS (P = 0.002) was also observed in the patients with ABCG2 rs2231137 GG genotype. Furthermore, the elder (> 60 years old) or male patients with ABCG2 rs2231137 GG genotype had poorer PFS and EFS than A allele. Moreover, CD20 rs2070770 CC and RAC2 rs13058338 AT genotypes were independent predictors of chemotherapy-induced toxicity. Cox proportional hazards analyses demonstrated that the GG genotype of ABCG2 rs2231137 and NCF4 rs1883112 were risk factors in DLBCL patients. In conclusion, the identified polymorphisms provide guide for the identification of DLBCL patients who are likely to benefit from chemotherapy.
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