ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP
ONCOTARGET
Authors: Liu, Duo; Wu, Nan; Sun, Haiming; Dong, Mei; Guo, Tianzhu; Chi, Peng; Li, Guofu; Sun, Donglin; Jin, Yan
Abstract
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.
Common variants in genes that mediate immunity and risk of multiple myeloma
INTERNATIONAL JOURNAL OF CANCER
Authors: Brown, Elizabeth E.; Lan, Qing; Zheng, Tongzhang; Zhang, Yawei; Wang, Sophia S.; Hoar-Zahm, Shelia; Chanock, Stephen J.; Rothman, Nathaniel; Baris, Dalsu
Abstract
Multiple myeloma (MM) is a B-cell malignancy characterized by aberrant immune function. Using genomic DNA extracted from 127 MM cases aged 21-84 years and 545 population-based controls, we examined the risks of MM associated with 82 common variants in 45 genes that mediate immunity among women of European American descent. Genotyping was determined using validated and optimized TaqMan assays. We estimated haplotype frequencies from unphased genotype data for 20 of these genes using the expectation-maximization progressive insertion algorithm. Compared with controls, MM risk was positively associated with homozygotes of single loci, IL4R (-28120T, rs2107356) and FCGR2A (-120G, rs1801274) (OR = 1.91, 95% CI 1.08-3.38 and 1-95, 95% CI 1.06-3.60, respectively). For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering, part of the LTA*TNF complex (LTA -82C/-90G *TNF -1036C/-487G/ -417G, OR = 1.63, 95% CI 1.02-2.16) compared with the most frequently occurring haplotype observed among controls (LTA -82A/-90A *TNF -1036C/-487G./-417G). Our findings provide preliminary evidence that common genetic variants in specific immune-mediaied pathways could influence the risk of MM. (c) 2007 Wiley-Liss, Inc.