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.
Genetic risk factors for infection in patients with early rheumatoid arthritis
GENES AND IMMUNITY
Authors: Hughes, LB; Criswell, LA; Beasley, TM; Edberg, JC; Kimberly, RP; Moreland, LW; Seldin, MF; Bridges, SL
Abstract
We analyzed clinical and genetic factors contributing to infections in 457 subjects with early rheumatoid arthritis ( RA) enrolled in a prospective, 1-year clinical trial of methotrexate and the TNF inhibitor etanercept. Subjects were genotyped for the following single nucleotide polymorphisms (SNPs): ( TNF - 308, + 238, and +488); lymphotoxin-alpha (LTA) (LTA +249, +365, and +720); and Fc gamma receptors FCGR2A 131 H/R; FCGR3A 176 F/V; and FCGR3B NA 1/2 and genotypes were correlated with infections. At least one URI was noted in 52% of subjects (99/191) with the NA2/NA2 genotype of the neutrophil-specific FCGR3B gene, compared to 42% (77/181) of those with the NA1/NA2 genotype and 39% (23/59) of those with the NA1/ NA1 genotype ( P = 0.038). Urinary tract infection (UTI) was associated with the TNF - 238 A (odds ratio(OR) 2.56, 95% confidence interval (CI) 1.05 - 6.25) and LTA +365 C (OR 1.73, 95% CI 1.07 - 2.79) alleles, and marginally with the FCGR3A F allele (OR 1.72, 95% CI 0.99 - 3.00). There was a striking linear correlation between UTI and the number of risk alleles defined by these three SNPs (P<0.001), suggesting an additive effect on susceptibility. These findings have important implications for the role of genetics in susceptibility to bacterial and viral infections.