Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era

Abstract

To evaluate the hypothesis that host germ line variation in immune genes is associated with overall survival in diffuse large B-cell lymphoma (DLBCL), we genotyped 73 single nucleotide polymorphisms (SNPs) from 44 candidate genes in 365 DLBCL patients diagnosed from 1998 to 2000. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of SNPs with survival after adjusting for clinical factors. During follow-up, 96 (26%) patients died, and the median follow-up was 57 months for surviving patients. The observed survival of this cohort was consistent with populationbased estimates conditioned on surviving 12 months. An IL10 haplotype (global P=.03) and SNPs in IL8RB (rs1126580; HRag/gg=2.11; Cl, 1.28-3.50), IL1A (rs1800587; HRCT/TT=1-90; Cl, 1.26-2.87), TNF (rs1800629; HRAG/GG=1. 44; Cl, 0.95-2.18), and IL4R (rs2107356; HRcc/ct=1.97; Cl, 1.01-3.83) were the strongest predictors of overall survival. A risk score that combined the latter 4 SNPs with clinical factors was strongly associated with survival in a Cox model (P= 6.0 × 10-11). Kaplan-Meier 5-year survival estimates for low, intermediatelow, intermediate-high, and high-risk patients were 94%, 79%, 60%, and 48%, respectively. These data support a role for germ line variation in immune genes, particularly genes associated with a proinflammatory state, as predictors of late survival in DLBCL. © 2008 by The American Society of Hematology.