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Abstract

Title: Host immune gene polymorphisms in combination with clinical and demographic factors predicts late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era.
Author: Habermann TM,Wang SS,Maurer MJ,Morton LM,Lynch CF,Ansell SM,Hartge P,Severson RK,Rothman N,Davis S,Geyer SM,Cozen W,Chanock SJ,Cerhan JR
Journal: Blood
Year: 2008
Month: July

Abstract: To evaluate the hypothesis that host germline 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 immune genes in 365 DLBCL patients diagnosed from 1998-2000. We estimated hazard ratios (HR) and 95% confidence intervals 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 (range, 27-78 months) for surviving patients. The observed survival of this cohort was consistent with population-based estimates conditioned on surviving 12 months. An IL10 haplotype (global p=0.03) and SNPs in IL8RB (rs1126580; HRAG/GG=2.11, 1.28-3.50), IL1A (rs1800587; HRCT/TT=1.90, 1.26-2.87), TNF (rs1800629; HRAG/GG=1.44, 0.95-2.18), and IL4R (rs2107356; HRCC/CT=1.97, 1.01-3.83) were the strongest predictors of overall survival. A risk score that combined the latter four SNPs with clinical factors was strongly associated with survival in a Cox model (p=6.0 X 10(-11)). Kaplan-Meier 5-year survival estimates for low, intermediate-low, intermediate-high, and high risk patients were 94%, 79%, 60%, and 48% respectively. These data support a role for germline variation in immune genes, particularly genes associated with a pro-inflammatory state, as predictors of late survival in DLBCL.