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Abstract

Title: Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
Author: Cerhan JR, Wang S, Maurer MJ, Ansell SM, Geyer SM, Cozen W, Morton LM, Davis S, Severson RK, Rothman N, Lynch CF, Wacholder S, Chanock SJ, Habermann TM, Hartge P
Journal: Blood 109:5439-5446
Year: 2007
Month: February

Abstract: Recent gene expression data have suggested that host immune genetic signatures may predict outcome in patients with follicular lymphoma. We evaluated the hypothesis that germline common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs, adjusting for age, clinical and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HRTT=2.14, 1.26-3.63), IL2 (rs2069762; HRGT/TT=1.80, 1.06-3.05), IL12B (rs3212227; HRAC/CC=1.83, 1.06-3.06), and IL1RN (rs454078; HRAA=1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (p=0.001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (p=1.8 X 10(-11)); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%) and 58% (48%-72%) for low, intermediate, and high risk groups respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.