Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

James R Cerhan; Sophia Wang; Matthew J Maurer; Stephen M Ansell; Susan M Geyer; Wendy Cozen; Lindsay M Morton; Scott Davis; Richard K Severson; Nathaniel Rothman; Charles F Lynch; Sholom Wacholder; Stephen J Chanock; Thomas M Habermann; Patricia Hartge

doi:10.1182/blood-2006-11-058040

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Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

Journal article

Open access

Peer reviewed

Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

James R Cerhan, Sophia Wang, Matthew J Maurer, Stephen M Ansell, Susan M Geyer, Wendy Cozen, Lindsay M Morton, Scott Davis, Richard K Severson, Nathaniel Rothman, …

Blood, Vol.109(12), pp.5439-5446

06/15/2007

DOI: 10.1182/blood-2006-11-058040

PMCID: PMC1890834

PMID: 17327408

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Abstract

Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line 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 after accounting 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; HR(TT)=2.14, 1.26-3.63), IL2 (rs2069762; HR(GT/TT) = 1.80, 1.06-3.05), IL12B (rs3212227; HR(AC/CC)=1.83, 1.06-3.06), and IL1RN (rs454078; HR(AA)=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=.001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P<.001); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%), and 58% (48%-72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.

Predictive Value of Tests

Prognosis

Humans

Middle Aged

Lymphoma, Follicular - diagnosis

Proportional Hazards Models

Survivors

Lymphoma, Follicular - mortality

Survival Rate

Interleukins - genetics

Lymphoma, Follicular - genetics

Adult

Aged

Polymorphism, Single Nucleotide

Immunity - genetics

Details

Title: Subtitle: Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival
Creators: James R Cerhan - Mayo Clinic College of Medicine, Rochester, MN 55905, USA. cerhan.james@mayo.edu
Sophia Wang
Matthew J Maurer
Stephen M Ansell
Susan M Geyer
Wendy Cozen
Lindsay M Morton
Scott Davis
Richard K Severson
Nathaniel Rothman
Charles F Lynch
Sholom Wacholder
Stephen J Chanock
Thomas M Habermann
Patricia Hartge
Resource Type: Journal article
Publication Details: Blood, Vol.109(12), pp.5439-5446
DOI: 10.1182/blood-2006-11-058040
PMID: 17327408
PMCID: PMC1890834
NLM abbreviation: Blood
ISSN: 0006-4971
eISSN: 1528-0020
Publisher: United States
Grant note: N01 PC067010 / NCI NIH HHS Intramural NIH HHS N01 PC067008 / NCI NIH HHS P50 CA97274 / NCI NIH HHS N01 PC065064 / NCI NIH HHS N01 PC067009 / NCI NIH HHS R01 CA096704 / NCI NIH HHS R01 CA96704 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
Language: English
Date published: 06/15/2007
Academic Unit: Epidemiology
Record Identifier: 9983995141402771

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