Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.

in Blood by 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

TLDR

  • This study looked at how certain changes in genes related to the immune system could predict how long people with a type of cancer called follicular lymphoma would live.
  • The study found that changes in four specific genes were the best predictors of how long people with follicular lymphoma would live.
  • These changes could be used to help doctors predict how long their patients will live and to help them make better treatment decisions.

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.

Overview

  • The study evaluates the hypothesis that germ line common variation in candidate immune genes is associated with survival in patients with follicular lymphoma.
  • 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.

Comparative Analysis & Findings

  • 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.

Implications and Future Directions

  • Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.
  • The study identifies four SNPs in immune genes that are robust predictors of survival in follicular lymphoma.
  • Future research should focus on validating these findings in larger cohorts and exploring the underlying biological mechanisms that link immune genetic signatures to outcomes in patients with follicular lymphoma.
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