title: Polymorphisms in immune function genes and non-Hodgkin lymphoma survival.
abstract: BACKGROUND
  Cytokines play a critical role in regulating the immune system. In the tumor microenvironment, they influence survival, proliferation, differentiation, and movement of both tumor and stromal cells, and regulate tumor interactions with the extracellular matrix. Given these biologic properties, there is reason to hypothesize that cytokine activity influences the pathogenesis of non-Hodgkin lymphoma (NHL).
  
  
  METHODS
  We investigated the effect of genetic variation in cytokine genes on NHL prognosis and survival by evaluating genetic variation in individual SNPs as well as the combined effect of multiple deleterious genotypes. Survival information from 496 female incident NHL cases diagnosed during 1996-2000 in Connecticut were abstracted from Connecticut Tumor Registry in 2008. Survival analyses were conducted by comparing Kaplan-Meier curves and hazard ratios (HR) were computed using Cox proportional hazard models adjusting for demographic and tumor characteristics for genes that were suggested by previous studies to be associated with NHL survival.
  
  
  RESULTS
  We found that the variant IL6 genotype is significantly associated (HR = 0.42; 95%CI: 0.23-0.77) with a decreased risk of death, as well as relapse and secondary cancer occurrence, among those with NHL. We also found that risk of death, relapse, and secondary cancers varied by specific SNPs for the follicular, DLBCL, and CLL/SLL histologic types. We identified combinations of polymorphisms whose combined deleterious effect significantly alter overall NHL survival and disease-free survival.
  
  
  CONCLUSIONS
  Our study provides evidence that the identification of genetic polymorphisms in cytokine genes may help improve the prediction of NHL survival and prognosis.
authors: School of Public Health, Yale University, New Haven, CT, USA. kilfoyb@mail.nih.gov
authors: Briseis
authors: B
authors: Aschebrook-Kilfoy
authors: Tongzhang
authors: T
authors: Zheng
authors: Francine
authors: F
authors: Foss
authors: Shuangge
authors: S
authors: Ma
authors: Xuesong
authors: X
authors: Han
authors: Qing
authors: Q
authors: Lan
authors: Theodore
authors: T
authors: Holford
authors: Yingtai
authors: Y
authors: Chen
authors: Brian
authors: B
authors: Leaderer
authors: Nathaniel
authors: N
authors: Rothman
authors: Yawei
authors: Y
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003237:Connecticut / Q000453:epidemiology; D016207:Cytokines / Q000235:genetics* / Q000502:physiology; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012959:Socioeconomic Factors; D016019:Survival Analysis; D017741:Survivors; D055815:Young Adult
chemical_list: D016207:Cytokines