Common Genetic Variants in Proinflammatory and Other Immunoregulatory Genes and Risk for Non-Hodgkin Lymphoma

Wang, Sophia; Cerhan, James R.; Hartge, Patricia; Davis, Scott; Cozen, Wendy; Severson, Richard K.; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J.; Rothman, Nathaniel

doi:10.1158/0008-5472.can-06-0324

Cited by 120 publications

(134 citation statements)

References 59 publications

(54 reference statements)

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“…30 Cytokines present within the tumor microenvironment appear to contribute to growth and survival of malignant cells and also ensures a continued inflammatory milieu recruiting reactive cells to lymphoma tissue. [31][32][33] Elevations in various cytokines have been reported as markers of aggressive lymphoma. 34,35 Some of these cytokines may represent interdependent cascades with synergistic effects and others may be downstream of one principal cytokine.…”

Section: Discussionmentioning

confidence: 99%

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Mir¹,

Maurer²,

Ziesmer³

et al. 2015

Blood

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• Elevated IL-2R, IL-1RA, and CXCL9 are associated with shorter event-free survival in newly diagnosed FL, treated with chemoimmunotherapy.• Increased serum IL-12 and IL-1RA is associated with shorter event-free survival in patients who were observed or treated with rituximab alone.Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n 5 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy.Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P 5 .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P 5 .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P 5 .013, .042, and .0012) were associated with a poor EFS. (Blood. 2015;125(6):992-998) Introduction Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the United States.1 While classified as an indolent B-cell lymphoma, the clinical course exhibits a spectrum based on the FL international prognostic index (FLIPI) score with a remarkable tendency for patients to relapse.2 The overall survival rate of patients with FL was previous reported as 75% at 5 years, and ranged from 71% at 10 years for patients with a FLIPI score between 0 to 1, and 36% for those with a FLIPI score of .3. Currently, the median survival of all newly diagnosed patients is approximately 9 years. 3Although the overall survival appears to have improved with advances in chemoimmunotherapy, the median event free survival (EFS) remains around 2 years for patients with advanced disease. 4 As a prognostic score, the FLIPI has several limitations. It focuses on clinical factors and does not take into account biological factors such as the tumor microenvironment and the host response. Indeed, some studies have found better prognostication of the very high-risk group with the international prognostic index (IPI) rather than with the FLIPI. 5,6 The FLIPI may potentially be further improved, particularly in the high-risk categories, if biological data are added. Gene expression profiling studies on pretreatment specimens from patients with FL hav...

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Section: Discussionmentioning

confidence: 99%

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Mir¹,

Maurer²,

Ziesmer³

et al. 2015

Blood

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“…Similar work has identified a potential role for SNPs in the genes encoding IL8, IL2, IL12B, and IL1RN in patients with follicular lymphoma (FL). 15 Other work has identified polymorphisms in several immunoregulatory genes 16 and HLA 17 as potential contributing factors in patients with lymphoma.…”

Section: Genetic Risk Factorsmentioning

confidence: 99%

Host Factors for Risk and Survival in Lymphoma

Davé

2010

Hematology

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All cancers arise from complex interactions between aspects of the patient (host) biology and the environment. Once tumors arise, they frequently remain dependent on interactions with their microenvironment for their growth and proliferation. In this review, we examine the contributions of the host genetics and environmental exposures to the development of lymphoma. We will further examine the interactions of the tumor and the microenvironment that influence tumor growth and proliferation.Most tumor cells cannot survive for long when taken outside their immediate environment. This indicates a level of dependence on secreted factors or direct cellular interactions with the microenvironment that provides survival signals. This dependence may arise from normal interactions of the normal cell counterpart or it might arise from new, abnormal interactions that arise from the tumor biology. The precancer host biology itself may have a role in either promoting tumor growth or permissive growth by either harboring polymorphisms that, in the right context, promote tumor growth, or through behaviors that increase exposure to elements that promote carcinogenesis.Emerging technologies have provided new insights into the biology of a number of lymphomas. These technologies include microarrays that have enabled gene expression profiling to define the role of malignant and nonmalignant cells in the biology of lymphomas.Herein, we review the known contribution of the tumor microenvironment and host biology to the risk of developing lymphoma and the role of inherited and acquired host factors in disease progression and prognosis in patients with lymphoma. We will examine the tumor "macro" environment (ie, the biology of the patient [host]) and the tumor "micro" environment that contribute to the observed malignant phenotype.

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“…[14][15][16] Common genetic variants in cytokine and other immune genes have been associated with the risk of developing NHL in case-control studies. [17][18][19][20][21][22] In addition, some of these variants have also been associated with progression-free or overall NHL survival in prognostic cohort studies. 20,21,23,24 However, studies of prognosis after diagnosis have been limited to an evaluation of a small number of genes (Յ 3) in small numbers of patients with follicular lymphoma (Ͻ 125).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

Cerhan

Wang

Maurer

et al. 2007

Blood

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108

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Common Genetic Variants in Proinflammatory and Other Immunoregulatory Genes and Risk for Non-Hodgkin Lymphoma

Cited by 120 publications

References 59 publications

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Host Factors for Risk and Survival in Lymphoma

Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

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