Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium

Rothman, Nathaniel; Skibola, Christine F.; Wang, Sophia; Morgan, Gareth J.; Lan, Qing; Smith, Martyn T.; Spinelli, John J.; Willett, Eleanor V.; Sanjosé, Sílvia de; Cocco, Pierluigi; Berndt, Sonja I.; Brennan, Paul; Brooks‐Wilson, Angela; Wacholder, Sholom; Becker, Nikolaus; Hartge, Patricia; Zheng, Tongzhang; Roman, Eve; Holly, Elizabeth A.; Boffetta, Paolo; Armstrong, Beth; Cozen, Wendy; Linet, Martha S.; Bosch, Franz X.; Ennas, Maria Grazia; Holford, Theodore R.; Gallagher, Richard P.; Rollinson, Sara; Bracci, Paige M.; Cerhan, James R.; Whitby, Denise; Moore, Patrick S.; Leaderer, Brian P.; Lai, Agnes S.; Spink, Charlotte F.; Davis, Scott; Bosch, Ramón; Scarpa, Aldo; Zhang, Yawei; Severson, Richard K.; Yeager, Meredith; Chanock, Stephen J.; Nieters, Alexandra

doi:10.1016/s1470-2045(05)70434-4

Cited by 333 publications

(349 citation statements)

References 48 publications

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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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“…In a pooled analysis of 8 European, Canadian, and US case-control studies of NHL, single nucleotide polymorphisms (SNPs) in tumor necrosis factor (TNF) and interleukin-10 (IL10), genes encoding key cytokines involved in the inflammatory response and immune balance, were associated with risk of NHL, especially diffuse large B-cell lymphoma. 481 SNPs in 7 other genes involved in the immune and inflammatory response, however, were not associated with NHL risk. The positive association with genetic variation in IL10 was also found independently in one of the US studies included in the pooled analysis.…”

Section: Genetic Variationmentioning

confidence: 94%

The non-Hodgkin lymphomas: A review of the epidemiologic literature

et al. 2007

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“…Several studies have shown a link between polymorphisms in IL-1b, IL-6, IL-10, COX-2, NF-kB and PPARg and cancer risk. [4][5][6][7][8] They may also be central to the pathogenesis of MM. New treatment strategies directed against these targets are being developed, and inborn variations in these genes may therefore become essential for the effect of such targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

The polymorphism IL-1β T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

Vangsted

Klausen

Ruminski

et al. 2008

Bone Marrow Transplant

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Proinflammatory cytokines are suspected to play a role in the pathogenesis of multiple myeloma (MM). Therefore, it is possible that inborn genetic variations leading to a modified expression of these cytokines will influence the outcome for these patients. We investigated 348 MM patients undergoing high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1b T-31C significantly influenced overall survival (OS; P ¼ 0.02) and that carriers of the variant C-allele had a significantly longer survival than homozygous wild-type allele TT-carriers (relative risk 0.6 (95% CI ¼ 0.5-0.9); P ¼ 0.008). The polymorphisms IL-6 G-174C, IL-10 C592A, PPARc2 Pro 12 Ala, COX-2 A-1195G, COX-2 T8473C and NFKB1 ins/del did not influence the OS in this group of patients. Furthermore, homozygous carriers of the variant allele of IL-1b T-31C were at 1.37-fold (CI ¼ 1.05-1.80) increased risk of MM as compared with population-based controls (P ¼ 0.02). Our results indicate that IL-1b is involved in the pathogenesis of MM.

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Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium

Cited by 333 publications

References 48 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

The non-Hodgkin lymphomas: A review of the epidemiologic literature

The polymorphism IL-1β T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

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