Effect of IL‐6 promoter polymorphism on incidence and outcome in Hodgkin's lymphoma

Cordano, Pablo; Lake, Annette; Shield, Lesley; Taylor, Geoffrey; Alexander, Freda E.; Taylor, Pennie; White, Jo; Jarrett, Ruth F.

doi:10.1111/j.1365-2141.2004.05353.x

Cited by 35 publications

(23 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We examined polymorphisms of six genes controlling cytokine production in 73 patients with AA (Table I) and compared our findings to those of previously published normal controls [3,[6][7][8][9][10][11][12][13][14][15][16]. We found statistically significant increases in the polymorphisms associated with hypersecretion in four (Table II see IFN-g and TNF-a have most clearly been implicated in AA pathophysiology [17].…”

Section: Resultsmentioning

confidence: 76%

Cytokine gene polymorphisms in acquired bone marrow failure

et al. 2007

View full text Add to dashboard Cite

Some acquired aplastic anemia (AA) results from immune‐mediated destruction of hematopoietic stem cells. Cytokine gene polymorphisms are implicated in controlling cytokine production and increasing the susceptibility to some autoimmune diseases. We characterized the IL‐6/‐174, TNF‐α/−308, IL‐10/−1082, IFN‐γ/+874, TGFβ1/−509 single nucleotide polymorphisms (SNP's) and the IL1‐RA second intron variable number tandem repeat (VNTR) alleles in 73 patients with AA and compared the frequency of genotypes to established control populations. We found that some patients with acquired AA have polymorphisms which are linked to high production of proinflammatory cytokines, particularly TNF‐α and IFN‐γ. Am. J. Hematol., 2007. Published 2007 Wiley‐Liss, Inc.

show abstract

Section: Resultsmentioning

confidence: 76%

Cytokine gene polymorphisms in acquired bone marrow failure

et al. 2007

View full text Add to dashboard Cite

show abstract

“…38 In summary, our observations suggest that a decreased ability to produce IL-12 level is a necessary, but not sufficient, determinant of YAHL (because most of the genetically identical unaffected cotwins with low IL-12 levels did not develop disease). Additional factors, perhaps a viral infection and/or other immune system alterations due to early social isolation, are necessary.…”

Section: Discussionmentioning

confidence: 71%

Interleukin-2, interleukin-12, and interferon-γ levels and risk of young adult Hodgkin lymphoma

Cozen

Gill

Salam

et al. 2008

Blood

View full text Add to dashboard Cite

Young adult Hodgkin lymphoma (YAHL)is associated clinically with altered immunity, including a systemic defect in cellmediated responses. There is strong evidence of a genetic contribution to risk, so we hypothesized that heritable alterations in cytokine production associated with Th1 function may contribute to susceptibility. We identified twin pairs in whom at least one member had YAHL and measured interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-␥ (IFN-␥) levels in PHA-stimulated peripheral blood mononuclear cell supernatant in 90 case-twins, 84 of their disease-free twins (unaffected cotwins), and 90 matched controls. Mean difference and mean percentage difference in cytokine levels between casetwins and controls, and unaffected cotwins and controls were determined using analysis of covariance. YAHL casetwins and their unaffected cotwins had IL-12 levels that were 60.6% (P ‫؍‬ .002) and 49% (P ‫؍‬ .04) lower than those of their matched controls, respectively. IL-2 levels were significantly higher in casetwins (P ‫؍‬ .049), but not unaffected cotwins (P ‫؍‬ .57), compared with controls. Differences in IFN-␥ levels were not statistically significant in either comparison. An IL-12 polymorphism known to regulate expression was associated with a 2.8-fold (P ‫؍‬ .03) increase in YAHL risk. Thus, both case-twins and their unaffected cotwins had a decreased ability to produce IL-12, which may contribute to YAHL susceptibility. IntroductionHodgkin lymphoma is characterized by 3 distinctive age-specific incidence peaks associated with different demographic factors, probably representing distinct etiologies. 1 Young adult Hodgkin lymphoma (YAHL), diagnosed approximately from ages 13 to 45 years, consists mainly of an Epstein-Barr virus (EBV)-negative, nodular sclerosis subtype, and has been historically strongly (positively) correlated with higher socioeconomic status and low sibship size. 2 These factors suggest an association between early childhood isolation from infection and risk, consistent with delayed exposure to a common childhood infection ("polio model"). 3 Although Epstein-Barr virus infection would be consistent with this set of factors, the best study to date found no increased risk of EBV-negative Hodgkin lymphoma, the most common type of YAHL, among 40 000 persons with laboratory-documented infectious mononucleosis. 4 (The same study did demonstrate a 20-fold risk of EBV-positive Hodgkin lymphoma within 5 years of the infectious mononucleosis diagnosis, but EBV-positive Hodgkin lymphoma accounts for only 10% to 25% of the disease in young adults.)Genetic factors also contribute to YAHL susceptibility. Excess risk has been reported in siblings 5 and family members 6 of cases, and we found a greater excess risk in identical (monozygotic, MZ) cotwins compared with fraternal (dizygotic, DZ) cotwins of cases. 7 An immune response phenotype associated with altered cytokine levels constitutes a likely candidate for a heritable risk factor since the pathological and clinical hallmark of Hodgkin ly...

show abstract

“…We speculate that BZLF1 is more important than BRLF1 for activation of cIL-10 and IL-6. Polymorphisms in the human IL-10 and IL-6 promoters affect their expression (5,8), and LCLs derived from donors with higher constitutive levels of IL-6 and/or cIL-10 may be less dependent upon BZLF1-activated cytokine production. Of note, the one R-KO LCL (derived from donor 2) that grew efficiently in SCID mice at early passage was also the only R-KO LCL that expressed IL-6 and cIL-10 at a level similar to that of the corresponding WT LCL.…”

Section: Discussionmentioning

confidence: 99%