The Association of Pre-diagnostic Inflammatory Markers and Adipokines and the Risk of Non-Hodgkin Lymphoma Development in Egypt

Abstract

Non-Hodgkin lymphoma (NHL) is an etiologically, clinically, and histologically heterogeneous group of lymphoproliferative disorders. Immune dysfunction is a well-known risk factor and dysregulation of cytokines may mediate disease progression. Obesity is one of the important relations connecting immune system abnormalities and lymphomagenesis. We conducted a study to find out the association between obesity as measured by body mass index (BMI), and risk of non-Hodgkin lymphoma (NHL) development by assessment the of inflammatory cytokines levels, (IL-6, IL-10, IFN-gamma and CRP) and adipokines levels (leptin and adiponectin). Also, to predict the effect of higher BMI on the incidence of NHL. The study included 180 NHL patients and 172 healthy controls. The inflammatory markers (IL-6, IL-10, IFN-γ & CRP) together with adiponectin were assessed by ELISA technique. IL-6, IL-10, CRP, IFN-γ and Adiponectin were statistically higher in cases than control. A positive significant difference of Leptin (p-value 0.001) was found with higher levels in patients with BMI (≥ 25 kg/m2) than in patients with < 25 kg/m2. IL-6, IL-10, CRP, IFN-γ and Adiponectin could be implicated in lymphomagenesis in Egyptian NHL. The study results support the hypothesis that obesity has a major role in the development of NHL. An association between Leptin and NHL risk with higher levels in patients with BMI (≥ 25 kg/m2) was proved.

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References

  1. 1.

    Ekstrom SK, Vajdic CM, Falster M et al (2008) Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the inter lymph consortium. Blood 111:4029–4038

    Article  Google Scholar 

  2. 2.

    Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    CAS  Article  Google Scholar 

  3. 3.

    Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–767

    CAS  Article  Google Scholar 

  4. 4.

    Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355

    CAS  Article  Google Scholar 

  5. 5.

    De Pergola G, Silvestris F (2013) Obesity as a major risk factor for cancer. J Obes 2013:291546

    Article  Google Scholar 

  6. 6.

    Vainchenker W, Constantinescu SN (2013) JAK/STAT signaling in hematological malignancies. Oncogene 32:2601–2613

    CAS  Article  Google Scholar 

  7. 7.

    Gopal A, Kahl B, de Vos S, Wagner-Johnston ND, Schuster SJ, Blum KA et al (2014) Mature response data from a phase 2 study of PI3K-delta inhibitor idelalisib in patients with double (rituximab and alkylating agent)-refractory indolent B-cell non-Hodgkin lymphoma (iNHL). Clin Adv Hematol Oncol 12:8–9

    Google Scholar 

  8. 8.

    Beltowski J, Jamroz-Wisniewska A, Widomska S (2008) Adiponectin and its role in cardiovascular diseases. Cardiovasc Hematol Disord Drug Targets 8:7–46

    CAS  Article  Google Scholar 

  9. 9.

    Saxena NK, Sharma D (2010) Metastasis suppression by adiponectin: LKB1 rises up to the challenge. Cell Adh Migr 4:358–362

    Article  Google Scholar 

  10. 10.

    Cerhan JR, Slager SL (2015) Familial predisposition and genetic risk factors for lymphoma. Blood 126:2265–2273

    CAS  Article  Google Scholar 

  11. 11.

    Roberts D, Dive C, Renehan A (2010) Biological mechanisms linking obesity and cancer risk: new perspectives. Ann Rev Med 61:301–316

    CAS  Article  Google Scholar 

  12. 12.

    Renehan AG (2011) Epidemiology of overweight/obesity and cancer risk. In: McTiernan A (ed) Physical activity, dietary calorie restriction, and cancer, vol 3. Springer, New York, pp 5–23

    Google Scholar 

  13. 13.

    Conroy SM, Maskarinec G, Morimoto Y et al (2013) Non-Hodgkin lymphoma and circulating markers of inflammation and adiposity in a nested case-control study: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev 22(3):337–347

    CAS  Article  Google Scholar 

  14. 14.

    Hadi DA, Shani WS, Khalaf AA et al (2013) Serum levels of interleukin-6 and interleukin-10 in adult newly diagnosed Iraqi non-Hodgkin’s lymphoma patients. Euro J Exp Bio 3(5):441–446

    CAS  Google Scholar 

  15. 15.

    Hsu SM, Xie SS, Waldron JA (1992) Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas. Am J Pathol 141(4):915–923

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Purdue MP, Lan Q, Bagni R et al (2011) Prediagnostic serum levels of cytokines and other immune markers and risk of non-Hodgkin Lymphoma. Cancer Res 71(14):4898–4907

    CAS  Article  Google Scholar 

  17. 17.

    Guney N, Soydinc HO, Basaran M et al (2009) Serum levels of interleukin-6 and interleukin-10 in Turkish patients with aggressive non-Hodgkin's lymphoma. Asian Pac J Cancer Prev 10(4):669–674

    PubMed  Google Scholar 

  18. 18.

    Epeldegui M, Widney DP, Martinez-Maza O (2006) Pathogenesis of AIDS lymphoma: role of oncogenic viruses and B cell activation-associated molecular lesions. Curr Opin Oncol 18:444–448

    CAS  Article  Google Scholar 

  19. 19.

    Voorzanger N, Touitou R, Garcia E et al (1996) Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin’s lymphoma cells and act as cooperative growth factors. Cancer Res 56:5499–5505

    CAS  PubMed  Google Scholar 

  20. 20.

    Chen Y, Zheng T, Lan Q et al (2011) Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma. Blood 117:585–590

    CAS  Article  Google Scholar 

  21. 21.

    Saberi HF, Krop EJ, Scoccianti C et al (2010) Plasma cytokines and future risk of non-Hodgkin lymphoma (NHL): a case-control study nested in the Italian European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev 19:1577–1584

    Article  Google Scholar 

  22. 22.

    Shivappa N, He’bert JR, Taborelli M et al (2017) Dietary inflammatory index and non-Hodgkin lymphoma risk in an Italian case–control study. Cancer Causes Control 28:791–799

    Article  Google Scholar 

  23. 23.

    Rothman N, Skibola CF, Wang SS et al (2006) Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the inter lymph consortium. Lancet Oncol 7(1):27–38

    CAS  Article  Google Scholar 

  24. 24.

    La CA, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4:371–379

    Article  Google Scholar 

  25. 25.

    Skibola CF, Holly EA, Forrest MS et al (2004) Body mass index, leptin and leptin receptor polymorphisms, and non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 13(5):779–786

    CAS  PubMed  Google Scholar 

  26. 26.

    Willett EV, Skibola CF, Adamson P et al (2005) Non-Hodgkin’s lymphoma, obesity and energy homeostasis polymorphisms. Br J Cancer 93:811–816

    CAS  Article  Google Scholar 

  27. 27.

    Dalamaga M, Diakopoulos KN, Mantzoros CS (2012) The role of adiponectin in cancer: a review of current evidence. Endocr Rev 33(4):547–594

    CAS  Article  Google Scholar 

  28. 28.

    Petridou ET, Sergentanis TN, Dessypris N et al (2009) Serum adiponectin as a predictor of childhood non-Hodgkin’s lymphoma: a nationwide case-control study. J Clin Oncol 27:5049–5055

    CAS  Article  Google Scholar 

  29. 29.

    Pamuk GE, Turgut B, Demir M et al (2006) Increased adiponectin level in non-Hodgkin lymphoma and its relationship with interleukin-10. Correlation with clinical features and outcome. J Exp Clin Cancer Res 25:537–541

    CAS  PubMed  Google Scholar 

  30. 30.

    Wei T, Ye P, Xin PX et al (2016) circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies. Oncotarget 7(30):48671–48691

    Article  Google Scholar 

  31. 31.

    Hellström L, Wahrenberg H, Hruska K et al (2000) Mechanisms behind gender difference in circulating leptin levels. J Intern Med 247:457–462

    Article  Google Scholar 

  32. 32.

    Kelly JL, Fredericksen ZS, Liebow M et al (2012) The association between early life and adult body mass index and physical activity with risk of non-Hodgkin lymphoma: impact of gender. Ann Epidemiol 22:855–862

    Article  Google Scholar 

  33. 33.

    Patel AV, Diver WR, Teras LR et al (2013) Body mass index, height and risk of lymphoid neoplasms in a large United States cohort. Leuk Lymphoma 54(6):1221–1227

    Article  Google Scholar 

  34. 34.

    Bertrand KA, Giovannucci E, Zhang SM et al (2013) A prospective analysis of body size during childhood, adolescence, and adulthood and risk of non-Hodgkin lymphoma. Cancer Prev Res 6(8):864–873

    Article  Google Scholar 

  35. 35.

    Golubovic I, Marjanovic G, RadojKovic D et al (2017) Overweight, obesity and physical activity in relation to follicular lymphoma incidence and mortality: a meta-analysis. Arch Pathol Clin Res 1:024–034

    Google Scholar 

  36. 36.

    Winer DA, Winer S, Chng MH et al (2014) B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell Mol Life Sci 71:1033–1043

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The work described has not been published previously except in the form of an abstract accepted in the EHA; Inflammation & Adiposity Circulatory Markers In B-Non Hodgkin Lymphoma (B-NHL): An Egyptian Single Center Study: HemaSphere: June 2019—Volume 3—Issue—pp. 933–934. https://doi.org/10.1097/01.HS9.0000566768.18417.3e. Patient number was 45 and 43 healthy controls in the abstract, we increased the number in the original study to 172 patients and 180 healthy control.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Maha Hamdi El Sissy.

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El Demerdash, D.M., Tawfik, N.M., Elazab, R. et al. The Association of Pre-diagnostic Inflammatory Markers and Adipokines and the Risk of Non-Hodgkin Lymphoma Development in Egypt. Indian J Hematol Blood Transfus (2020). https://doi.org/10.1007/s12288-020-01305-9

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Keywords

  • Adipokines
  • NHL
  • Obesity
  • Inflammatory markers
  • Egypt