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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2016; 37(01): 6-13
DOI: 10.4103/0971-5851.177002
REVIEW ARTICLE

Diabetes, Epstein-Barr virus and extranodal natural killer/T-cell lymphoma in India: Unravelling the plausible nexus

Authors

  • Anita Spadigam

    Department of Oral and Maxillofacial Pathology, Goa Dental College and Hospital, Bambolim, Goa, India

  • Anita Dhupar

    Department of Oral and Maxillofacial Pathology, Goa Dental College and Hospital, Bambolim, Goa, India

  • Shaheen Syed

    Department of Oral and Maxillofacial Pathology, Goa Dental College and Hospital, Bambolim, Goa, India

  • Tajindra Saluja

    Department of Oral and Maxillofacial Pathology, Goa Dental College and Hospital, Bambolim, Goa, India

Financial support and sponsorship Nil.
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Abstract

The International Diabetes Federation Diabetes Atlas estimates a staggering 590 million people affected with diabetes mellitus (DM) within the next two decades globally, of which Type 2 DM will constitute more than 90%. The associated insulin resistance, hyperinsulinemia, and hyperglycemia pose a further significant risk for developing diverse malignant neoplasms. Diabetes and malignancy are multifactorial heterogeneous diseases. The immune dysfunction secondary to Type 2 diabetes also reactivates latent infections with high morbidity and mortality rates. Epstein-Barr virus (EBV), a ubiquitous human herpes virus-4, is an oncogenic virus; its recrudescence in the immunocompromised condition activates the expression of EBV latency genes, thus immortalizing the infected cell and giving rise to lymphomas and carcinomas. Extranodal natural killer/T-cell lymphoma (ENKTCL), common in South-East Asia and Latin America; is a belligerent type of non-Hodgkin lymphoma (NHL) almost invariably associated with EBV. An analysis of articles sourced from the PubMed database and Google Scholar web resource until February 2014, suggests an increasing incidence of NHL in Asia/India and of ENKTCL in India, over the last few decades. This article reviews the epidemiological evidence linking various neoplasms with Type 2 DM and prognosticates the emergence of ENKTCL as a common lymphoreticular malignancy secondary to Type 2 diabetes, in the Indian population in the next few decades.

Keywords

Asia - diabetes - Epstein-Barr virus - non-Hodgkin lymphoma - reactivation


Publication History

Article published online:
12 July 2021

© 2016. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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  • References

  • 1 Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103:137-49.
  • 2 Ramachandran A, Snehalatha C, Ma RC. Diabetes in South-East Asia: An update. Diabetes Res Clin Pract 2014;103:231-7.
  • 3 Misra P, Upadhyay RP, Misra A, Anand K. A review of the epidemiology of diabetes in rural India. Diabetes Res Clin Pract 2011;92:303-11.
  • 4 Sadikot SM, Nigam A, Das S, Bajaj S, Zargar AH, Prasannakumar KM, et al. The burden of diabetes and impaired fasting glucose in India using the ADA 1997 criteria: Prevalence of diabetes in India study (PODIS). Diabetes Res Clin Pract 2004;66:293-300.
  • 5 Sadikot SM, Nigam A, Das S, Bajaj S, Zargar AH, Prasannakumar KM, et al. The burden of diabetes and impaired glucose tolerance in India using the WHO 1999 criteria: Prevalence of diabetes in India study (PODIS). Diabetes Res Clin Pract 2004;66:301-7.
  • 6 Beagley J, Guariguata L, Weil C, Motala AA. Global estimates of undiagnosed diabetes in adults. Diabetes Res Clin Pract 2014;103:150-60.
  • 7 Xu ZG, Iwatsuki K, Oyama N, Ohtsuka M, Satoh M, Kikuchi S, et al. The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas. Br J Cancer 2001;84:920-5.
  • 8 Wee J, Nei WL, Yeoh KW, Yeo RM, Loong SL, Qian CN. Why are East Asians more susceptible to several infection-associated cancers (carcinomas of the nasopharynx, stomach, liver, adenocarcinoma of the lung, nasal NK/T-cell lymphomas)? Med Hypotheses 2012;79:833-42.
  • 9 Tlholoe MM, Kotu M, Khammissa RA, Bida M, Lemmer J, Feller L. Extranodal natural killer/T-cell lymphoma, nasal type: ′midline lethal granuloma.′ A case report. Head Face Med 2013;9:4.
  • 10 Aozasa K, Takakuwa T, Hongyo T, Yang WI. Nasal NK/T-cell lymphoma: Epidemiology and pathogenesis. Int J Hematol 2008;87:110-7.
  • 11 Sankaranarayanan R, Ramadas K, Qiao YL. Managing the changing burden of cancer in Asia. BMC Med 2014;12:3.
  • 12 Vallabhajosyula S, Baijal G, Vadhiraja BM, Fernandes DJ, Vidyasagar MS. Non-Hodgkin′s lymphoma: Is India ready to incorporate recent advances in day to day practice? J Cancer Res Ther 2010;6:36-40.
  • 13 Sahni CS, Desai SB. Distribution and clinicopathologic characteristics of non-Hodgkin′s lymphoma in India: A study of 935 cases using WHO classification of lymphoid neoplasms (2000). Leuk Lymphoma 2007;48:122-33.
  • 14 Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin′s lymphoma in India: A study of 2773 lymphomas using R.E.A.L. and WHO Classifications. Ann Oncol 2000;11 Suppl 1:63-7.
  • 15 Yeole BB. Trends in the incidence of Non-Hodgkin′s lymphoma in India. Asian Pac J Cancer Prev 2008;9:433-6.
  • 16 Deepa M, Bhansali A, Anjana RM, Pradeepa R, Joshi SR, Joshi PP, et al. Knowledge and awareness of diabetes in urban and rural India: The Indian Council of Medical Research India Diabetes Study (Phase I): Indian Council of Medical Research India Diabetes 4. Indian J Endocrinol Metab 2014;18:379-85.
  • 17 Neel JV. Diabetes mellitus: A "thrifty" genotype rendered detrimental by "progress"? Am J Hum Genet 1962;14:353-62.
  • 18 Yajnik CS. Fetal origins of diabetes in developing countries. Diabetes Voice 2003;48:36-8.
  • 19 Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007;125:217-30.
  • 20 Radha V, Mohan V. Genetic predisposition to type 2 diabetes among Asian Indians. Indian J Med Res 2007;125:259-74.
  • 21 Gallagher EJ, LeRoith D. Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 2013;36 Suppl 2:S233-9.
  • 22 D′Amico AV, Braccioforte MH, Moran BJ, Chen MH. Causes of death in men with prevalent diabetes and newly diagnosed high- versus favorable-risk prostate cancer. Int J Radiat Oncol Biol Phys 2010;77:1329-37.
  • 23 Schrauder MG, Fasching PA, Häberle L, Lux MP, Rauh C, Hein A, et al. Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol 2011;137:975-83.
  • 24 Varlotto J, Medford-Davis LN, Recht A, Flickinger J, Schaefer E, Shelkey J, et al. Confirmation of the role of diabetes in the local recurrence of surgically resected non-small cell lung cancer. Lung Cancer 2012;75:381-90.
  • 25 Stein KB, Snyder CF, Barone BB, Yeh HC, Peairs KS, Derr RL, et al. Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: A systematic review and meta-analysis. Dig Dis Sci 2010;55:1839-51.
  • 26 López-Lázaro M. The warburg effect: Why and how do cancer cells activate glycolysis in the presence of oxygen? Anticancer Agents Med Chem 2008;8:305-12.
  • 27 Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004;4:891-9.
  • 28 Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74.
  • 29 Pikor L, Thu K, Vucic E, Lam W. The detection and implication of genome instability in cancer. Cancer Metastasis Rev 2013;32:341-52.
  • 30 Ma H, Zhou Z, Wei S, Liu Z, Pooley KA, Dunning AM, et al. Shortened telomere length is associated with increased risk of cancer: A meta-analysis. PLoS One 2011;6:e20466.
  • 31 Adaikalakoteswari A, Balasubramanyam M, Mohan V. Telomere shortening occurs in Asian Indian Type 2 diabetic patients. Diabet Med 2005;22:1151-6.
  • 32 Gardner JP, Li S, Srinivasan SR, Chen W, Kimura M, Lu X, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005;111:2171-7.
  • 33 El-Wassef M, El-Saeed GS, El-Tokhy SE, Raslan HM, Tawfeek S, Siam I, et al. Oxidative DNA damage in patients with type 2 diabetes mellitus. Diabetol Croat 2012;41:121-7.
  • 34 Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activities in cultured cancer cells. Diabetes Metab Res Rev 2009;25:41-9.
  • 35 Kurtzhals P, Schäffer L, Sørensen A, Kristensen C, Jonassen I, Schmid C, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000;49:999-1005.
  • 36 Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer 2009;16:1103-23.
  • 37 Novosyadlyy R, Lann DE, Vijayakumar A, Rowzee A, Lazzarino DA, Fierz Y, et al. Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Res 2010;70:741-51.
  • 38 LeRoith D, Roberts CT Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127-37.
  • 39 Heuson JC, Legros N, Heimann R. Influence of insulin administration on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in intact, oophorectomized, and hypophysectomized rats. Cancer Res 1972;32:233-8.
  • 40 Kaaks R, Lukanova A. Energy balance and cancer: The role of insulin and insulin-like growth factor-I. Proc Nutr Soc 2001;60:91-106.
  • 41 Gallagher EJ, LeRoith D. The proliferating role of insulin and insulin-like growth factors in cancer. Trends Endocrinol Metab 2010;21:610-8.
  • 42 Neely EK, Morhenn VB, Hintz RL, Wilson DM, Rosenfeld RG. Insulin-like growth factors are mitogenic for human keratinocytes and a squamous cell carcinoma. J Invest Dermatol 1991;96:104-10.
  • 43 Wu Y, Brodt P, Sun H, Mejia W, Novosyadlyy R, Nunez N, et al. Insulin-like growth factor-I regulates the liver microenvironment in obese mice and promotes liver metastasis. Cancer Res 2010;70:57-67.
  • 44 Kaaks R. Nutrition, insulin, IGF-1 metabolism and cancer risk: A summary of epidemiological evidence. Novartis Found Symp 2004;262:247-60.
  • 45 Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R, et al. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res 1997;57:4667-72.
  • 46 Wu Y, Cui K, Miyoshi K, Hennighausen L, Green JE, Setser J, et al. Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Res 2003;63:4384-8.
  • 47 Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res 2002;62:1030-5.
  • 48 Cusi K, Maezono K, Osman A, Pendergrass M, Patti ME, Pratipanawatr T, et al. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest 2000;105:311-20.
  • 49 Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, et al. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J Clin Invest 1999;104:447-57.
  • 50 Stattin P, Björ O, Ferrari P, Lukanova A, Lenner P, Lindahl B, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care 2007;30:561-7.
  • 51 Zhou XH, Qiao Q, Zethelius B, Pyörälä K, Söderberg S, Pajak A, et al. Diabetes, prediabetes and cancer mortality. Diabetologia 2010;53:1867-76.
  • 52 Masur K, Vetter C, Hinz A, Tomas N, Henrich H, Niggemann B, et al. Diabetogenic glucose and insulin concentrations modulate transcriptome and protein levels involved in tumour cell migration, adhesion and proliferation. Br J Cancer 2011;104:345-52.
  • 53 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813-20.
  • 54 Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A 2010;107:8788-93.
  • 55 Son Y, Cheong YK, Kim NH, Chung HT, Kang DG, Pae HO. Mitogen-activated protein kinases and reactive oxygen species: How can ROS activate MAPK pathways? J Signal Transduct 2011;2011:792639.
  • 56 Vaughn AE, Deshmukh M. Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c. Nat Cell Biol 2008;10:1477-83.
  • 57 Yeluri S, Madhok B, Prasad KR, Quirke P, Jayne DG. Cancer′s craving for sugar: An opportunity for clinical exploitation. J Cancer Res Clin Oncol 2009;135:867-77.
  • 58 Plouffe JF, Silva J Jr., Fekety R, Allen JL. Cell-mediated immunity in diabetes mellitus. Infect Immun 1978;21:425-9.
  • 59 Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol 1999;26:259-65.
  • 60 Lecube A, Pachón G, Petriz J, Hernández C, Simó R. Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement. PLoS One 2011;6:e23366.
  • 61 Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocrinol Metab 2012;16 Suppl 1:S27-36.
  • 62 Osar Z, Samanci T, Demirel GY, Damci T, Ilkova H. Nicotinamide effects oxidative burst activity of neutrophils in patients with poorly controlled type 2 diabetes mellitus. Exp Diabesity Res 2004;5:155-62.
  • 63 Berrou J, Fougeray S, Venot M, Chardiny V, Gautier JF, Dulphy N, et al. Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes. PLoS One 2013;8:e62418.
  • 64 Kumar M, Roe K, Nerurkar PV, Namekar M, Orillo B, Verma S, et al. Impaired virus clearance, compromised immune response and increased mortality in type 2 diabetic mice infected with West Nile virus. PLoS One 2012;7:e44682.
  • 65 de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: A review and synthetic analysis. Lancet Oncol 2012;13:607-15.
  • 66 Leenman EE, Panzer-Grümayer RE, Fischer S, Leitch HA, Horsman DE, Lion T, et al. Rapid determination of Epstein-Barr virus latent or lytic infection in single human cells using in situ hybridization. Mod Pathol 2004;17:1564-72.
  • 67 Engels EA. Infectious agents as causes of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 2007;16:401-4.
  • 68 Maeda E, Akahane M, Kiryu S, Kato N, Yoshikawa T, Hayashi N, et al. Spectrum of Epstein-Barr virus-related diseases: A pictorial review. Jpn J Radiol 2009;27:4-19.
  • 69 Rezk SA, Weiss LM. Epstein-Barr virus-associated lymphoproliferative disorders. Hum Pathol 2007;38: 1293-304.
  • 70 Werner M, Ernberg I, Zou J, Almqvist J, Aurell E. Epstein-Barr virus latency switch in human B-cells: A physico-chemical model. BMC Syst Biol 2007;1:40.
  • 71 Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer 2004;4:757-68.
  • 72 Cohen JI. Epstein-Barr virus infection. N Engl J Med 2000;343:481-92.
  • 73 Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol 2002;12:421-9.
  • 74 Meng W, Zhou Y, Zhang H, Jiang L, Wang Z, Li X, et al. Nasal-type NK/T-cell lymphoma with palatal ulcer as the earliest clinical manifestation: A case report with literature review. Pathol Oncol Res 2010;16:133-7.
  • 75 Li S, Feng X, Li T, Zhang S, Zuo Z, Lin P, et al. Extranodal NK/T-cell lymphoma, nasal type: A report of 73 cases at MD Anderson Cancer Center. Am J Surg Pathol 2013;37:14-23.
  • 76 Martelius T, Lappalainen M, Palomäki M, Anttila VJ. Clinical characteristics of patients with Epstein Barr virus in cerebrospinal fluid. BMC Infect Dis 2011;11:281.
  • 77 Wilson WH, Kingma DW, Raffeld M, Wittes RE, Jaffe ES. Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. Blood 1996;87:4531-7.
  • 78 LaCasce AS. Post-transplant lymphoproliferative disorders. Oncologist 2006;11:674-80.
  • 79 Kulwichit W, Edwards RH, Davenport EM, Baskar JF, Godfrey V, Raab-Traub N. Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice. Proc Natl Acad Sci U S A 1998;95:11963-8.
  • 80 Kamranvar SA, Masucci MG. The Epstein-Barr virus nuclear antigen-1 promotes telomere dysfunction via induction of oxidative stress. Leukemia 2011;25:1017-25.
  • 81 Widmann TA, Herrmann M, Taha N, König J, Pfreundschuh M. Short telomeres in aggressive non-Hodgkin′s lymphoma as a risk factor in lymphomagenesis. Exp Hematol 2007;35:939-46.
  • 82 Novelli S, Briones J, Sierra J. Epidemiology of lymphoid malignancies: Last decade update. Springerplus 2013;2:70.
  • 83 Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 1994;84:1361-92.
  • 84 Zerbini MCN, Soares FA, Velloso EDRP, Chaufaille MF, Paes RP. World Health Organization classification of tumors of hematopoietic and lymphoid tissues, 4 th edition, 2008 - major changes from the 3 rd edition, 2001. Rev Assoc Med Bras 2011;57:66-73.
  • 85 Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, et al. Nonnasal lymphoma expressing the natural killer cell marker CD56: A clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 1997;89:4501-13.
  • 86 Takakuwa T, Dong Z, Nakatsuka S, Kojya S, Harabuchi Y, Yang WI, et al. Frequent mutations of Fas gene in nasal NK/T cell lymphoma. Oncogene 2002;21:4702-5.
  • 87 Liang R. Advances in the management and monitoring of extranodal NK/T-cell lymphoma, nasal type. Br J Haematol 2009;147:13-21.
  • 88 Ohshima K, Suzumiya J, Shimazaki K, Kato A, Tanaka T, Kanda M, et al. Nasal T/NK cell lymphomas commonly express perforin and Fas ligand: Important mediators of tissue damage. Histopathology 1997;31:444-50.
  • 89 Kojima H, Takei N, Mukai Y, Hasegawa Y, Suzukawa K, Nagata M, et al. Hemophagocytic syndrome as the primary clinical symptom of Hodgkin′s disease. Ann Hematol 2003;82:53-6.
  • 90 Kim J, Kim EY, Lee SK, Kim DI, Kim CH, Kim SH, et al. Extranodal nasal-type NK/T-cell lymphoma: Computed tomography findings of head and neck involvement. Acta Radiol 2010;51:164-9.
  • 91 Tababi S, Kharrat S, Sellami M, Mamy J, Zainine R, Beltaief N, et al. Extranodal NK/T-cell lymphoma, nasal type: Report of 15 cases. Eur Ann Otorhinolaryngol Head Neck Dis 2012;129:141-7.