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Tumor Biology

, Volume 37, Issue 1, pp 271–281 | Cite as

Study of single nucleotide polymorphisms of tumour necrosis factors and HSP genes in nasopharyngeal carcinoma in North East India

  • Meena Lakhanpal
  • Laishram Chandreshwor Singh
  • Tashnin Rahman
  • Jagnnath Sharma
  • M. Madhumangal Singh
  • Amal Chandra Kataki
  • Saurabh Verma
  • Santhi Latha Pandrangi
  • Y. Mohan Singh
  • Saima Wajid
  • Sujala Kapur
  • Sunita Saxena
Original Article

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial tumour with a distinctive racial and geographical distribution. High incidence of NPC has been reported from China, Southeast Asia, and northeast (NE) region of India. The immune mechanism plays incredibly role in pathogenesis of NPC. Tumour necrosis factors (TNFs) and heat shock protein 70 (HSP 70) constitute significant components of innate as well as adaptive host immunity. Multi-analytical approaches including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR) were applied in 120 NPC cases and 100 controls to explore high order interactions among TNF-α (−308 G>A), TNF β (+252 A>G), HSP 70-1 (+190 G>C), HSP 70-hom (+2437 T>C) genes and environmental risk factors. TNF β was identified as the primary etiological factor by all three analytical approaches. Individual analysis of results showed protective effect of TNF β GG genotype (adjusted odds ratio (OR2) = 0.27, 95 % CI = 0.125–0.611, P = 0.001), HSP 70 (+2437) CC genotype (OR2 = 0.17, 95 % CI = 0.0430.69, P = 0.013), while AG genotype of TNF β was found significantly associated with risk of NPC (OR2 = 1.97, 95 % CI = 1.019–3.83, P = 0.04). Analysis of environmental factors demonstrated association of alcohol consumption, living in mud houses and use of firewood for cooking as major risk factors for NPC. Individual haplotype association analysis showed significant risk associated with GTGA haplotype (OR = 68.61, 95 % CI = 2.47–190.37, P = 0.013) while a protective effect with CCAA and GCGA haplotypes (OR = 0.19, 95 % CI = 0.05–0.75, P = 0.019; OR = 0.01 95 % CI = 0.05–0.30, P = 0.007). The multi-analytical approaches applied in this study helped in identification of distinct gene-gene and gene-environment interactions significant in risk assessment of NPC.

Keywords

TNF HSP Nasopharyngeal cancer Northeast India Single nucleotide polymorphism 

Notes

Acknowledgments

This work was supported by Department of Biotechnology (Sanction Order No. & Date: BT/PR11126/Med/30/131/2008/03/2010). One of the authors (Meena Lakhanpal) thank the University Grants Commission, India (Ref. No: 20–1212009 (ai) EU-lV), for providing research fellowship.

Conflicts of interest

None

References

  1. 1.
    Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):421–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Chan AT, Teo PM, Johnson PJ. Nasopharyngeal carcinoma. Ann Oncol. 2002;13(7):1007–15.CrossRefPubMedGoogle Scholar
  3. 3.
    Kataki AC, Simons MJ, Das AK, Sharma K, Mehra NK. Nasopharyngeal carcinoma in the northeastern states of India. Chin J Cancer. 2011;30(2):106–13.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    ICMR Bulletin. Epidemiological and etiological factors associated with nasopharyngeal carcinoma. 2003; 33:9.Google Scholar
  5. 5.
    Jia WH, Qin HD. Non-viral environmental risk factors for nasopharyngeal carcinoma: a systematic review. Semin Cancer Biol. 2012;22(2):117–26.CrossRefPubMedGoogle Scholar
  6. 6.
    Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1765–77.CrossRefPubMedGoogle Scholar
  7. 7.
    Chan SH, Day NE, Kunaratnam N, Chia KB, Simons MJ. HLA and nasopharyngeal carcinoma in Chinese—a further study. Int J Cancer. 1983;32:171–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Jing J, Louie E, Henderson BE, Terasaki P. Histocompatibility leukocyte antigen patterns in nasopharyngeal carcinoma cases from California. Natl Cancer Inst Monogr. 1977;47:153–6.PubMedGoogle Scholar
  9. 9.
    Nazar-Stewart V, Vaughan TL, Burt RD, Chen C, Berwick M, Swanson GM. Glutathione S-transferase M1 and susceptibility to nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 1999;8(6):547–51.PubMedGoogle Scholar
  10. 10.
    Tiwawech D, Srivatanakul P, Karalak A, Ishida T. Glutathione S-transferase M1 gene polymorphism in Thai nasopharyngeal carcinoma. Asian Pac J Cancer Prev. 2005;6(3):270–5.PubMedGoogle Scholar
  11. 11.
    Cho EY, Hildesheim A, Chen CJ, et al. Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1 and hOGG1. Cancer Epidemiol Biomarkers Prev. 2003;12(10):1100–4.PubMedGoogle Scholar
  12. 12.
    Lakhanpal M, Singh LC, Rahman T, Sharma J, Singh MM, Kataki AC, et.al . Contribution of susceptibility locus at HLA class I region and environmental factors to occurrence of nasopharyngeal cancer in Northeast India. Tumour Biol. 2014.Google Scholar
  13. 13.
    Ooi EE, Ren EC, Chan SH. Association between microsatellites within the human MHC and nasopharyngeal carcinoma. Int J Cancer. 1997;74:229–32.CrossRefPubMedGoogle Scholar
  14. 14.
    Tracey KJ. TNF and Mae West or: death from too much of a good thing. Lancet. 1995;345:75–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Gadducci A, Ferdeghini M, Castellani C, Annicchiarico C, Gagetti O, Prontera C, et al. Serum levels of tumor necrosis factor (TNF), soluble receptors for TNF (55 and 75 kDa sTNFr), and soluble CD14 (sCD14) in epithelial ovarian cancer. Gynecol Oncology. 1995;58:184–8.CrossRefGoogle Scholar
  16. 16.
    Partanen R, Koskinen H, Hemminki K. Tumor necrosis factor-alpha (TNF-alpha) in patients who have asbestosis and develop cancer. Occup Environ Med. 1995;52:316–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med. 1996;334:1717–25.CrossRefPubMedGoogle Scholar
  18. 18.
    Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Palladino Jr MA, Shepard HM. Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science. 1985;230(4728):943–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Brenner DA, O'Hara M, Angel P, Chojkier M, Karin M. Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. Nature. 1989;337(6208):661–3.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhu Y, Xu Y, Wei Y, Liang W, Liao M, Zhang L. Association of IL-1B gene polymorphisms with nasopharyngeal carcinoma in a Chinese population. Clin Oncol (R Coll Radiol). 2008;20(3):207–11.CrossRefGoogle Scholar
  21. 21.
    Lakhanpal M, Yadav DS, Devi TR, Singh LC, Singh KJ, Latha SP, et al. Association of interleukin-1β −511 C/T polymorphism with tobacco-associated cancer in northeast India: a study on oral and gastric cancer. Cancer Gene. 2014;207(1–2):1–11.CrossRefGoogle Scholar
  22. 22.
    Salles G, Bienvenu J, Bastion Y, Barbier Y, Doche C, Warzocha K, et al. Elevated circulating levels of TNF- and its p55 soluble receptor are associated with an adverse prognosis in lymphoma patients. Br J Haematol. 1996;93:352–9.Google Scholar
  23. 23.
    Warzocha K, Salles G, Bienvenu J, Bastion Y, Dumontet C, Renard N, et al. Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients. J Clin Oncol. 1997;15:499–508.CrossRefPubMedGoogle Scholar
  24. 24.
    Tracey KJ, Wei H, Manogue KR, Fong Y, Hess DG, Nguyen HT, et al. Cachectin/tumor necrosis factor induces cachexia, anemia and inflammation. J Exp Med. 1988;167:1211–27.CrossRefPubMedGoogle Scholar
  25. 25.
    Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A. 1997;94:3195–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Messer G, Spengler U, Jung MC, Honold G, Blo¨mer K, Pape GR, et al. Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-b gene correlates with a variant amino acid in position 26 and reduced level of TNF-b production. J Exp Med. 1991;173:209–19.CrossRefPubMedGoogle Scholar
  27. 27.
    Stu¨ber F, Petersen M, Bokelmann F, Schade U. A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-a concentrations and outcome of patients with severe sepsis. Crit Care Med. 1996;24:381–4.CrossRefGoogle Scholar
  28. 28.
    Sargent CA, Dunham I, Trowsdale J, Campbell RD. Human major histocompatibility complex contains genes for the major heat shock protein HSP70. Proc Natl Acad Sci U S A. 1989;86:6.CrossRefGoogle Scholar
  29. 29.
    Milner CM, Campbell RD. Structure and expression of the MHC-linked HSP70 genes. Immunogenetics. 1990;32:242–51.CrossRefPubMedGoogle Scholar
  30. 30.
    Suto R, Srivastava PK. A mechanism for the specific immunogenicity of heat shock protein-chaperoned-peptides. Science. 1995;269:1585–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Soti C, Csermely P. Molecular chaperones in the etiology and therapy of cancer. Pathol Oncol Res. 1998;4:316–21.CrossRefPubMedGoogle Scholar
  32. 32.
    Guidelines for controlling and monitoring the tobacco epidemic. Geneva: World Health Organization. 1998Google Scholar
  33. 33.
    Diepstra A, Niens M, Vellenga E, et al. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin’s lymphoma. Lancet. 2005;1,365(9478):2216–24.CrossRefGoogle Scholar
  34. 34.
    Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22:1928–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Steinberg D, Colla P. CART—classification and regression trees. San Diego: Salford Systems; 1997.Google Scholar
  36. 36.
    Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001;69(1):138–47.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics. 2003;19(3):376–82.CrossRefPubMedGoogle Scholar
  38. 38.
    Pociot F, Briant L, Jongeneeel CV, Molvig J, Worsaae H, Abbal M, et al. Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-α and TNF-β by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus. Eur J Immunol. 1993;23:224–31.CrossRefPubMedGoogle Scholar
  39. 39.
    Nonomura N, Tokizane T, Nakayama M, Inoue H, Nishimura K, Muramatsu M, et al. Possible correlation between polymorphism in the tumor necrosis factor-beta gene and the clinicopathological features of bladder cancer in Japanese patients. Int J Urol. 2006;13(7):971–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Shimura T, Hagihara M, Takebe K, et al. The study of tumor necrosis factor beta gene polymorphism in lung cancer patients. Cancer. 1994;73:1184–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Shimura T, Hagihara M, Takebe K, et al. 10.5-kb homozygote of tumor necrosis factor-beta gene is associated with a better prognosis in gastric cancer patients. Cancer. 1995;75:1450–3.CrossRefPubMedGoogle Scholar
  42. 42.
    Azmy IA, Balasubramanian SP, Wilson AG, Stephenson TJ, Cox A, Brown NJ, et al. Role of tumor necrosis factor gene polymorphism (−308 and −238) in breast cancer susceptibility and severity. Breast Cancer Res. 2004;6:395–400.CrossRefGoogle Scholar
  43. 43.
    Park KS, Mok JW, Ko HE, Tokunaga K, Lee MH. Polymorphisms of tumour necrosis factors A and B in breast cancer. Eur J Immunogenet. 2002;29(1):7–10.CrossRefPubMedGoogle Scholar
  44. 44.
    Guo W, Wang N, Li Y, Zhang JH. Polymorphisms in tumor necrosis factor genes and susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high incidence region of North China. Chin Med J. 2005;118:1870–8.PubMedGoogle Scholar
  45. 45.
    Saito S, Kasai Y, Nomoto S, Fujiwara M, Akiyama S, Ito K, et al. Polymorphism of tumor necrosis factor in esophageal, gastric or colorectal carcinoma. Hepatogastroenterology. 2001;48:468–70.PubMedGoogle Scholar
  46. 46.
    Kamali-Sarvestani E, Gharesi-Fard B, Sarvari J, Talei AR. Association of TNF-α and TNF-β gene polymorphism with steroid receptor expression in breast cancer patients. Pathol Oncol Res. 2005;11:99–102.CrossRefPubMedGoogle Scholar
  47. 47.
    Milner CM, Campbell RD. Polymorphic analysis of the three MHC-linked HSP70 genes. Immunogenetics. 1992;36(6):357–62.CrossRefPubMedGoogle Scholar
  48. 48.
    Sfar S, Saad H, Mosbah F, Chouchane L. Association of HSP70-hom genetic variant with prostate cancer risk. Mol Biol Rep. 2008;35(3):459–64.CrossRefPubMedGoogle Scholar
  49. 49.
    Chouchane L, Ahmed SB, Baccouche S, Remadi S. Polymorphism in the tumor necrosis factor-alpha promotor region and in the heat shock protein 70 genes associated with malignant tumors. Cancer. 1997;80(8):1489–96.CrossRefPubMedGoogle Scholar
  50. 50.
    Wang Y, Zhou F, Wu Y, Xu D, Li W, Liang S. The relationship between three heat shock protein 70 gene polymorphisms and susceptibility to lung cancer. Clin Chem Lab Med. 2010;48(11):1657–63.CrossRefPubMedGoogle Scholar
  51. 51.
    Guo H, Deng Q, Wu C, Hu L, Wei S, Xu P, et al. Variations in HSPA1B at 6p21.3 are associated with lung cancer risk and prognosis in Chinese populations. Cancer Res. 2011;71(24):7576–86.CrossRefPubMedGoogle Scholar
  52. 52.
    Partida-Rodríguez O, Torres J, Flores-Luna L, Camorlinga M, Nieves-Ramírez M, Lazcano E, et al. Polymorphisms in TNF and HSP-70 show a significant association with gastric cancer and duodenal ulcer. Int J Cancer. 2010;126(8):1861–8.PubMedGoogle Scholar
  53. 53.
    Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, et al. HSP70 stimulates cytokine production through a CD14- dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med. 2000;6:435–42.CrossRefPubMedGoogle Scholar
  54. 54.
    Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, et al. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem. 2002;277:15028–34.CrossRefPubMedGoogle Scholar
  55. 55.
    Nam JM, McLaughlin JK, Blot WJ. Cigarette smoking, alcohol, and nasopharyngeal carcinoma: a case–control study among U.S. Whites. J Natl Cancer Inst. 1992;84(8):619–22.CrossRefPubMedGoogle Scholar
  56. 56.
    Ruan HL, Xu FH, Liu WS, et al. Alcohol and tea consumption in relation to the risk of nasopharyngeal carcinoma in Guangdong, China. Front Med China. 2010;4(4):448–56.CrossRefPubMedGoogle Scholar
  57. 57.
    Cheng YJ, Hildesheim A, Hsu MM, et al. Cigarette smoking, alcohol consumption and risk of nasopharyngeal carcinoma in Taiwan. Cancer Causes Control. 1999;10(3):201–7.CrossRefPubMedGoogle Scholar
  58. 58.
    Brooks PJ, Theruvathu JA. DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol. 2005;35(3):187–93.CrossRefPubMedGoogle Scholar
  59. 59.
    Yu HS, Oyama T, Isse T, et al. Formation of acetaldehyde-derived DNA adducts due to alcohol exposure. Chem Biol Interact. 2010;188(3):367–75.CrossRefPubMedGoogle Scholar
  60. 60.
    Giovannucci E, Stampfer MJ, Colditz GA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst. 1993;85(11):875–84.CrossRefPubMedGoogle Scholar
  61. 61.
    Seitz HK, Stickel F. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biol Chem. 2006;387(4):349–60.CrossRefPubMedGoogle Scholar
  62. 62.
    Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology. 2001;12(4):420–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Vasdev S, Wadhawan S, Ford CA, Parai S, Longerich L, Gadag V. Dietary vitamin B6 supplementation prevents ethanolinduced hypertension in rats. Nutr Metab Cardiovasc Dis. 1999;9(2):55–63.PubMedGoogle Scholar
  64. 64.
    Yu MC, Ho JH, Ross RK, Henderson BE. Nasopharyngeal carcinoma in Chinese salted fish or inhaled smoke? Prev Med. 1981;10(1):15–24.CrossRefPubMedGoogle Scholar
  65. 65.
    Guo X, Johnson RC, Deng H, et al. Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China. Int J Cancer. 2009;124(12):2942–7.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Zheng YM, Tuppin P, Hubert A, et al. Environmental and dietary risk factors for nasopharyngeal carcinoma: a case–control study in Zangwu County, Guangxi, China. Br J Cancer. 1994;69(3):508–14.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Meena Lakhanpal
    • 1
  • Laishram Chandreshwor Singh
    • 1
  • Tashnin Rahman
    • 2
  • Jagnnath Sharma
    • 2
  • M. Madhumangal Singh
    • 3
  • Amal Chandra Kataki
    • 2
  • Saurabh Verma
    • 1
  • Santhi Latha Pandrangi
    • 1
  • Y. Mohan Singh
    • 3
  • Saima Wajid
    • 4
  • Sujala Kapur
    • 1
  • Sunita Saxena
    • 1
  1. 1.National Institute of Pathology, Safdarjang Hospital CampusIndian Council of Medical ResearchNew DelhiIndia
  2. 2.Dr. B. Barooah Cancer InstituteGuwahatiIndia
  3. 3.Regional Institute of Medical ScienceImphalIndia
  4. 4.Department of BiotechnologyNew DelhiIndia

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