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Evaluation of Risk Factors for Nasopharyngeal Carcinoma in a High-risk Area of India, the Northeastern Region

  • Published : 2015.07.13

Abstract

Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of the country has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted to identify the potential risk factors for NPC development in this region. Information was collected by interviewer about socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupational history, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real time PCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6 polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay. Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001). Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III and IV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzyme activity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke, living in poorly ventilated house and alcohol consumption were associated with NPC development among the population of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphism of CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living in poorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region of India. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measures and screening.

Keywords

References

  1. Adham M, Greijer AE, Verkuijlen SA, et al (2013). Epstein-barr virus DNA load in nasopharyngeal brushings and whole blood in nasopharyngeal carcinoma patients before and after treatment. Clin Cancer Res, 19, 2175-86. https://doi.org/10.1158/1078-0432.CCR-12-2897
  2. Arand M, Muhlbauer R, Hengstler J, et al (1996). A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal Biochem, 236, 184-6. https://doi.org/10.1006/abio.1996.0153
  3. Ariyoshi N, Takahashi Y, Miyamoto M, et al (2000). Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C. Pharmacogenetics, 10, 687-93. https://doi.org/10.1097/00008571-200011000-00003
  4. Bhatia P, Singh L (1981). Evaluation of contrast radiography in nasopharyngeal malignancy. Indian J Cancer, 18, 141.
  5. Boccia S, Cadoni G, Sayed-Tabatabaei FA, et al (2008). CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer. J Cancer Res Clin Oncol, 134, 93-100.
  6. Bozina N, Bradamante V, Lovric M (2009). Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol, 60, 217-42.
  7. Burt RD, Vaughan TL, McKnight B (1992). Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the United States. Int J Cancer, 52, 549-56. https://doi.org/10.1002/ijc.2910520409
  8. Chang ET, Adami HO (2006). The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 1765-77. https://doi.org/10.1158/1055-9965.EPI-06-0353
  9. Cheng YJ, Chien YC, Hildesheim A, et al (2003). No association between genetic polymorphisms of CYP1A1, GSTM1, GSTT1, GSTP1, NAT2, and nasopharyngeal carcinoma in Taiwan. Cancer Epidemiol Biomarkers Prev, 12, 179-80.
  10. Gattas GJ, de Carvalho MB, Siraque MS, et al (2006). Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer. Head Neck, 28, 819-26. https://doi.org/10.1002/hed.20410
  11. Ghosh SK, Singh AS, Mondal R, et al (2014). Dysfunction of mitochondria due to environmental carcinogens in nasopharyngeal carcinoma in the ethnic group of Northeast Indian population. Tumour Biol, 35, 6715-24. https://doi.org/10.1007/s13277-014-1897-x
  12. Go RE, Hwang KA, Choi KC (2015). Cytochrome P450 1 family and cancers. J Steroid Biochem Mol Biol, 147, 24-30. https://doi.org/10.1016/j.jsbmb.2014.11.003
  13. Guengerich FP, Shimada T (1991). Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol, 4, 391-407. https://doi.org/10.1021/tx00022a001
  14. Hayashi S, Watanabe J, Kawajiri K (1991). Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem, 110, 559-65. https://doi.org/10.1093/oxfordjournals.jbchem.a123619
  15. Ho HC (1976). Epidemiology of nasopharyngeal carcinoma. Gann Monograph Cancer Res, 18, 49-61.
  16. Huang FM, Chen HC, Khan MA, et al (2013). CYP2A6, CYP1A1, and CYP2D6 polymorphisms in lung cancer patients from central south China. Med Oncol, 30, 521. https://doi.org/10.1007/s12032-013-0521-z
  17. Hussein AG, Pasha HF, El-Shahat HM, et al (2014). CYP1A1 gene polymorphisms and smoking status as modifier factors for lung cancer risk. Gene, 541, 26-30. https://doi.org/10.1016/j.gene.2014.03.003
  18. Islam MS, Ahmed MU, Sayeed MS, et al (2013). Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population. Clin Chim Acta, 416, 11-9. https://doi.org/10.1016/j.cca.2012.11.011
  19. Ji MF, Huang QH, Yu X, et al (2014). Evaluation of plasma Epstein-Barr virus DNA load to distinguish nasopharyngeal carcinoma patients from healthy high-risk populations in Southern China. Cancer, 120, 1353-60. https://doi.org/10.1002/cncr.28564
  20. Jiang XY, Chang FH, Bai TY, et al (2014). Susceptibility of lung cancer with polymorphisms of CYP1A1, GSTM1, GSTM3, GSTT1 and GSTP1 genotypes in the population of Inner Mongolia region. Asian Pac J Cancer Prev, 15, 5207-14. https://doi.org/10.7314/APJCP.2014.15.13.5207
  21. Jiang Y, Li N, Dong P, et al (2011). Polymorphisms in GSTM1, GSTTI and GSTP1 and nasopharyngeal cancer in the east of China: a case-control study. Asian Pac J Cancer Prev, 12, 3097-100.
  22. Kataki AC, Simons MJ, Das AK, et al (2011). Nasopharyngeal carcinoma in the Northeastern states of India. Chin J Cancer, 30, 106-13. https://doi.org/10.5732/cjc.010.10607
  23. Lakhanpal M, Singh LC, Rahman T, et al (2014). Contribution of susceptibility locus at HLA class I region and environmental factors to occurrence of nasopharyngeal cancer in Northeast India. Tumour Biol, [DETAIL].
  24. Lin JC, Chen KY, Wang WY, et al (2001). Detection of Epstein-Barr virus DNA in the peripheral-blood cells of patients with nasopharyngeal carcinoma: relationship to distant metastasis and survival. J Clin Oncol, 19, 2607-15. https://doi.org/10.1200/JCO.2001.19.10.2607
  25. Lin JC, Wang WY, Chen KY, et al (2004). Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med, 350, 2461-70. https://doi.org/10.1056/NEJMoa032260
  26. Liu YL, Xu Y, Li F, et al (2013a). CYP2A6 deletion polymorphism is associated with decreased susceptibility of lung cancer in Asian smokers: a meta-analysis. Tumour Biol, 34, 2651-7. https://doi.org/10.1007/s13277-013-0815-y
  27. Liu ZB, Shu J, Wang LP, et al (2013b). Cytochrome P450 2A6 deletion polymorphism and risk of lung cancer: a meta-analysis. Mol Biol Rep, 40, 5255-9. https://doi.org/10.1007/s11033-013-2625-0
  28. Lo YM, Chan LY, Lo KW, et al (1999). Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res, 59, 1188-91.
  29. Lo YM, Leung SF, Chan LY, et al (2000). Plasma cell-free Epstein-Barr virus DNA quantitation in patients with nasopharyngeal carcinoma. Correlation with clinical staging. Ann NY Acad Sci, 906, 99-101.
  30. Lung ML, Cheung AK, Ko JM, et al (2014). The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma. Chin J Cancer, 33, 556-68. https://doi.org/10.5732/cjc.014.10170
  31. Mathur S (2003). Epidemiological and etiological factors associated with nasopharyngeal carcinoma. ICMR Bulletin. Indian Press New Delhi, 33.
  32. Moraes LN, Borges MF, Sousa PA, et al (2012). Lack of association of CYP1A1-MspI SNP and GSTM1 null genotypes with cancer in a Brazilian family with unusually high cancer incidence. Genet Mol Res, 11, 1610-7. https://doi.org/10.4238/2012.June.15.10
  33. Murthy AK, Kumar V, Suresh KP (2013). Meta-analysis of GSTM1 and GSTT1 polymorphisms and risk of nasopharyngeal cancer. Asian Pac J Cancer Prev, 14, 1697-701. https://doi.org/10.7314/APJCP.2013.14.3.1697
  34. Nguyen QM, Nguyen HC, Parkin DM (1998). Cancer incidence in Ho Chi Minh City, Viet Nam, 1995-1996. Int J Cancer, 76, 472-9. https://doi.org/10.1002/(SICI)1097-0215(19980518)76:4<472::AID-IJC5>3.0.CO;2-O
  35. Nonoyama M, Pagano JS (1973). Homology between Epstein-Barr virus DNA and viral DNA from Burkitt's lymphoma and nasopharyngeal carcinoma determined by DNA-DNA reassociation kinetics. Nature, 242, 44-7. https://doi.org/10.1038/242044a0
  36. Nor Hashim NA, Ramzi NH, Velapasamy S, et al (2012). Identification of genetic and non-genetic risk factors for nasopharyngeal carcinoma in a Southeast Asian population. Asian Pac J Cancer Prev, 13, 6005-10. https://doi.org/10.7314/APJCP.2012.13.12.6005
  37. Parkin D, Whelan S, Ferlay J, et al (2002). Cancer incidence in five continents Vol. VIII. IARC scientific publications, 155.
  38. Rossini A, Rapozo DC, Soares Lima SC, et al (2007). Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a western population. Carcinogenesis, 28, 2537-42. https://doi.org/10.1093/carcin/bgm222
  39. Russo A, Francelin PR, Galbiatti AL, et al (2013). Association between GSTP1, GSTM1 and GSTT1 polymorphisms involved in xenobiotic metabolism and head and neck cancer development. Mol Biol Rep, 40, 4181-8. https://doi.org/10.1007/s11033-013-2499-1
  40. Saiki RK, Gelfand DH, Stoffel S, et al (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science, 239, 487-91. https://doi.org/10.1126/science.2448875
  41. Sharma TD, Singh TT, Laishram RS, et al (2011). Nasopharyngeal carcinoma--a clinico-pathological study in a regional cancer centre of northeastern India. Asian Pac J Cancer Prev, 12, 1583-7.
  42. Shotelersuk K, Khorprasert C, Sakdikul S, et al (2000). Epstein-Barr virus DNA in serum/plasma as a tumor marker for nasopharyngeal cancer. Clin Cancer Res, 6, 1046-51.
  43. Song DK, Xing DL, Zhang LR, et al (2009). Association of NAT2, GSTM1, GSTT1, CYP2A6, and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China. Cancer Detect Prev, 32, 416-23. https://doi.org/10.1016/j.cdp.2009.02.003
  44. Stevens SJ, Pronk I, Middeldorp JM (2001a). Toward standardization of Epstein-Barr virus DNA load monitoring: unfractionated whole blood as preferred clinical specimen. J Clin Microbiol, 39, 1211-6. https://doi.org/10.1128/JCM.39.4.1211-1216.2001
  45. Stevens SJ, Verschuuren EA, Pronk I, et al (2001b). Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood, 97, 1165-71. https://doi.org/10.1182/blood.V97.5.1165
  46. Stevens SJ, Vervoort MB, van den Brule AJ, et al (1999). Monitoring of epstein-barr virus DNA load in peripheral blood by quantitative competitive PCR. J Clin Microbiol, 37, 2852-7.
  47. Tamaki Y, Arai T, Sugimura H, et al (2011). Association between cancer risk and drug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan. Drug Metab Pharmacokinet, 26, 516-22. https://doi.org/10.2133/dmpk.DMPK-11-RG-046
  48. Tiwawech D, Srivatanakul P, Karalak A, et al (2006). Cytochrome P450 2A6 polymorphism in nasopharyngeal carcinoma. Cancer Lett, 241, 135-41. https://doi.org/10.1016/j.canlet.2005.10.026
  49. Topcu Z, Chiba I, Fujieda M, et al (2002). CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka. Carcinogenesis, 23, 595-8. https://doi.org/10.1093/carcin/23.4.595
  50. Tsang CM, Deng W, Yip YL, et al (2014). Epstein-Barr virus infection and persistence in nasopharyngeal epithelial cells. Chin J Cancer, 33, 549-55.
  51. Tsao SW, Tsang CM, To KF, et al (2015). The role of Epstein-Barr virus in epithelial malignancies. J Pathol, 235, 323-33. https://doi.org/10.1002/path.4448
  52. Tsao SW, Yip YL, Tsang CM, et al (2014). Etiological factors of nasopharyngeal carcinoma. Oral Oncol, 50, 330-8. https://doi.org/10.1016/j.oraloncology.2014.02.006
  53. Tune CE, Liavaag PG, Freeman JL, et al (1999). Nasopharyngeal brush biopsies and detection of nasopharyngeal cancer in a high-risk population. J Natl Cancer Inst, 91, 796-800. https://doi.org/10.1093/jnci/91.9.796
  54. Wei Y, Zhou T, Lin H, et al (2013). Significant associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer risk. Tumour Biol, 34, 887-94. https://doi.org/10.1007/s13277-012-0623-9
  55. Yang J, Li L, Yin X, et al (2015). The association between gene polymorphisms and risk of nasopharyngeal carcinoma. Med Oncol, 32, 398. https://doi.org/10.1007/s12032-014-0398-5
  56. Yip TT, Ngan RK, Fong AH, et al (2014). Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol, 50, 527-38. https://doi.org/10.1016/j.oraloncology.2013.12.011

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