Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.12.4927

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

Lourembam, Deepak Singh (Department of Biotechnology, Manipur University)
Singh, Asem Robinson (Department of Biotechnology, Manipur University)
Sharma, T. Dhaneshor (Department of Radiotherapy, Regional Institute of Medical Sciences)
Singh, Th Sudheeranjan (Department of Otorhinolaryngology, Regional Institute of Medical Sciences)
Singh, Thiyam Ramsing (Department of Biotechnology, Manipur University)
Singh, Lisam Shanjukumar (Department of Biotechnology, Manipur University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.12, 2015 , pp. 4927-4935 More about this Journal
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
Nasopharyngeal carcinoma; epstein-barr virus; viral load; genetic polymorphism; risk factor;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
연도 인용수 순위
1 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.   DOI
2 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.   DOI
3 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.   DOI
4 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.
5 Kataki AC, Simons MJ, Das AK, et al (2011). Nasopharyngeal carcinoma in the Northeastern states of India. Chin J Cancer, 30, 106-13.   DOI
6 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].
7 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.   DOI
8 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.   DOI
9 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.   DOI
10 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.   DOI
11 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.
12 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.
13 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.   DOI
14 Mathur S (2003). Epidemiological and etiological factors associated with nasopharyngeal carcinoma. ICMR Bulletin. Indian Press New Delhi, 33.
15 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.   DOI
16 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.   DOI   ScienceOn
17 Nguyen QM, Nguyen HC, Parkin DM (1998). Cancer incidence in Ho Chi Minh City, Viet Nam, 1995-1996. Int J Cancer, 76, 472-9.   DOI
18 Parkin D, Whelan S, Ferlay J, et al (2002). Cancer incidence in five continents Vol. VIII. IARC scientific publications, 155.
19 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.   DOI
20 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.   DOI   ScienceOn
21 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.   DOI
22 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.   DOI
23 Saiki RK, Gelfand DH, Stoffel S, et al (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science, 239, 487-91.   DOI
24 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.
25 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.
26 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.
27 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.   DOI
28 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.   DOI
29 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.   DOI
30 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.   DOI
31 Tiwawech D, Srivatanakul P, Karalak A, et al (2006). Cytochrome P450 2A6 polymorphism in nasopharyngeal carcinoma. Cancer Lett, 241, 135-41.   DOI
32 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.   DOI
33 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.
34 Tsao SW, Tsang CM, To KF, et al (2015). The role of Epstein-Barr virus in epithelial malignancies. J Pathol, 235, 323-33.   DOI
35 Yang J, Li L, Yin X, et al (2015). The association between gene polymorphisms and risk of nasopharyngeal carcinoma. Med Oncol, 32, 398.   DOI
36 Tsao SW, Yip YL, Tsang CM, et al (2014). Etiological factors of nasopharyngeal carcinoma. Oral Oncol, 50, 330-8.   DOI
37 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.   DOI
38 Wei Y, Zhou T, Lin H, et al (2013). Significant associations between GSTM1/GSTT1 polymorphisms and nasopharyngeal cancer risk. Tumour Biol, 34, 887-94.   DOI
39 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.   DOI
40 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.   DOI
41 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.   DOI
42 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.   DOI
43 Bhatia P, Singh L (1981). Evaluation of contrast radiography in nasopharyngeal malignancy. Indian J Cancer, 18, 141.
44 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.
45 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.
46 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.   DOI
47 Chang ET, Adami HO (2006). The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 1765-77.   DOI
48 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.   DOI
49 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.
50 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.   DOI
51 Go RE, Hwang KA, Choi KC (2015). Cytochrome P450 1 family and cancers. J Steroid Biochem Mol Biol, 147, 24-30.   DOI
52 Guengerich FP, Shimada T (1991). Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol, 4, 391-407.   DOI
53 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.   DOI
54 Ho HC (1976). Epidemiology of nasopharyngeal carcinoma. Gann Monograph Cancer Res, 18, 49-61.
55 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.   DOI
56 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.   DOI