title: Study of single nucleotide polymorphisms of tumour necrosis factors and HSP genes in nasopharyngeal carcinoma in North East India.
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.
authors.affiliation: National Institute of Pathology, Safdarjang Hospital Campus, Indian Council of Medical Research, New Delhi, 110029, India.
authors.forename: Meena
authors.initials: M
authors.lastname: Lakhanpal
authors.affiliation: National Institute of Pathology, Safdarjang Hospital Campus, Indian Council of Medical Research, New Delhi, 110029, India.
authors.forename: Laishram Chandreshwor
authors.initials: LC
authors.lastname: Singh
authors.affiliation: Dr. B. Barooah Cancer Institute, Guwahati, 781 016, Assam, India.
authors.forename: Tashnin
authors.initials: T
authors.lastname: Rahman
authors.affiliation: Dr. B. Barooah Cancer Institute, Guwahati, 781 016, Assam, India.
authors.forename: Jagnnath
authors.initials: J
authors.lastname: Sharma
authors.affiliation: Regional Institute of Medical Science, Imphal, 795004, Manipur, India.
authors.forename: M Madhumangal
authors.initials: MM
authors.lastname: Singh
authors.affiliation: Dr. B. Barooah Cancer Institute, Guwahati, 781 016, Assam, India.
authors.forename: Amal Chandra
authors.initials: AC
authors.lastname: Kataki
authors.affiliation: National Institute of Pathology, Safdarjang Hospital Campus, Indian Council of Medical Research, New Delhi, 110029, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Verma
authors.affiliation: National Institute of Pathology, Safdarjang Hospital Campus, Indian Council of Medical Research, New Delhi, 110029, India.
authors.forename: Santhi Latha
authors.initials: SL
authors.lastname: Pandrangi
authors.affiliation: Regional Institute of Medical Science, Imphal, 795004, Manipur, India.
authors.forename: Y Mohan
authors.initials: YM
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, Jamia Hamdard, New Delhi, 110062, India.
authors.forename: Saima
authors.initials: S
authors.lastname: Wajid
authors.affiliation: National Institute of Pathology, Safdarjang Hospital Campus, Indian Council of Medical Research, New Delhi, 110029, India.
authors.forename: Sujala
authors.initials: S
authors.lastname: Kapur
authors.affiliation: National Institute of Pathology, Safdarjang Hospital Campus, Indian Council of Medical Research, New Delhi, 110029, India. sunita_saxena@yahoo.com.
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D016022:Case-Control Studies; D002648:Child; D004777:Environment; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: HSP; Nasopharyngeal cancer; Northeast India; Single nucleotide polymorphism; TNF