title: Contribution of susceptibility locus at HLA class I region and environmental factors to occurrence of nasopharyngeal cancer in Northeast India.
abstract: High incidence of nasopharyngeal carcinoma (NPC) has been reported from China, Southeast Asia and Northeast (NE) region of India. Populations at geographic regions having higher incidence of NPC display human leukocyte antigen (HLA) distribution patterns different from areas having low incidence. The current study has investigated the contribution of environmental risk factors and ethnic variation of microsatellite markers in HLA region for the high incidence of NPC in NE India. Genotyping of HLA region using 33 microsatellite markers by fragment length analysis was done in 220 study subjects (120 NPC patients and 100 healthy controls). Association analysis showed two adjacent microsatellite markers HL003 (allele 121) and D6S2704 (allele 218) in the HLA class I region having association with high risk of NPC while allele 127 of HL003 and allele 255 of D6S2678 conferred a protective effect. The environmental factors mainly use of firewood (odds ratio (OR) = 3.797385, confidence interval (CI) = 1.97-7.30, P < 0), living in mud house (OR = 3.46, CI = 1.19-10.08, P = 0.022) and consumption of alcohol (OR = 2.11, CI = 1.02-4.37, P = 0.043) were found as major risk factors for NPC. Higher-order interaction showed combination of smoked food consumption and firewood use for cooking in multifactor dimensionality reduction (MDR) analysis and interaction of non-firewood users, non-ventilated houses and residence in mud houses in classification and regression tree (CART) analysis as the significant risk factors for NPC. Expression of Epstein-Barr virus (EBV) RNA was found in 92% (23/25) of NPC cases suggesting its significant role in NPC aetiopathogenesis. This study identified association of NPC with a susceptibility locus in the HLA class I region which has complex interaction with viral DNA and environmental factors.
authors.affiliation: Safdarjang Hospital Campus, Indian Council of Medical Research, National Institute of Pathology, New Delhi, 110029, India.
authors.forename: Meena
authors.initials: M
authors.lastname: Lakhanpal
authors.forename: Laishram Chandreshwor
authors.initials: LC
authors.lastname: Singh
authors.forename: Tashnin
authors.initials: T
authors.lastname: Rahman
authors.forename: Jagnnath
authors.initials: J
authors.lastname: Sharma
authors.forename: M Madhumangal
authors.initials: MM
authors.lastname: Singh
authors.forename: Amal Chandra
authors.initials: AC
authors.lastname: Kataki
authors.forename: Saurabh
authors.initials: S
authors.lastname: Verma
authors.forename: Pradeep Singh
authors.initials: PS
authors.lastname: Chauhan
authors.forename: Y Mohan
authors.initials: YM
authors.lastname: Singh
authors.forename: Saima
authors.initials: S
authors.lastname: Wajid
authors.forename: Sujala
authors.initials: S
authors.lastname: Kapur
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D007194:India; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D012307:Risk Factors
chemical_list: D006680:HLA Antigens