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.

Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population

“…This inconsistency may be due to differences in study populations, NPC subtypes, or definitions of lifestyle behaviors. A significant association between alcohol intake and NPC risk was observed in this study and other research [39][40][41], while several studies have observed a lack of association between alcohol and NPC risk [10,42,43]. We also observed that betel nut chewing was significantly associated with NPC risk.…”

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

“…Several reports have shown that different HLA products and genes may act as either significant risk or protective factors for NPC [12,13]. The HLA-linked TNF and HSP 70 genes are of particular interest because of their involvement in tumour immunity and immune pathogenesis which makes them potential cancer susceptibility candidates.…”

“…Among the various genetic factors reported, only human leukocyte antigen (HLA) present at chromosome 6 had shown strong association with NPC and had also been linked to outcomes of NPC. Studies have shown that many HLA class I and II alleles and other candidate genes which lie within or nearby the HLA may have some role in NPC susceptibility [12,13]. The HLA-linked TNF-α and heat shock protein 70 (HSP 70) genes are of particular interest because of their involvement in tumour immunity and cancer biology [14][15][16].…”

HLA-A*26-A*30 and HLA-DRB1*10 could be predictors of nasopharyngeal carcinoma risk in high-risk Tunisian families

“…Nasopharyngeal carcinoma (NPC) carcinogenesis involves an interplay of genetic and environmental factors and the Epstein-Barr virus (1). Existing evidence confirms an association between human leukocyte antigen (HLA) profile and NPC, and several alleles and haplotypes are associated with NPC risk (2,3). We previously reported an association between a specific HLA profile and sporadic NPC in north Tunisia (4).…”

“…Nehla Mokni-Baizig 1) , Yosr Gorgi 2) , Mohamed Elghourabi 3) , Mouna Makhlouf 2) , Hamouda Boussen 1) , Said Gritli 4) , Michèle Elmay 5) , Amor Gamoudi 1) , and Ahmed Elmay 1) attributable to one mechanism or perhaps a combination of mechanisms. However, more extensive investigations, probably including HLA family studies, are required in order to clarify this issue.…”