Dysfunction of mitochondria due to environmental carcinogens in nasopharyngeal carcinoma in the ethnic group of Northeast Indian population

Nasopharyngeal carcinoma (NPC) is a rare cancer worldwide, but in India, NPC is uncommon in its subcontinent except in the north-eastern part of the country. NPC is thought to be caused by the combined effects of environmental carcinogens, genetic susceptibility and Epstein-Barr virus (EBV). This is the first study that aimed to examine the selected risk factors, mostly dietary, viral environmental, metabolic gene polymorphisms, mitochondrial DNA (mtDNA) copy number variation and their risk, in subjects who are highly prone to NPC in the ethnic groups of Northeast India, which has included cases, first-degree relatives and controls. The cases and controls were selected from three ethnic groups (Manipuri, Naga and Mizo) of Northeast India with high prevalence of NPC. This case–control family study includes 64 NPC patients, 88 first-degree relatives and 100 controls having no history of cancer. PCR-based detection was done for EBV–latent membrane protein 1 (LMP1) gene and glutathione S-transferase Mu 1 (GSTM1)–glutathione S-transferase theta 1 (GSTT1) polymorphism. A comparative ΔCt method was used for the determination of mtDNA content. An increased risk of 2.00–6.06-folds to NPC was observed with those who intake smoked meat and fish, salted fish and fermented fish; betel nut chewers; tobacco smokers; alcohol drinkers; and those who have kitchen inside the living room, glutathione S-transferase null genotype and EBV infection. The risk of NPC increased in cases with decreased mtDNA copy number (P _trend = 0.007). A significant difference between GST null genotypes and EBV infection with mtDNA content was found in the cases (P < 0.0001). The understandings of environment–genetic risk factors and their role in the etiology of NPC are helpful as preventive measures and screening.