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

Abstract

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.

Role of the TGFβ/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis

“…As a disease that arises from the epithelial lining of the nasopharynx, NPC has a multifactorial etiology that includes genetic factors as well as smoking and alcohol consumption [3, 4]. Radiotherapy has become the standard radical treatment for patients with NPC, with reported long-term effects [5].…”

Association Between Alcohol Consumption and Risk of Nasopharyngeal Carcinoma: A Comprehensive Meta‐Analysis of Epidemiological Studies

“…The characteristics of the included studies are in Tables and . A total of 23 case–control studies (Ban et al., ; Chen et al., ; Cheng et al., ; Ekburanawat et al., ; Fachiroh et al., ; Ghosh et al., ; Ji et al., ; Khlifi et al., ; Lakhanpal et al., ; Lo et al., ; Lye et al., ; Mabuchi et al., ; Nong et al., ; Polesel et al., ; Shanmugaratnam et al., ; Sriamporn et al., ; Wei et al., ; Yang et al., ; Yong et al., ; Yuan et al., ; Zhang et al., ; Zou et al., , ) and 2 cohort studies (Friborg et al., ; Li et al., ) were included in the overall meta‐analysis. The other 5 studies (Nam et al., ; Ruan et al., ; Vaughan, ; Vaughan et al., ; Yu et al., ) did not include information on ever drinkers versus nondrinkers, so they were used only in the subgroup analysis of drinking‐related characteristics associated with NPC risk.…”

Influence of the CYP1A1 T3801C Polymorphism on Tobacco and Alcohol-Associated Head and Neck Cancer Susceptibility in Northeast India

“…Epidemiological studies from the northeast India reported tobacco smoking as one of the strongest risk factor for HNC (Yadav et al, 2010;Talukdar et al, 2013;Choudhury and Ghosh, 2014;Ghosh et al, 2014a) . Moreover, it was seen that tobacco-betel quid chewing also had a very high impact on HNC risk (Sharan et al, 2012;Choudhury et al, 2014) .…”

“…Tobacco in any form generates free radicals that deplete antioxidants and cause oxidative damage to DNA, proteins and lipids resulting in cancers. Similarly; alcohol consumption is linked to an increase in risk of HNC (Bektas-Kayhan et al, 2014;Ghosh et al, 2014a;Krishna et al, 2014). Recent studies have revealed mutagenic effects of alcohol on human chromosomes in vitro (Hsu et al, 1991).…”