title: A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India.
abstract: The susceptibility of an individual to oral cancer is mediated by genetic factors and carcinogen-exposure behaviors such as betel quid chewing, tobacco use, and alcohol consumption. This pilot study was aimed to identify the genetic alteration in 100 bp upstream and downstream flanking regions in addition to the exonic regions of 169 cancer-associated genes by using Next Generation sequencing with aim to elucidate the molecular pathogenesis of tobacco- and betel quid-associated oral cancer of Northeast India. To understand the role of chemical compounds present in tobacco and betel quid associated with the progression of oral cancer, single nucleotide polymorphisms (SNPs) and insertion and deletion (Indels) found in this study were analyzed for their association with chemical compounds found in tobacco and betel quid using Comparative Toxogenomic Database. Genes (AR, BRCA1, IL8, and TP53) with novel SNP were found to be associated with arecoline which is the major component of areca nut. Genes (BARD1, BRCA2, CCND2, IGF1R, MSH6, and RASSF1) with novel deletion and genes (APC, BRMS1, CDK2AP1, CDKN2B, GAS1, IGF1R, and RB1) with novel insertion were found to be associated with aflatoxin B1 which is produced by fermented areca nut. Genes (ADH6, APC, AR, BARD1, BRMS1, CDKN1A, E2F1, FGFR4, FLNC, HRAS, IGF1R, IL12B, IL8, NBL1, STAT5B, and TP53) with novel SNP were found to be associated with aflatoxin B1. Genes (ATM, BRCA1, CDKN1A, EGFR, IL8, and TP53) with novel SNP were found to be associated with tobacco specific nitrosamines.
authors.affiliation: National Institute of Pathology, Indian Council of Medical Research, Room No 206, Safdarjung Hospital Campus, New Delhi, 110029, India, dsyadav12@gmail.com.
authors.forename: Dhirendra Singh
authors.initials: DS
authors.lastname: Yadav
authors.forename: Indranil
authors.initials: I
authors.lastname: Chattopadhyay
authors.forename: Anand
authors.initials: A
authors.lastname: Verma
authors.forename: Thoudam Regina
authors.initials: TR
authors.lastname: Devi
authors.forename: L C
authors.initials: LC
authors.lastname: Singh
authors.forename: Jagannath Dev
authors.initials: JD
authors.lastname: Sharma
authors.forename: Amal Ch
authors.initials: ACh
authors.lastname: Kataki
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
authors.forename: Sujala
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000506:poisoning; D000368:Aged; D001114:Areca / Q000009:adverse effects* / Q000737:chemistry; D001115:Arecoline / Q000506:poisoning; D002874:Chromosome Mapping; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D004273:DNA, Neoplasm; D001115:Arecoline; D016604:Aflatoxin B1