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A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India

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Tumor Biology

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.

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Abbreviations

OSCC:

Oral squamous cell carcinoma

Indels:

Short insertion and deletions

SNP:

Single nucleotide polymorphism

NGS:

Next generation sequencing

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Acknowledgments

The authors would like to thank Genotypic Technology (P) Ltd., Bangalore. The authors would also like to thank the Indian Council of Medical Research for their financial support.

Conflicts of interest

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Authors and Affiliations

  1. National Institute of Pathology, Indian Council of Medical Research, Room No 206, Safdarjung Hospital Campus, New Delhi, 110029, India

    Dhirendra Singh Yadav, Anand Verma, Thoudam Regina Devi, L. C. Singh, Sunita Saxena & Sujala Kapur

  2. Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, 610101, Tamil Nadu, India

    Indranil Chattopadhyay

  3. Dr B. Borooah Cancer Institute, Guwahati, 786001, Assam, India

    Jagannath Dev Sharma & Amal Ch. Kataki

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  1. Dhirendra Singh Yadav
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  2. Indranil Chattopadhyay
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Correspondence to Sujala Kapur.

Additional information

Dhirendra Singh Yadav and Indranil Chattopadhyay have equal contribution to this study.

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Yadav, D.S., Chattopadhyay, I., Verma, A. et al. A pilot study evaluating genetic alterations that drive tobacco- and betel quid-associated oral cancer in Northeast India. Tumor Biol. 35, 9317–9330 (2014). https://doi.org/10.1007/s13277-014-2222-4

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  • DOI: https://doi.org/10.1007/s13277-014-2222-4

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