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Gene polymorphisms and oral cancer risk in tobacco habitués

  • Original Article
  • Published:
Tumor Biology

Abstract

Oral cancer incidence of 77,003 poses a major health concern in India, with 5–10 % tobacco habitués developing oral cancer. The current study examined the role of specific genomic variants in oral cancer. We examined five genomic variants represented as single nucleotide polymorphisms (SNPs) in genes associated with cell proliferation and cellular invasion. The SNPs rs2124437 (RASGRP3), rs1335022 (GRIK2), rs4512367 (PREX2), rs4748011 (CCDC3), and rs1435218 (LNX1) were analyzed in 500 histopathologically confirmed oral cancers and 500 healthy controls with a minimum of 10 years of tobacco usage. Allelic discrimination real-time PCR SYBR Green assay was used. The genotypic and allelic frequencies between cases and controls were analyzed using SPSS software (version 19) and odds ratio (OR) using Hutchon.net, indicating increased risk to oral cancers. A significant association of the SNPs in oral cancer was observed in RASGRP3 AA (rs2124437) (p < 0.000, OR 1.34, 95 % confidence interval (CI) 1.01–1.76), GRIK2 TT (rs1335022) (p = 0.008, OR 1.58, 95 % CI 1.23–2.03), PREX2 CC (p = 0.008, OR 1.56, 95 % CI 1.15–2.1), and TT (p < 0.000, OR 2.77, 1.68–4.57) genotypes, whereas the heterozygous genotypes showed higher frequencies in controls, i.e., GRIK2 CT (rs1335022) (p = 0.029, OR 0.68, 95 % CI 0.53–0.87) and PREX2 CT (p = 0.004, OR 0.49, 95 % CI 0.37–0.64), indicating protection. Coinheritance of the SNPs was associated with further increase in the risk. Thus, the SNP genotypes in the three genes, present singly or as a coinherited panel constituted “Predictive Biomarkers” indicating increased risk of oral cancer in tobacco habitués.

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Abbreviations

SNP:

Single nucleotide polymorphisms

WT:

Wild type

HWE:

Hardy-Weinberg equilibrium

OR:

Odds ratio

CI:

Confidence interval

bp:

Base pair

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Acknowledgments

The authors gratefully acknowledge the support of Cancer Patients Aids Association (CPAA), Foundation of Medical Research (FMR), and Balabai Nanavati Hospital, Mumbai, India, for the project.

Role of the funding source

Funding was provided by the affiliated university for procurement of reagents for the project.

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Authors and Affiliations

  1. Department of Biological Sciences, Sunandan Divatia, School of Science, NMIMS (deemed-to-be) University, Vile Parle (West), Mumbai, Maharashtra, 400056, India

    Shaleen Multani & Dhananjaya Saranath

  2. Prince Aly Khan Hospital, Nesbit Road, Mazagaon, Mumbai, Maharashtra, 400010, India

    Sultan Pradhan

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  1. Shaleen Multani
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  2. Sultan Pradhan
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  3. Dhananjaya Saranath
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Correspondence to Dhananjaya Saranath.

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Ethics approval and consent to participate

The study was approved by the Institute Ethics Committees of NMIMS (deemed-to-be) University, Mumbai; Cancer Patients Aid Association, Mumbai; and Prince Aly Khan Hospital, Mumbai. All subjects gave written informed consent for voluntary participation in the study.

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ESM 1

Primer sequences for allelic discrimination PCR and sequencing primers. (DOCX 14 kb)

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Multani, S., Pradhan, S. & Saranath, D. Gene polymorphisms and oral cancer risk in tobacco habitués. Tumor Biol. 37, 6169–6176 (2016). https://doi.org/10.1007/s13277-015-4448-1

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  • DOI: https://doi.org/10.1007/s13277-015-4448-1

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