Tumor Biology

, Volume 37, Issue 5, pp 6169–6176 | Cite as

Gene polymorphisms and oral cancer risk in tobacco habitués

  • Shaleen Multani
  • Sultan Pradhan
  • Dhananjaya Saranath
Original Article


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, 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.


Oral cancer Single nucleotide polymorphism RASGRP3 GRIK2 PREX2 Increased risk 



Single nucleotide polymorphisms


Wild type


Hardy-Weinberg equilibrium


Odds ratio


Confidence interval


Base pair



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.

Compliance with ethical standards

Conflicts of interest


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.

Supplementary material

13277_2015_4448_MOESM1_ESM.docx (14 kb)
ESM 1 Primer sequences for allelic discrimination PCR and sequencing primers. (DOCX 14 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Shaleen Multani
    • 1
  • Sultan Pradhan
    • 2
  • Dhananjaya Saranath
    • 1
  1. 1.Department of Biological Sciences, Sunandan Divatia, School of ScienceNMIMS (deemed-to-be) UniversityMumbaiIndia
  2. 2.Prince Aly Khan HospitalMumbaiIndia

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