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Impacts of TNF-LTA SNPs/Haplotypes and Lifestyle Factors on Oral Carcinoma in an Indian Population

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Abstract

Background and Objectives

To investigate a potential association between single-nucleotide polymorphisms (SNPs) and  haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population.

Materials and Methods

In this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., −238G/A, −308G/A, −857C/T, −863C/A, −1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction–restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples.

Results

The allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls.

Conclusion

Five SNPs at the TNF-LTA locus (i.e., −308G>A, −857C>T, −863C>A, −1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.

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Acknowledgments

We gratefully acknowledge our patients, their relatives, and clinicians for their support and cooperation.

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Author notes

    Authors and Affiliations

    1. Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India

      Kapil Bandil, Pallavi Singhal, Upma Sharma, Showket Hussain & Mausumi Bharadwaj

    2. Barasat Cancer Hospital, Kolkata, India

      Surojit Basu

    3. Division of Molecular Immunology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India

      Aditya Parashari

    4. Division of Clinical Oncology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India

      Veena Singh

    5. Division of Epidemiology and Biostatistics, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India

      Ashok Sehgal

    6. Department of Oral Pathology, Institute of Technology and Science, Greater Noida, India

      Animesh Shivam & Puneet Ahuja

    7. Department of Biochemistry, University College of Medical Sciences, University of Delhi Dilshad Graden, Delhi-65, India

      Basu Dev Banerjee

    8. Division of Cytopathology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India

      Ravi Mehrotra

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    1. Kapil Bandil
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    Correspondence to Mausumi Bharadwaj.

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    Conflict of interest

    KB, PS, US, SH, SB, AP, VS, AS, AS, PA, MB, BDB, and RM have no conflict of interest to report.

    Funding

    This study was funded by grant no. DST SR/SO/HS/0041/2011 from the Government of India to MB and core funds from ICPO (ICMR), Noida, India.

    Ethical approval and informed consent

    The study procedures were approved by the institutional ethical committee (approval no. ICPO/IEC/P-003/2011), Noida, India. Informed consent was obtained from all participating individuals.

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    K. Bandil and P. Singhal contributed equally to this work.

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    Bandil, K., Singhal, P., Sharma, U. et al. Impacts of TNF-LTA SNPs/Haplotypes and Lifestyle Factors on Oral Carcinoma in an Indian Population. Mol Diagn Ther 20, 469–480 (2016). https://doi.org/10.1007/s40291-016-0215-2

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