Skip to main content
SpringerLink
Log in

Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with oral cancer

  • Original Article
  • Published:
Oral Cancer

Abstract

Purpose

Oral squamous cell carcinoma (OSCC)—a subset of head and neck cancer is the sixth most common cancer worldwide and leading disease in India. The genes involved in PI3 K/AKT (Phosphatidylinositol 3-kinase—Akt) pathway, such as PIK3CA (Phosphoinositide-3-kinase catalytic α) and PTEN (Phosphatase and tensin homologue) were found to be associated with OSCC. The present study was aimed to find the genetic association of various polymorphisms in intron 9 of the PIK3CA gene and intron 5 of PTEN gene with primary OSCC tumors.

Methodology

50 OSCC patients for PIK3CA gene, 60 OSCC patients for PTEN gene and 72 healthy individuals were included in the study. PCR-direct sequencing analyzed the polymorphisms in intron 9 of PIK3CA and intron 5 of PTEN gene.

Results and conclusion

We observed rs114587137 (C>T) and rs17849071 (T>G) SNPs in intron 9 of the PIK3CA gene and rs35560700 (C>T) SNP in intron 5 of the PTEN gene. T allele of rs17849071 (T>G) was associated with the high-risk allele for developing OSCC; while G allele seemed to have the protective effect against OSCC (P = 0.02). We found an inverse association of rs17849071 (T>G) with OSCC development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

PIK3CA:

Phosphoinositide-3-kinase catalytic α

PTEN:

Phosphatase and tensin homologue

OSCC:

Oral squamous cell carcinoma

HNSCC:

Head and neck squamous cell carcinomas

SNP:

Single nucleotide polymorphism

References

  1. India Project Team of ICGC (2013) Mutational landscape of gingivobuccal oral squamous cell carcinoma reveals new recurrently mutated genes and molecular subgroups. Nat Commun 4:2873

    Article  Google Scholar 

  2. Anantharaman D, Chaubal PM, Kannan S, Bhisey RA, Mahimkar MB (2007) Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis 28(7):1455–1462

    Article  Google Scholar 

  3. Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  Google Scholar 

  4. Jayalekshmi PA, Gangadharan P, Akiba S et al (2011) Oral cavity cancer risk in relation to tobacco chewing, bidi smoking among men in Karunagappally, Kerala, India: Karunagappally cohort study. Cancer Sci 102:460–467

    Article  Google Scholar 

  5. Du L, Shen J, Weems A, Lu S-L (2012) Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. J Oncol 2012:1–12

    Article  Google Scholar 

  6. Molinolo AA, Amornphimoltham P, Squarize CH, Castilho RM, Patel V, Gutkind SJ (2009) Dysregulated molecular networks in head and neck carcinogenesis. Oral Oncol 45:324–334

    Article  Google Scholar 

  7. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22

    Article  Google Scholar 

  8. Kang S, Bader AG, Vogt PK (2005) Phosphatisidynositol 3 kinase mutations identified in human cancer are oncogenic. PNAS 102(3):802–807

    Article  Google Scholar 

  9. Qiu W, Schönleben F, Li X et al (2006) PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 12:1441–1446

    Article  Google Scholar 

  10. Ma Z et al (2013) Role of KAI1/CD82 polymorphisms in colon cancer risk in Han Chinese population. Med Oncol 30(3):668

    Article  Google Scholar 

  11. Xing JC, Tufano RP, Murugan AK, Liu D, Wand G et al (2012) Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with follicular thyroid cancer and PIK3CA amplification. PLoS One 7(11):e49192

    Article  Google Scholar 

  12. Liu P, Cheng H, Roberts TM et al (2009) Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8:627–644

    Article  Google Scholar 

  13. Collins F, Brooks L, Chakravarti A (1998) A DNA polymorphism discovery resource for research on human genetic variation. Genome Res 8(12):1229–1231

    Article  Google Scholar 

  14. Wang X, Tomso D, Liu X, Bell D (2005) Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes. Toxicol Appl Pharmacol 207(2):84–90

    Article  Google Scholar 

  15. Liu Z, Wei S, Ma H, Zhao M, Myers JN, Weber RS, Sturgis EM, Wei Q (2011) A functional variant at the miR-184 binding site in TNFAIP2 and risk of squamous cell carcinoma of the head and neck. Carcinogenesis 32(11):1668–1674

    Article  Google Scholar 

  16. Shah S, Shah S, Padh H, Kalia K (2015) Genetic alterations of the PIK3CA oncogene in human oral squamous cell carcinoma in an Indian population. Oral Surg Oral Med Oral Pathol Oral Radiol 120(5):628–635

    Article  Google Scholar 

  17. Kostakis GC, Papadogeorgakis N, Koumaki V, Kamakari S, Koumaki D, Alexandridis C (2010) Absence of hotspot mutations in exons 9 and 20 of the PIK3CA gene in human oral squamous cell carcinoma in the Greek population. Oral Surg Oral Med Oral Pathol Oral Radiol 109:53–58

    Article  Google Scholar 

  18. Tanwar R, Iyengar AR, Nagesh KS, Patil S, Subhash BV (2015) Prevalence of glutathione S-transferase M1 null polymorphism in tobacco users, oral leukoplakia and oral squamous cell carcinoma patients in South Indian population: a polymerase chain reaction study. Contemp Clin Dent 6(Suppl 1):S59–S64

    Article  Google Scholar 

  19. Kietthubthew S, Sriplung H, Au W, Ishida T (2006) Polymorphism in DNA repair genes and oral squamous cell carcinoma in Thailand. Int J Hyg Environ Health 209(1):21–29

    Article  Google Scholar 

  20. Tu H, Wu C, Kao S, Liu C, Liu T, Lui M (2007) Functional − 1562 C-to-T polymorphism in matrix metalloproteinase-9 (MMP-9) promoter is associated with the risk for oral squamous cell carcinoma in younger male areca users. J Oral Pathol Med 36(7):409–414

    Article  Google Scholar 

  21. Yen C, Liu S, Chen C, Tseng H, Chuang L, Yang C et al (2008) Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan. J Oral Pathol Med 37(5):271–277

    Article  Google Scholar 

  22. Dahia PM (2000) PTEN, a unique tumor suppressor gene. Endocr Relat Cancer 7:115–129

    Article  Google Scholar 

  23. Yamada KM, Araki M (2001) Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci 114:2375–2382

    PubMed  Google Scholar 

  24. Bu S, Asano Y, Bujor A, Highland K, Hant F, Trojanowska M (2010) Dihydrosphingosine 1-phosphate has a potent antifibrotic effect in scleroderma fibroblasts via normalization of phosphatase and tensin homolog levels. Arthritis Rheum 62:2117–2126

    PubMed  PubMed Central  Google Scholar 

  25. Hao LS, Zhang XL, An JY, Karlin J, Tian XP, Dun ZN, Xie SR, Chen S (2009) PTEN expression is down-regulated in liver tissues of rats with hepatic fibrosis induced by biliary stenosis. APMIS 117:681–691

    Article  Google Scholar 

  26. Kato M, Putta S, Wang M, Yuan H, Lanting L, Nair I, Gunn A, Nakagawa Y, Shimano H, Todorov I, Rossi JJ, Natarajan R (2009) TGF beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol 11:881–889

    Article  Google Scholar 

  27. Xia H, Diebold D, Nho R, Perlman D, Kleidon J, Kahm J, Avdulov S, Peterson M, Nerva J, Bitterman P, Henke C (2008) Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis. J Exp Med 205:1659–1672

    Article  Google Scholar 

  28. Kuwano K (2006) PTEN as a new agent in the fight against fibrogenesis. Am J Respir Crit Care Med 173:5–6

    Article  Google Scholar 

  29. Teunissen BE, Smeets PJ, Willemsen PH, De Windt LJ, Van der Vusse GJ, Van Bilsen M (2007) Activation of PPAR delta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Cardiovasc Res 75:519–529

    Article  Google Scholar 

  30. Shah S, Jajal D, Mishra G, Kalia K (2017) Genetic profile of PTEN gene in Indian oral squamous cell carcinoma primary tumors. J Oral Pathol Med 46(2):106–111

    Article  Google Scholar 

Download references

Acknowledgements

We acknowledge the Dean and medical staff of the Pramukh Swami Medical College and Hospital, Karamsad, for the collection of cancerous as well as healthy tissues for the present study. Sejal Shah has been awarded as a woman scientist in this project.

Funding

Department of Science and Technology, Women Scientist Scheme-A, New Delhi, India. Sanction no: -SR/WOS-A/LS/511/2011-G dated on 24/5/2012.

Author information

Author notes

  1. Kiran Kalia

    Present address: National Institute of Pharmaceuticals Education and Research (NIPER) Ahmedabad, Opposite Air Force Station, Palaj, Gandhinagar, Gujarat, 382355, India

Authors and Affiliations

  1. Lab #103 B, BRD School of Biosciences, Sardar Patel University, Vallabh Vidhyanagar, Gujarat, 388 120, India

    Sejal Shah & Kiran Kalia

  2. Otolaryngologist and Head and Neck Surgeon, E N T Department, P. S. Medical College, Karamsad, Gujarat, 388325, India

    Girish Mishra

  3. Department of Microbiology, School of Science, RK University, Rajkot, India

    Sejal Shah

Authors
  1. Sejal Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Girish Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kiran Kalia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kiran Kalia.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shah, S., Mishra, G. & Kalia, K. Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with oral cancer. Oral Cancer 2, 83–89 (2018). https://doi.org/10.1007/s41548-018-0012-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41548-018-0012-1

Keywords

Search

Navigation